FAQs

 

 


Screening

Q: In the very rare situation when an acute stroke patient is anticipated to require plasma exchange therapy during the first 3 days post stroke, what would the expected impact be on the glucose levels and insulin treatment? 
A: During plasma exchange (PLEX) therapy, it is believed that some insulin dissolved in the plasma portion of blood is removed and dextrose is typically added.  Both of these would interfere with blood glucose regulation by the SHINE protocol in both treatment groups. For this reason, patients expecting to receive PLEX during the first 3 days post-stroke should not be enrolled in the SHINE trial. If a patient is enrolled in SHINE and requires PLEX therapy during the treatment period, given the potential interference of the therapy on glucose regulation, contact the study hotline to discuss the safety of continuing on the treatment protocol.

Q: We are screening a patient who meets all inclusion criteria.  However, there is concern that the patient appears to be very insulin resistant and if they are enrolled in the control group, we are concerned about crossing the safety boundary of glucose >500 mg/dL.  How should we proceed? 
A: Sites should use clinical judgment and consult with the local treating team to decide how best to proceed.  Please keep in mind that, in the control group, all patients start at Level 1 for the first 24 hours from randomization.  This means that the maximum SQ insulin dose per the sliding scale during Day 1 is 32 units based on the patient’s blood sugar level. Once enrolled, a call to the study hotline is required for any glucose level of 500 or greater.  As always, the SHINE PI line is available for all eligibility questions.

Q: Does the time of randomization or the time that the study infusion is started apply when considering the 12 hour rule from symptom onset for SHINE eligibility?
A
: All study patients must be randomized within 12 hours of symptom onset or last known well.  As a reminder, 3 CRFs – Eligibility, NIHSS and Randomization must be completed in order to randomize.  If the time from symptom onset or last known well is greater than 12 hours from the time that the final CRF, the Randomization CRF, is submitted in WebDCU, randomization will be blocked.  Treatment should be started as soon as possible after randomization.   Whereas emergency randomization is available in case of system technical difficulties within 12 hours of onset, no emergency or alternative randomization is allowed after the 12 hours from onset.

Q: Our site is on temporary enrollment suspension due to a lapse in our IRB approval.  Should we still continue to enter Screen Fail Log data into WebDCU?
A
: We would strongly recommend that your site continues to screen during the period of enrollment suspension; however, it is not required that these are entered in WebDCU in cases where a site’s status has been changed to Enrollment Suspended.  The screen fail logs are posted in WebDCU on the first day of each month for each active site.  If your site is not actively enrolling on the first day of the month, the screen fail log for that month will not post.  Again, we would recommend that you screen and maintain documentation at your site but not expect to enter in WebDCU during the period of suspended enrollment.

Q: Are patients with an insulin pump eligible for SHINE?  We are screening a patient and don’t see a specific exclusion for insulin pumps.
A: It is possible but highly unlikely that a patient with an insulin pump will be eligible for the SHINE trial.  If you are considering eligibility for a patient that requires an insulin pump, consider the following:

  1. Confirm that the patient has type 2 diabetes.  Most insulin pump patients have type 1 diabetes.  It is possible but rare that a patient could require a pump for management of type 2 diabetes.
  2. Consider the current average daily insulin requirement for the patient when healthy.  Consider whether the control treatment protocol with maximum of 32 units of regular insulin for the first 24 hours is reasonable (this would require glucose checks over 450 at each check to get the maximum of 8 units for each of 4 dosing times).  If the patient is currently requiring over 32 units a day, then this is likely not a good candidate for SHINE.  For patients requiring less than 32 units a day, consider that the pump will need to be turned off for the duration of the treatment period, and that if in the control group, glucose levels will be treated based on the study sliding scale.  Level changes may occur to allow for more aggressive glucose management, but these occur only at 24 and 48 hours from time of randomization.
  3. Questions about insulin requirement and glucose levels at the time of screening can be directed to the SHINE study hotline (800-915-7320)

Q: The protocol indicates that Type I diabetics are being excluded due to insulin use. Shouldn’t Type II insulin dependent diabetics be excluded as well?
A: During the stress of hospitalization, type 1 diabetics and pregnant women routinely require IV insulin.  Type 2 diabetics who are insulin dependent may be enrolled in the study.  It will be per the discretion of the enrolling investigator to determine if the potential subject is one that could be safely randomized to either treatment group.

Q: I can’t remember if we came to resolution regarding a physician investigator being present for enrollment of subjects.  ALIAS requires a physician investigator to be physically present during enrollment, POINT requires a phone call to a physician investigator prior to randomization and ProTECT requires neither.  Where does SHINE fall in this?
A: Enrollment will be overseen by an enrolling investigator as designated on the site Delegation of Authority Log.  Any study team member who has been delegated the responsibility to perform all of the functions required to oversee enrollment on the DOA log and is certified to do the assessments required during this visit can be an enrolling investigator.  This person does not have to be licensed.

Q: Can we use the glucose check from the EMS for eligibility?
A: You will need one POC glucose check (finger stick) at the enrolling hospital.  This must be a POC glucose check using capillary blood and cannot be a serum glucose level from the lab.  Values from the EMS or the transferring hospital cannot be used to confirm eligibility and randomize.  After the first check at the hospital where the patient will be enrolled, if the patient is eligible, another POC is not required prior to randomization.  However, if the first check made the patient eligible and another check was done and is not in range, the patient is no longer eligible and should not be randomized. 

If the BG is below the eligible level <110 for patients with known type 2 diabetes or <150 for patients without a diagnosis of type 2 diabetes on admission, you can choose to repeat.

Q: How do you score the pre-stroke mRS for eligibility?
A: If the patient had a stroke before the currently acute stroke, score zero only if all signs and symptoms from that stroke have resolved. If all signs and symptoms from that stroke have resolved, the patient must also be able to live independently and walk without assistance.  Necessary devices for walking are not considered assistance.

If the patient has never had a stroke before, in order to score 0, s/he must have been capable of living independently and walking without assistance. Again, necessary devices for walking are not considered assistance.

Sample mRS cases are available on the SHINE study website to help your study team become familiar with scoring the pre-stroke modified Rankin.

Q: How do we distinguish between Type 1 and Type 2 diabetes when we are trying to determine if a patient meets eligibility criteria to be enrolled?
A: About 25 million children and adults in the United States (8.3% of the population) have diabetes. Type 2 is the most common form of diabetes. Approximately 95% of all diabetes in the United States have Type 2 diabetes, while only approximately 5% of people with diabetes have Type 1 diabetes.

Type 1 (also called T1DM, insulin-dependent or juvenile diabetes)
Type 1 diabetes (T1DM) can occur at any age but most commonly is diagnosed from infancy to the late 30s. In this type of diabetes, a person's pancreas produces little or no insulin. T1DM occurs when the immune system attacks and destroys the insulin-producing cells in the pancreas. Its onset has nothing to do with diet or lifestyle. There is nothing you can do to prevent T1DM, and at present nothing you can do to get rid of it. Type 1 diabetes causes dependence on injected or pumped insulin for life.

Type 2 (also called T2DM, non-insulin-dependent or adult-onset diabetes)
Type 2 diabetes is the most common form of diabetes. Type 2 diabetes typically develops after age 40, but can appear earlier, and has recently begun to appear with more frequency in children. In this form of diabetes, the pancreas still produces insulin, but the body does not produce enough or is not able to use it effectively. Treatment includes diet control, exercise, self-monitoring of blood glucose and, in some cases, oral drugs or insulin.
Determination of Type 1 versus Type 2 DM should be based on history provided by patient and family and medical records or physician contact. If unknown if Type 1 or Type 2 DM, any patient on insulin therapy with no known history of oral agents for treatment of diabetes will be assumed to be Type 1.

The following questions may help you discern the diagnosis:
-Has your doctor ever tried to control your diabetes with diet or exercise only? [If yes, the patient will be assumed to have Type 2 DM.]
-Have you ever taken a pill for your diabetes? [If yes, the patient will be assumed to have Type 2 DM.]
-Since your doctor told you that you have diabetes, have you always used insulin shots or an insulin pump to control your blood sugar? [In combination with other questions, this will help to identify patient with Type 1 diabetes since they always require insulin.]
-How old were you when you found out that you have diabetes? [In combination with other questions, this will help to identify patient with Type 1 diabetes since they are most commonly diagnosed from infancy to late 30s.]

Please contact the PI on call if you have questions about the determination of Type 1 versus Type 2 DM.

Q: What do we do when a patient says he has borderline diabetes?
A: To be eligible for SHINE, a patient must either have a history of type 2 diabetes and a glucose level of >110mg/dL OR a glucose level of >150mg/dL with no known history of diabetes.  For the purpose of study eligibility, the information that is used to determine a diagnosis of diabetes is medical history provided by the patient and family and/or the medical record.  If a patient or the family reports a history of borderline diabetes and it is not clear in the medical record, contact the PI on call.  The PI on call will work with the study team to make a determination about whether that patient has a history of diabetes.

Q: We have a patient who is otherwise eligible but has had a renal transplant. Is that a reason for exclusion from the study?
A: A history of a renal transplant is NOT a reason to exclude a patient from the study.  If there is a patient that is being screened for SHINE with a history of renal transplant, consider the eligibility criteria carefully (e.g. serious conditions which make the patient unlikely to survive 90 days, is again on renal dialysis, etc.), and as long as otherwise eligible, renal transplant alone is not a reason to exclude.

Q: We’re screening a patient who was given D50 in the ambulance.  It has been over two hours since he arrived, and his glucose is 224 mg/dL.  Is he automatically excluded because of the D50?
A: No, a patient is not automatically excluded.  If a study team is screening a potential SHINE subject who is known to have received dextrose, contact the PI on call.

Q: Can a patient who has gotten insulin in the ED be enrolled?
A: Yes, many of the patients who will be enrolled in the trial will be known to have type 2 diabetes and may be on home insulin or could in some cases receive non-study diabetes treatment medications prior to the study team being involved.  The most recent finger stick point of care glucose at the time of randomization will be used to confirm eligibility and must have been checked after the insulin was given.  The glucose must be >110mg/dL in patients with type 2 diabetes or ≥150 mg/dL in patients without diabetes.  Once enrolled in SHINE, no other diabetes treatment medications (i.e., oral agents, IV or subcutaneous insulin) besides the assigned protocol treatment will be allowed during the 72-hour treatment period because such medications would confound the study.

Q: Can a patient with an in-hospital stroke be enrolled in SHINE?
A: Yes, patients with an in-hospital stroke should be screened for SHINE.  Randomization must occur within 12 hours of symptom onset.  The date and time of hospital arrival should be documented on the Eligibility CRF. Contact the PI on call for questions about assessing the pre-stroke mRS for patients who have had an in-hospital stroke.

Q:  We are screening a potential SHINE candidate who was diabetic and on medication several years ago.  Now with diet and exercise, he is off all medication and has a normal HbA1c. Does this count as having a diagnosis of diabetes?
A: For the purposes of the SHINE trial, these patients should be considered ‘non-diabetic’ and only eligible with a glucose level >150mg/dL.  Just as someone with gestational diabetes had a diagnosis in the past and is at risk of again developing diabetes, these patients should not be considered to have a current diagnosis of T2DM.

Q: What are the reasons that a patient who is being considered for SHINE would be excluded due to the inability to obtain a full NIHSS?
A: When it is not possible to obtain a full NIHSS within 30 minutes of the time of randomization, potential candidates must be excluded from SHINE.  Categories on the NIHSS may be untestable due to joint fusion or amputation at the proximal joint or due to intubation or other barriers to producing speech. 

In the case of amputation or joint fusion at the shoulder or hip, motor arm, motor leg and the limb ataxia assessments are untestable. Note that only amputation or joint fusion at the proximal joint are untestable.

If a patient is intubated or has other physical barriers to producing speech, it is likely not possible to assess dysarthria within 30 minutes of the time of randomization.  Also note that it is possible score a comatose patient by using coma scoring instructions.

Q: We are evaluating a patient who presented to ED and has never had a stroke but uses a wheelchair.  How do we score pre-stroke mRS because of the wheelchair?
A: To be eligible for SHINE, patients who have never had a stroke must have a pre-stroke mRS of 0 and must be able to live independently and walk without assistance. Although some people who are unable to walk use a wheelchair and are able to live independently, they should not be enrolled in SHINE because by strict mRS definition they will have an mRS >3 at 3 months. Thus, such patients cannot achieve our predefined favorable outcome.

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Intervention

Q: GlucoStabilizer is recommending that we continue to do Q1 hour glucose checks for our intervention patient who has not been requiring insulin for nearly 24 hours.  How should we manage this? 
A
: In the rare situation that blood glucose levels remain in target (80-130mg/dL) for an intervention patient without any IV insulin, call the SHINE study hotline at 800-915-7320.  GlucoStabilizer will continue to recommend hourly checks when the administered insulin infusion rate is 0.  The PI on call is able to work with your team to consider options for managing the treatment protocol.

Q: What is the dose for the subcutaneous saline injections?  Our nurses said they do not have a syringe small enough to measure .05mL, and the insulin syringe doesn’t measure in mLs.
A
: The subcutaneous saline injection is 0.05mL, which is the equivalent of 5 units in an insulin syringe.  SQ saline should be given only to patients in the intervention group who are NPO or on continuous tube feeds and should be administered at the time of the glucose check closest to 09:00 and 21:00.

Q: How many carbohydrates do you enter if an intervention patient ate about a quarter of a meal?
A
: For patients who are cleared for a PO diet, a 60 grams/meal carbohydrate diet will be ordered for breakfast, lunch and dinner as part of standard care.  Dietary teams should be involved in assuring that the 60 grams/meal carbohydrate diets are maintained throughout the study protocol.  For patients in the intervention group, about twenty minutes after the initiation of a meal, the clinical nurse should assess meal consumption.  If the patient is not finished eating, an assessment of the likely total consumption is required.

The nurse will estimate the proportion of the meal consumed by the patient.  This estimate is based on the entire meal irrespective of its subparts or food groups:

  1. Full or near full consumption à 60 grams carbohydrates
  2. No or nearly no consumption à 0 grams carbohydrates
  3. Partial consumption à30 grams carbohydrates

Note that only 30 or 60 must be entered into GlucoStabilizer.  Zero (0) must not be entered as this will change the timing of the next glucose check).  GlucoStabilizer will allow entry of values other than 30 or 60, but this will result in meal insulin dosing error which is a protocol deviation.  Clinical nurses and study teams should be trained that the estimated carbohydrates consumed must only be entered in GlucoStabilizer if 60 grams or 30 grams.  Again, if no or nearly no consumption is estimated, no meal insulin (carb coverage) is required.  Because no meal insulin is required, no entry in GlucoStabilizer should be made, and no injection is given.

In this example, the nurse would need to decide whether the patient ate none or nearly none of the meal or if there was partial consumption of the meal (if described as a quarter of the meal, this is likely to be estimated as partial consumption).  If partial consumption, 30 grams would be entered in the Cover Carbs function of GlucoStabilizer.

Q: How do you resume a drip in GlucoStabilizer?
A
: When the SHINE intervention treatment is temporarily interrupted for any reason (e.g. patient needing to go off the care unit and the clinical nurse cannot accompany the patient to maintain the SHINE study procedures), the IV insulin drip should be stopped and the Stop/Hold function should be selected in GlucoStabilizer.  If it has been <3 hours when the study team is ready to restart the infusion, the protocol specifies that the drip should be resumed.

To resume a drip, confirm that it has been less than 3 hours since the drip was stopped.  If <3 hours, click on the Resume button in GlucoStabilizer.  A table will display with Run No., SHINE Subject ID, Date and Time.  It is important that you carefully review each row in the table to be certain that you select the most recent drip run for the correct SHINE subject.  Once confirmed, put the cursor in that row and choose Select.  You will be prompted to confirm the patient information (which is greyed out and does not display any patient identifiers) and then will select No to the option to Change to advanced settings.  The GlucoStabilizer main screen will display, picking up where things were left off when the drip was stopped. 

Since GlucoStabilizer continues to count down to the next check even when the Stop/Hold option is selected, it is possible that a glucose check will be due and the alerts will be flashing and audible. 

Instructions with screenshots for returning to the study protocol (Starting a new drip or Resuming) after a pause in study treatment and a short slide set are posted on the study website.

Q: Our pharmacy has asked for the range of dosage (# of units of insulin) for the intervention group for the study orders. Can you please provide?
A
: The GlucoStabilizer calculations for the insulin infusion, meal insulin and D50 follow.
Regular insulin infusion: There is not a hard maximum cutoff to the IV regular insulin dosage recommentation. The recommendation is calculated based on the formula "(BG-60) * multiplier". However, if the insulin dose is > 32, a warning message is displayed to check with the physician before proceeding.

For the rapid acting analog (meal) insulin dosing, the insulin to carbohydrate ratio is 1:15. One unit of insulin will be recommended for every 15 grams of carbs consumed. Based on the study protocol diet and instructions for estimating consumption, carbohydrate intake per meal will be estimated to be either 30 or 60 grams. Two units of rapid acting analog insulin will be recommended for patients that partially consume the meal (entry of 30 into Cover Carbs option in GlucoStabilizer). Four units of SQ rapid acting analog insulin will be recommended for patients that consume all or nearly all of the meal (entry of 60 into Cover Carbs option in GlucoStabilizer). If none or nearly none of the meal is consumed, there should be no entry in GlucoStabilizer, and no rapid acting analog insulin given for that meal.

For dextrose 50% in Water (D50), when the BG < 80mg/dL, an individualized dose is calculated per GlucoStabilizer based on the following formula: (100-BG) * 0.4
The lowest value that is allowed for the BG is 1, so the highest theoretical value for D50 in the intervention group is (100-1) * 0.4 = 40mL
(As a reminder in the control group, IV D50 25mL (1/2 amp D50) will be given every 15 minutes when the BG < 80mg/dL).

Q: Should meal insulin be given if a study patient was hypoglycemic at the beginning of the meal?
A
: When the blood glucose is < 80mg/dL, the hypoglycemia prevention and management protocol indicates that the insulin infusion should be stopped and all subcutaneous insulin injections should be held. Any time that any portion of the meal occurs at the same time that the BG < 80mg/dL and the hypoglycemia protocol has been initiated, the meal insulin should not be administered for that meal. An example of the way that this could occur is that if a glucose check happens to be due at the same time the meal is delivered. If the glucose is < 80mg/dL, the hypoglycemia protocol will be initiated. If the patient starts eating while the glucose is known to be < 80mg/dL, no meal insulin should be given.

Because no meal insulin should be administered, no entry in GlucoStabilizer should be made, and no injection is given. Consumption should be documented on the study CRF (Form 20: Daily Care Log). The questions, 'Was meal insulin given?' should be answered "No", and the reason should be listed as "Other". Specify that the reason that no meal insulin was given and "Other" was selected was due to the "Hypoglycemia protocol".

The D50 should alsways be given per the recommendation of GlucoStabilizer - even if the patient is just starting to eat at the same time. Questions about the hypoglycemia protocol and meal insulin dosing can be directed to the SHINE PI on call, and concerns about safety should be directed to the Independent Safety Monitor.

Q: Is it possible for us to get a copy of the GlucoStabilizer dosing data that the nurses have entered for each patient?
A
: Yes. The history for each study patient can be downloaded and is available in GlucoStabilizer for 48 hours after the last entry. Instructions with screenshots are posted on the study website.

Q: Can you clarify the requirements for SHINE for the source of blood for glucose testing? (UPDATED 9-4-14)
A
: Due to known variations in blood glucose levels between capillary, venous and arterial sources, trial procedures have been updated to clarify the recommended blood source used for study point of care (POC) glucose testing.   Capillary blood is the required source for the enrollment POC glucose test to determine eligibility. Capillary blood remains the preferred source of blood for POC glucose testing throughout the trial. 

When there are concerns about the number of finger stick checks or withdrawing consent for SHINE treatment, switching to venous blood samples for the remainder of the treatment period will be permitted. When there is a choice of multiple veins, the vein closest to a hand should be used to obtain the samples. Once venous blood becomes the source of glucose checks, venous blood should remain the source for the remainder of the treatment period.  In rare occasions when venous blood cannot be reliably obtained, arterial blood may be used for SHINE POC glucose measurements. Again, once arterial blood becomes the source of glucose checks, arterial blood should remain the source for the rest of the treatment period.  If the patient will not have arterial access for the remainder of the treatment period, arterial blood should not be used. 

If clarification is needed, site study teams are encouraged to call the SHINE PI hotline.

Q: We had a study patient in the intervention group who required very frequent glucose checks during the treatment period. Can we use blood from the IV if they are drawing other labs?
A
: The blood glucose monitoring language has been updated in the MOP to include an exception to requiring capillary blood for the POC testing.  Blood glucose will be monitored using point of care finger stick glucose checks.  Exceptions to allow blood draws from a patient line to be used for POC testing may be considered in the following situations:
1) when the number of finger stick glucose checks exceeds the maximum expected number daily as listed in the consent, or
2) if the patient or family express concern about continued study participation due to the number of finger stick checks.
Even when non-capillary blood is used for glucose testing, the method must continue to be point of care.

Q: What do we do if the glucose check is due at the same time we're getting ready to enter the carb coverage in GlucoStabilizer?
A
: When you make an entry in the ‘Cover Carbs’ function in GlucoStabilizer, the timing of the next check is automatically pushed out to 1 hour later (even if the clock has been counting down and a glucose check is almost due).  If a glucose check is almost due and you enter the carb consumption, you will not be prompted to check the glucose for another hour.  If you have a patient who is on the q2 hour schedule for checks, this means that it could be nearly 3 hours between glucose checks.  Because we want to avoid this, clinical nurses are encouraged to use the +/-15 minute window for glucose checks to ensure that a check is done at the time that it is due.  If the clock is counting down and the meal has arrived, make every effort to hold the meal until the glucose check is due (+/-15 minutes).  Once you have entered the glucose and received the insulin infusion rate recommendation, the patient can begin the meal.  This will help to avoid a gap in glucose checks.

Q: We entered the estimated carb consumption in GlucoStabilizer and received a dose recommendation for the meal insulin; however, a few minutes passed between the time that the box popped up and we received the recommended rate and trying to enter the accepted dose given – and the screen disappeared.  What should we do when this happens?
A
: GlucoStabilizer will not document that a meal insulin dose has been given unless the nurse initials are entered and the carbs and recommended dose are confirmed.  If you begin to enter the carb consumption and receive a dose recommendation – but it times out while you are administering the dose (and the pop-up for confirmation disappears) - you will need to re-select Cover Carbs and enter the grams consumed (30 or 60) to again receive the dose recommendation.  The meal insulin dosing is based on consumption and will not change (either 2 units if 30 grams were consumed or 4 units if 60 grams were consumed).  However in order for this to be documented in the study laptop, it must be entered and confirmed using the Cover Carbs function.

Q: We have a patient who is on day 1 in the intervention arm. He went to MRI last night, and the imaging shows a brain tumor and no DWI lesion. What do we do?
A
: When there is a change in diagnosis from acute cerebral ischemia (stroke or TIA), all study treatments must be stopped. The reason for stopping must be documented in the medical record and study laptop. As with any transition when the patient is not ready for discharge but the study treatment must be stopped, initiate site standard care for glucose control. In WebDCU, complete End of Treatment Visit and document the stroke mimic with narrative. Continue to follow the patient per protocol, but off study treatment (6-week and 3-month follow-up visits).

Q: We have a patient in the intervention arm and just did a glucose check.  GlucoStabilizer is recommending that the insulin infusion rate is decreased to 0.3 u/hr.  The pump doesn’t go any lower than 0.5 u/hr.
A
: In any case when the GlucoStabilizer recommendation is lower than the lowest infusion rate of the pump, decline the recommendation.  Enter 0 for the infusion rate when confirming the blood glucose and administration rate.  Turn off the drip and document that the infusion was stopped in the medical record.  The GlucoStabilizer will continue to count down to next check, and the visible alert will appear and the audible alert will sound when the glucose check is due.  Check the glucose, enter and re-enter the value, and if the recommended rate is one that your infusion pump can accommodate, restart the infusion at that rate.  If the recommended rate continues to be lower than the lowest rate for your infusion pump, repeat the steps above to decline the recommendation and check again per GlucoStabilizer. 

Q: We enrolled a patient who was cleared for a PO diet as soon as she was admitted to the stroke unit. At each meal, however, she has eaten none or nearly none of the food on the tray.  Do we need to be giving her the SQ saline injections at 09:00 and 21:00 since she is not eating?
A
: SQ saline should only be ordered for patients who are NPO or on continuous tube feeds.  SQ meal insulin should be ordered for patients who have been cleared for a PO diet or are on bolus tube feeds.  If a patient is cleared to eat but is not eating, do NOT give SQ saline.  The decision about which SQ study treatment is appropriate in the intervention group should be based on the active diet order. 

Q: Our subject in the intervention group had a worrisome hypoglycemia of 49 mg/dL, which corrected with D50. Is there anything that we can do to help avoid additional episodes of hypoglycemia? (NEW 7-19-16)
A: Perhaps yes. Sometimes a reason can be identified, such as errors in insulin dosing (too much), taking non-study antidiabetic medications by mistake, sneaking in high sugar snacks that can mislead the Glucostabilizer program into recommending too much insulin, or a change in medical status that can affect insulin sensitivity (e.g. infection). Consider whether any protocol deviations occurred as they can be corrected. Call the SHINE hotline for instructions on hypoglycemia related to protocol deviations (might be best to start a new drip). Also, some patients on the Glucostabilizer protocol occasionally do have recurrent hypoglycemia episodes (<70 mg/dL) for no apparent reason. Remember to call the SHINE hotline for 3 episodes of hypoglycemia (<70 mg/dL) within any 24 hour period, or for a single measurement of <40 mg/dL.

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Control

Q: We have a patient in the control group and started study treatment.  It has been less than an hour, and we need to pause for MRI.  How do we manage pauses in the control group during the hourly checks?
A
: When the SHINE control group treatment protocol is temporarily interrupted for any reason, the IV saline drip should be stopped.
Upon return, if hourly glucose checks or SQ insulin injections were not missed, maintain the schedule for glucose checks and dosing.  Resume IV saline infusion at the next hourly glucose check and continue checks as scheduled.
If hourly glucose checks were MISSED, immediately check the POC glucose upon return and use the result to resume the IV saline.  If a SQ insulin dosing time was missed, use the result to give SQ insulin per the sliding scale immediately.  Repeat checks every hour from the time of the check to resume for a total (including the time before the pause) of four hours of hourly checks and then transition to the schedule for Q3 hour checks.
Call the PI on call (800-915-7320) with questions about timing of the glucose checks or pausing in the control group.

Q: If we have a patient enrolled into the control group at around 01:00, 02:00, etc., we know we have to start and adjust the saline infusion with each hourly glucose check, but when can we give the patient their SQ insulin?  The instructions say to only give SQ insulin at 6:00, 12:00, 18:00 and 24:00.
A
: It is possible that a patient randomized to the control group could be started on the protocol but not receive a subcutaneous insulin injection for several hours.  During the first four hours after the study infusion has been started, the glucose will be checked and the saline infusion rate adjusted if indicated each hour.  The SQ insulin dosing times are 06:00, 12:00, 18:00 and 24:00.  If a q1 hour check is within 30 minutes of the next dosing time, the SQ insulin dose should be given at that time (slightly early) so that the dose is NOT missed (i.e. If one of the hourly checks is at 11:38, give the SQ insulin dose at this time since it is within 30 minutes of the noon dosing time).  Subcutaneous insulin must only be administered during the hourly checks if it is within 30 minutes of one of the scheduled SQ insulin dosing times.

Q: Does the Control group also have audible alerts to check glucoses? Or only the Intervention group?
A
: The control treatment screen is a static screen designed to mimic a paper sliding scale protocol.  The laptops also allow the study team to capture glucose values and study treatment administration.  There are no automated visual or auditory alerts in the control group.  Sites are recommended to use mechanisms that are already in place for clinical care at their institution to remind nurses of the glucose checks and study treatment dosing times. 

For example, if a site uses an EMR with a dosing schedule and late dose reminders, the same system might be effective for reminder nurses to follow the SHINE study protocol.

Q: When does the time start for the hourly glucose checks in the control group – the start of the 72 hour treatment period/randomization or when the study infusion is started?
A
: The timing of the hourly glucose checks is based off of the start of the study infusion.  Once the IV infusion is ready to be started, check the finger stick point of care glucose even if it has been checked before (BG must be tested immediately prior to starting infusion). This is the time that should be used to calculate when each of the 4 hourly checks should happen. 

For example, if the study infusion is started at 11:50, the first of the four hourly checks should happen at 12:50 (+/-15 minutes).  The subsequent hourly checks will be due at 13:50, 14:50 and 15:50.  After the four hourly checks, transition to the q3 hour schedule for glucose checks 03:00, 06:00, 09:00, 12:00, 15:00, 18:00, 21:00 and 24:00.  In this example, the first q3 hour check would be due at 18:00.

Q: If a control patient has advanced to Level 2 but is mistakenly dosed off of Level 1, what do you do?
A
: Every effort should be made to ensure that the clinical nurses use the correct column for the levels in the sliding scale table so that dosing is per the study protocol.  In the event that the clinical nurse or study team becomes aware that the dose given was less than what was indicated per the sliding scale and it is outside of the window for the check/SQ dosing, the dose should not be corrected.
Concerns about the protocol and dosing errors can always be directed to the SHINE principal investigator on call (800-915-7320 ext. 1).  If there is a patient safety concern due to the dosing error, the independent safety monitor can be reached at 800-915-7320 ext. 2.
Errors in study treatment dosing must be reported to your IRB per institutional reporting requirements. 

Q: If a patient advances to Level 3 and had been given the wrong dose of SQ insulin during the previous 24 hours, how do you calculate the basal insulin (Lantus/glargine) dose?
A: Per the study protocol, the dose of basal insulin is 40% of the total subcutaneous insulin given in the previous 24 hours. The dose should be calculated based on the SQ insulin given rather than the total SQ insulin required (based on glucose values and corresponding sliding scale insulin doses).

Q. What do we do when the glucose is high or even very high at a glucose check in the control group that does not require dosing (such as 3AM, 9AM)?
A
: If the glucose is over 500mg/dL at any check, you must contact the independent safety monitor on the SHINE study hotline for a recommendation (800-915-7320 ext. 2).  If at any time the treating team feels there is a known condition that has declared itself that requires different treatment from the protocol (such as DKA or hyperosmolar coma) then the treating team can withdraw study treatment but keep the patient in the study for follow up.

If the glucose is higher than target (even if substantially higher than target), the patient should be treated per the protocol. Remember that control group patients that have higher insulin needs will be escalated to level 2 and or level 3 if there need is sustained. Giving additional insulin puts patients at risk for hypoglycemia because the protocol is geared to escalate. Avoiding hypoglycemia is of most importance.

The DSMB and the SHINE protocol monitoring committee are overseeing the success of the protocols and will recommend adjustments in the protocols if necessary.

Q: How do I document when we stop the saline infusion in the study laptop?
A
: If the saline infusion needs to be stopped for a pause in the protocol or at the end of the treatment period, the rate change should be documented in the study laptop.  Select New Event on the Control Treatment Screen, adjusting the time if necessary to reflect the time that the saline infusion was actually stopped.  The computer will not allow an entry of 0 or a blank for the glucose value, so we are recommending that you enter the previously collected glucose level.  The saline infusion rate should be 0 as well as all other remaining fields in the entry screen.  In the notes section, document that the glucose level was from the previous check (do NOT check the glucose just for this purpose) and that the infusion was stopped. 

If it is later necessary to restart, enter the SHINE Subject ID in the Control Treatment Screen to access the previously entered study data, and follow the instructions for pausing in the MOP to return to the study protocol.  (For example, the glucose is 189mg/dL at 03:06 scheduled check, the IV Saline=4mL/hr, SQ insulin=0 units, Glargine=0 units and D50=0mL.  At 04:45, if you need to pause the protocol, document the previously entered glucose level which was 189, IV Saline=0, SQ insulin=0 units, Glargine=0, D50=0mL and enter in the Notes section:  Glucose from previous check; Infusion paused for MRI, for example.)

Q: At 48 hours, our patient advanced to Level 3.  The patient required 18 units of SQ regular insulin in the previous 24 hours, and the glargine dose is 40% of the total insulin requirement in the previous 24 hours.  If the patient received 18 units of regular insulin, the glargine dose should be 7.2 units.  Our pharmacy says that they can’t give 7.2 units – it needs to be entered as 7 or 8 units.  How should we calculate?
A
: The glargine (Lantus) dose should be 40% of the total insulin requirement in the previous 24 hours.  This will often not be a whole number.  If >.5, round up.  If <.5, round down.  In this example, the glargine dose should be 7 units. Basal insulin should be given as close as possible to 48 hours from the time of randomization.

Q: We had a protocol deviation and erroneously dosed off of the wrong level for the SQ insulin in the control group during day 2.  The patient advanced to Level 3 at 48 hours.  How do we calculate the glargine dose?
A
: The total insulin given should be used to calculate the glargine dose rather than what would have been the correct insulin requirement.  The SQ insulin given can be summed using the SQ insulin doses for the previous 24 hours.  Once the required total units for the previous 24 hours have been summed, multiply by 0.4 to receive the glargine dose recommendation. 

Dosing errors should be reported to the local IRB per site reporting procedures.  If there is a concern about safety or urgent question about the study protocol as it relates to a dosing error, contact the SHINE study hotline. 

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Treatment Period

Q: A SHINE study patient eats all of his meals plus both of his low carb snacks between meals, and he is still hungry.  He is considering withdrawing from treatment because of the diet.  Are there any other food options that we can offer?  (NEW 1-11-15)
A
: The SHINE protocol diet includes three 60 gram carbohydrate meals daily for patients who are PO.  In addition, up to 2 low carbohydrate snacks from the protocol approved snack list may be given between each meal (up to 6 total low carbohydrate snacks daily) and unlimited protocol-approved snacks/drinks (e.g. diet sodas, sugar free Jell-O) are listed.  A list of the approved snacks is available on the study website in the Toolbox.  We would recommend working with your nutrition team in advance of enrollment to understand which diet plans are options and what snacks are available.  In addition, the diet can be modified to include more (or fewer) calories, protein and fat at each meal.

Q: Can you confirm that the 72 hours starts at randomization?  
A
: The start of protocol treatment is defined as the time of randomization, and the treatment start time is the time of randomization.  The 24 and 28 hour time-points as well as the end of the 72 hour treatment period will be based off of the randomization time.

Q: What do you do if you have an enrolled patient and have internet problems?
A
: If the local internet connection is lost and it is an intervention patient, call the SHINE Principal Investigator on call (800-915-7320 ext. 1).  The PIs have administrative rights to be able to login to each site remotely.  The site study coordinator/clinical nurse and the PI on call can work together to manage the glucose checks and insulin rate adjustments until the internet connection is again working. 

If it is a control patient, a copy of the sliding scale should be stored in hard copy or on the desktop of the study laptop.  The nurse can use the copy of the sliding scale and the study orders to manage the glucose checks and SQ insulin dosing.  A spreadsheet is posted on the study website so that the nurse/study coordinator can record the data that would normally be entered in the study laptop.  This can be entered in the control treatment screen when the internet connectivity has been restored.   The clinical or study team may also choose to contact the SHINE PI on call to help troubleshoot the laptop or internet connectivity issues.

Q: What is the definition of a protocol deviation regarding the timing of glucose checks?
A
: Glucose must be checked within 15 minutes of the scheduled time for a regular check and within 5 minutes of the scheduled time when a patient is hypoglycemic.

Q: The study protocol says that protocol-required diet is a 60 gram carbohydrate per meal diet.  Are snacks permitted?
A
: A list of the approved snacks is available on the study website in the Toolbox and the Nursing Education, Training & Tools page.  Patients who have been cleared for a PO diet may have up to 2 low carbohydrate snacks from the list between meals (up to 6 total low carbohydrate snacks daily).  Additionally, protocol-approved unlimited snacks/drinks (e.g. diet sodas, sugar free Jell-O) are listed. 

For patients in the intervention group, there is NO estimate of consumption for snacks, NO entry in GlucoStabilizer and NO insulin coverage. Snacks must be documented in the medical record. The study protocol should be followed for meal consumption estimates and meal insulin dosing for breakfast, lunch and dinner.

Q: What happens if you check a POC finger stick glucose when it is not due?  Do you enter it into the study laptop?
A
: If POC glucose is measured when not scheduled (e.g. concern for hypoglycemia, other standard care protocol or test, etc.), only enter in GlucoStabilizer/ control treatment screen if the result is <80mg/dL. 

The reason that values that are <80mg/dL should be entered is to document the POC glucose levels as they relate to the initiation of the hypoglycemia prevention and management in both treatment groups. Also, importantly, GlucoStabilizer will not know to prompt the hypoglycemia protocol for study patients in the intervention group if a level of <80mg/dL is not entered in the study laptop. 

The reason that POC glucose values should NOT be entered if >80mg/dL is that this can change the timing of next glucose check and the multiplier which is used to calculated future insulin dosing for study patients in the intervention group.  GlucoStabilizer has been programmed and validated based on entering glucose values when due per the programmed schedule for checks recommended by the decision support tool.

All POC glucose values should be documented in the clinical chart per institutional policies.

Q: What happens if there is a stroke mimic/change in the diagnosis of ischemic stroke for an enrolled study patient?
A
: In the event that at the time of enrollment, a study patient has a clinical diagnosis of ischemic stroke, but this diagnosis changes during the 72 hour treatment period, all study treatments must be stopped when the study team is made aware of the change in diagnosis.  The clinical care team will determine glucose control therapy after the SHINE treatment protocol is discontinued. 

The CRFs for the Day 1-Day 3 visits should be completed only during the period of time that the subject was receiving study treatment.  The final diagnosis and reason for premature discontinuation of the treatment protocol will be captured during the End of Treatment visit on the Study Treatment CRF. 

Even though the study treatments are stopped, the subject is still in the study should continue to be followed for the 6 week and 90 day visits.  Every effort should be made to see that these visits are completed unless the subject withdraws consent.

Q: Our hospital kitchen does not open until 6:30AM. What is the window for meals to be delivered?
A
: Per the study manual of procedures, meals are recommended to be delivered at about 06:00, 12:00 and 18:00; however, there is no window of time in which meals must be delivered, and the timing of meal delivery is not considered a protocol deviation.

Q: Our patient has had four episodes when we initiated the hypoglycemia protocol (BG<80mg/dL) in the past 24 hours.  Do we need to contact the study monitor?
A
: The MOP specifies that the study monitor must be contacted if there are 3 or more episodes of hypoglycemia (BG<70mg/dL) in a 24 hour period.  If the glucose is <80mg/dL but >70mg/dL, it is not required that you contact the safety monitor.

Q: We didn’t realize that the NIHSS needed to be assessed daily with our first enrollment.  Where do we enter it?
A
: The NIHSS much be repeated at least once daily during the treatment period, and it is strongly recommended that this be completed by a certified investigator.  The daily NIHSS should be documented in the medical record or other source documentation but is not captured in WebDCU unless there is an adverse event with neurological worsening.  The reason that the NIHSS must be assessed daily is to be able to determine whether neurological changes meet the SHINE study definition for neurological worsening.

The SHINE study definition of neurological worsening is any clinical change that is associated with a ≥4 point increase from baseline on the NIHSS score.  (Baseline is considered to be the most recent daily NIHSS or the NIHSS collected at study baseline, whichever is most recent.) Any patient with neurological worsening will be assessed for hypoglycemia and for relatedness of the hypoglycemia to neurological worsening if present.  If the patient has not returned to neurological baseline within 24 hours, a NIHSS assessment is required within 24(+/-4) hours from onset of hypoglycemic event (<70mg/dL).  If the patient has returned to neurological baseline at any point in less than 24 hours, the NIHSS is not required at 24 hours.

Per the study protocol, the full NIHSS must be assessed daily; however, in cases when this has not been captured, the documented neurological exam from that day can be converted to attain a retrospective NIHSS score.1, 2

1 Williams LS, Yilmaz EY, Lopez-Yunez AM.  Retrospective assessment of initial stroke severity with the NIH Stroke Scale. Stroke. 2000 Apr;31(4):858-62.
2 Kasner SE, Chalela JA, Luciano JM, Cucchiara BL, Raps EC, McGarvey ML, Conroy MB, Localio AR. Reliability and validity of estimating the NIH stroke scale score from medical records. Stroke. 1999 Aug;30(8):1534-7.

Q: When the blinded assessor was completing the NIHSS for the 90 day visit, a question came up about scoring.  The patient had been re-admitted and was intubated.  How do we score the NIHSS when there is an untestable item after randomization?
A
: Categories on the NIHSS may be untestable due to joint fusion or amputation at the proximal joint or due to intubation or other barriers to producing speech.  While amputation between enrollment and follow up is unlikely, it is possible that items on the NIHSS could be untestable at follow up.  In cases when this occurs, select UN for the item score.  Leave the total score blank, noting that the NIHSS cannot be summed due to untestable items when dismissing the rule violation and also in the general comments. 

Q: We are working with our dietician to make menu rotations for patients participating in SHINE.  When a nectar/honey-thickened liquid diet is ordered for the patient, the amount of carbohydrates is increased significantly.  For example, pre-thickened milk has 26 grams of carbohydrates but alone would only have 12 grams.  Is a 60 gram diet required for patients who on are a dysphagia diet?
A
: Yes, a 60 gram carbohydrate per meal diet is required for all patients who are on a PO diet.  While the amount of carbohydrates must be 60 grams/meal, the number of calories or ratios of proteins and fats are not restricted.  These components of the meal may be adjusted if there are concerns that there is not enough food due to the thickened liquids.  Sample menus from participating sites are available to share with your diet/nutrition group. 

Q: Our patient had an episode of hypoglycemia that occurred immediately after the end of the treatment period.  Is this an event that we should report?
A
: Non-serious adverse events will be reported from the time of randomization until the end of the study treatment period. The end of the study treatment period is defined as the infusion stop time, which may be prior to 72 hours from randomization. The only time that a non-serious AE is to be reported after the end of the study treatment period is a hypoglycemic event that occurs within 8 hours of stopping the study infusion and the study investigator determines to be possibly, probably or definitely related to the study treatment.  Guidelines listed in Section 8.2.2 of the study manual of procedures can be referenced to assess the relatedness of hypoglycemia (defined as glucoses <70 mg/dL) that may occur after the SHINE treatment period has ended.

Q: We have a subject enrolled in SHINE who experienced worsening of her enrolling stroke.  This has prolonged her hospitalization, so we are reporting as an SAE.  Should we use the time of her initial stroke symptom onset since this is related to that stroke?
A
: Adverse event reporting for SHINE begins at the time of randomization.  Events that occur prior to randomization are not reportable but can be included in the medical history.  In this case, the clinical event that has resulted in prolonged hospitalization should be used for the adverse event name, and the time of that event, which will be after the time of randomization, should be used as the SAE start time.  To assist study teams when drafting the event narrative, SAE templates have been drafted and are located under “SAE Templates” in the SHINE Website under Toolbox.

Q: How is diabetic ketoacidosis (DKA) being monitored in the SHINE trial?
A
: Although DKA is unlikely in the SHINE trial, it is an adverse event that we are carefully monitoring.  Most DKA occurs in patients with Type 1 diabetes, and these patients are excluded from the SHINE trial.
Things to consider in enrolled SHINE subjects include:

  1. Previous history of DKA - this increases the risk of DKA
  2. The ADA definition of DKA requires sustained very elevated glucose levels, serum bicarb < 18 mEq/L, urine ketones positive, serum ketones positive, anion gap > 10.1

In the rare event that your team makes a diagnosis of DKA for a subject enrolled in the trial, contact the study hotline to inform the PI/safety monitor on call of the event.  Management of DKA will typically require a standard care insulin drip, which will likely mean that the subject will need to be withdrawn from the treatment protocol but will continue in the SHINE study.  As always in cases where a subject is withdrawn from the treatment protocol but continues in the study, the 6 week and 3 month follow-up visits will continue per the protocol.

This is an adverse event and may meet the definition of an SAE.   If it is an SAE, specific data will be requested for the SAE narrative.  The narrative will be reviewed during the MSM review process and, if necessary, the site will be queried to provide more detailed information.

  1. If an endocrinologist’s assessment is available please provide the endocrinologist’s assessment and plan about the reported DKA event.
  2. Is there a history of a prior DKA?
  3. State if the subject has been eating & approximately how much during the SHINE protocol treatment.
  4. Provide the serum electrolytes that are available closest to the DKA diagnosis.
  5. Provide urine ketone test results that are available closest to the DKA diagnosis.
  6. Provide the blood glucose level close to the time of DKA diagnosis.
  7. If available, provide lactate levels that are available closest to the DKA diagnosis.

1Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006 Dec: 29(12):2739–48.

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Follow-up

Q: Is a hospitalization that is due to a planned or elective admission, (to treat a preexisting condition that is diagnosed before or after randomization), where there is no associated serious outcome (e.g., life-threatening; required intervention to prevent permanent impairment or damage; other serious medically important event) considered an SAE? (UPDATED 11-2-17)
A
: No, however, if any untoward medical event occurs during the hospitalization (e.g., life-threatening; required intervention to prevent permanent impairment or damage; other serious medically important event), then an SAE has occurred and should be reported within 24 hours of discovery.  Examples of planned or elective admissions, to treat preexisting conditions that are diagnosed before or after randomization may include, carotid endarterectomy to treat carotid stenosis, skin biopsy for basal cell carcinoma, colonoscopy to evaluate gastrointestinal symptoms.

Q: We just learned that our SHINE patient has been readmitted for a new stroke, and he is not yet due for his 6 week visit.  Where do we enter the SAE in WebDCU? (NEW 1-11-15)
A
: For serious adverse events (SAEs) that occur between the End of Study Treatment and the Six Week visit, complete Form 06 - Adverse Event under the last treatment day visit in WebDCU. If the study team learns of an SAE that occurred between the Six Week and 90 Day visit, the AE form that posts under the 6 week visit in WebDCU can be used to document the event.  As a reminder, SAEs must be reported and submitted within 24 hours of the time that the study team receives knowledge of the event.  Several SAE narrative templates are available in the toolbox on the SHINE study website.

Q: Can the 6 week and 90 day follow up visits be done by the same blinded individual or do they need to be completed two separate blinded investigators?
A
: These visits can be done by the same investigator, but the investigator must be blinded.

Q: The clinical care team and family have made a decision to withdraw care for a patient who has rapidly deteriorated. How do we manage for SHINE?
A
: If a decision is made to withdraw care, the study team should discuss the option for withdrawing from the study treatment with the family/LAR.  The study treatment can be stopped without a withdrawal of consent for the study.  Subjects whose treatment ends early are still in the study, and the 6 week and 90 day follow up visits must be completed unless consent is withdrawn.  The decision to stop study treatment should be documented.  Refer to Section 16 in the MOP regarding the process for discontinuation of participation and withdrawal of consent.

Q: When scheduling the 3 month follow up visit, we counted the days – starting with Day 1 during the treatment period – to see when the visit was due.  WebDCU says it is due one day later than if we count the actual days.  Which date do we use?
A
: The projected visit date that is listed in WebDCU must be used to determine the visit date and window.  The 3 month follow up visit should occur 90 days after the enrolling stroke.  Because there is a 12 hour window, the stroke and randomization can occur on different calendar days, it is defined that the outcome will be assessed 90 calendar days after randomization.  There are tools in WebDCU (Study Calendar and Subject Visit) as well as automated reminders that indicate exactly when each visit is due. 

Once a subject has been added to the study database, the study calendar will be populated with target and then actual visit dates. To view the study calendar, click on Study Calendar under ‘My Information’ on the left hand side of the main menu page.  Additionally, the visits are listed under ‘Project Management’ under ‘Subject Visit’.

The target for the 6 week follow-up visit is (+/-) 14 days.  The target for the 90-day follow-up visit is (+/-) 14 days.  Late data will be collected and analyzed for the 90 day visit with a window of (+30 days/-14 days) for the primary analysis and with a window of (+90 days/-14 days) for the secondary analyses but is a protocol deviation.

Q: We had a patient scheduled for his 90 day follow up visit that had to be rescheduled due to weather.  Because this appointment got canceled, he will be out of the target window for the visit, but he will return to clinic next week.  Are we able to do his study visit then?
A
: The target for the 90 day visit will be (+/-) 14 days. Late data will be collected and analyzed for the 90 day visit with a window of (+30 days/-14 days) for the primary outcome. In the event that the study team cannot make contact with the participant/LAR, the mRS may be assessed using information provided by caregivers or other individuals with current knowledge of the patient’s condition. Late data may be collected and analyzed for the 90 day visit with a window of (+90 days/-14 days) for secondary analyses. In the event that a subject is not lost to follow up but has missed the target for the primary analysis, it is recommended that the 90 day outcomes are captured whenever possible. SAEs will be captured from the time of randomization until the end of the study. End of study may be past 90days from randomization if the final study visit is conducted late however SAEs will not be captured past 120days from randomization or end of study, whichever occurs first.

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OmniTrace

Q: What primary function does OmniTrace provide to a clinical study?
A
: OmniTrace provides the administrative function of updating current contact information for subjects identified as LTFU or at risk of LTFU.  Our second primary area of involvement is assisting to obtain the vital status data of designated subjects. These two key functions are required to maintain study integrity by significantly reducing missing data.

Q: Does OmniTrace provide additional clinical trial support services?
AOmniTrace provides comprehensive project support including ICF language review, LTM/CRA/Site LTFU training, IRB and EC response and rebuttals, death certificate retrieval, MAE monitoring, EDC assistance, Site communication, metrics development as well as other custom services.

Q: What is OmniTrace’s experience with clinical trials?
AOmniTrace has assisted clinical trials since 2003, worked on hundreds of domestic and global studies and has successfully handled over twenty thousand requests.  OmniTrace is the premier provider of LTFU services and is the primary option when a firm has an issue with Lost to Follow-Up patients (LTFU) or is simply establishing an LTFU contingency plan.

Q: Who are OmniTrace’s typical clients?
AOmniTrace’s clients consist of Pharmaceutical Companies, CROs, AROs, Hospitals, public research institutions and government agencies such as the National Institutes of Health.

Q: Is OmniTrace licensed and insured?
AOmniTrace is licensed (A2200304) by the State of Florida as a Private Investigative Agency. OmniTrace’s current coverages include General Liability and Errors and Omissions of $2,000,000.00 per Occurrence and $2,000,000.00 Aggregate.

Q: What countries does OmniTrace provide services to?
AOmniTrace’s LTFU search capabilities are global in scope.  We also work with our clients, ethics committees and IRBs to determine if any local regulations prevent the use of our service. OmniTrace offers multiple international programs to select from or can customize a program to suit EC requirements.

Q: How long does an average search last?
AFor USA searches average turnaround time is 24 - 48 hours.  Internationally, the length of time for a search will vary by the country and program selection. Turnaround time can typically range from 3 days to 6 weeks depending on the type of search we conduct.

Q: How does OmniTrace collect information from Sites?
AOmniTrace prefers not to transmit subject data electronically as part of its standard operating procedures. Information is received and transmitted to Sites via facsimile. If faxing is not an option, we can verbally transmit information or utilize other secure means.

Q: Does OmniTrace utilize independent contractors?
AIn the USA, all searches are conducted by OmniTrace employees.  Globally, all searches are initially conducted by OmniTrace employees.  If the results of an international search are not successful, we can utilize the assistance of a local, in-country investigator but only when authorized by the client.

Q: Can OmniTrace assist us in scheduling a patient visit or collect medical data?
AOmniTrace does not get involved with patient medical issues, data collection or patient interviews. We do not access medical records as part of our search.  We only are providing the administrative function of updating contact information or providing vital status. 

Q: What information does OmniTrace need to conduct a search?
AWe typically only require the patient’s name, last known address, previous phone number and date of birth.

Q: Can you tell us about OmniTrace’s compliance?
AOmniTrace maintains strict patient privacy guidelines and data security policies. HIPAA, HITECH, GCP, EU Data Directives, Graham-Leach Bliley and other associated regulations are embedded in our processes. OmniTrace’s records and processes are open for audit and assessment.

Q: Has OmniTrace been subject to any FDA Audits?
AOmniTrace has never been subject to an FDA or regulatory audit, but our facilities and policies have been assessed and audited on multiple occasions by numerous clients.

Q: How long does OmniTrace archive subject information?
AOmniTrace only maintains hard copy records for a period of two years. No electronic records are maintained.

Q: Does OmniTrace communicate directly with IRBs and Ethics Committees?
AOmniTrace works with the Sponsor to respond to IRB/EC questions regarding our services but typically works at arm’s length versus directly.  OmniTrace will assist in answering any questions an IRB or EC may have, provide policy documents pertaining to our services, assist in preparing amendment letters and otherwise work with the sponsor, Site and EC/IRB to gain approval.

Q: Why Use OmniTrace?
A:       -Significantly reduce the number of LTFU patients

-To provide 100% vital status on all subjects

-Monitor Major Adverse Events

-Reduce FDA scrutiny

-Maximize clinical trial success 

-Eliminate missing trial data

-Allow for a faster clinical trial endpoint

-Enhance regulatory compliance and post study surveillance

-Greatly reduce clinical trial costs

Q: Can you tell us more about OmniTrace’s vital status programs?
ADomestically, OmniTrace is often requested to conduct vital status determinations on large subject populations as various endpoint and study outcome dates approach. OmniTrace provides an “alive as of date” or “date of death” along with a supporting reference. These vital status runs can be scheduled in advance or on an as needed basis.  Internationally, there is a lack of searchable death records and therefore vital status determinations are often predicated on locating the subject alive.

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Regulatory Database

Q: How can I submit regulatory documents?     
A: Follow the steps below.

  • From the main menu page, click on [Regulatory Document] and then [Site Reg Doc Status].
  • This will display a table view of the documents required at your site as well as the submission status of each document.
  • To upload a new document, click on the Add link and this will take you to [Reg Doc Submission].
  • If there are any existing documents available for selection, they will be listed.
  • If there are no existing document available, or none that you would like to select, click on the ‘upload new file’ link, browse for the document, and then click upload.
  • Enter the required information, and then click ‘Save Record.’

The document will then be in a pending status until the Trial Project Manager verifies the information and approves/accepts the document.

Q: How can I remove permissions and stop receiving regulatory document automated emails?
A: Follow the steps below.

  • Contact the coordinator in charge of adding people/submitting reg docs (usually the primary study coordinator) and request that your permissions be updated.
  • Coordinator in charge, click on [user permission request] tab.
  • Click edit record, and remove the user group [Submit Regulatory Document].

This change will be in a pending status until I approve.

Q: Where can I find the electronic Delegation of Authority (eDOA) log and how do I complete the entry? 
A:

  • Login into WebDCU-SHINE,
  • Click on the [User Management] tab
  • Click on [DOA submission]
  • Click on the blue # (number) link to the left to edit the eDOA
  • Lastly, click [Edit Record] on the top right hand corner of the page. 
  • Add the team members to the eDOA list (They need be added to the study team member request table first, see Q on “How to add NEW team member to the database?”)
  • Add responsibilities for each team member.
  • Click [Submit] for the entry to be sent to the site manager for review and approval.

Q: How do I add end date or new team member on the eDOA?
A: After CCC has approved the eDOA once, sites will then be able to edit the eDOA table again to add an end date or a new team member and resubmit updated eDOA.

  • A NEW team member needs to be added to the SHINE database first. See steps in next FAQ below.
    • Click on User management tab and then on DOA Submit table, and click on the blue # link to the left of the entry you are looking to edit
    • Click on [edit record] in the top right hand corner of the screen
    • Edit to add an end date for team member or add new team member.
    • For change in team member responsiblites, add and end date and add new tnry for same team member with udpated responsibilities

Q: How do I add a NEW team member to the database?
AAfter CCC has approved the eDOA once, sites will then be able to edit the eDOA table again to add an end date or a new team member and resubmit updated eDOA.

In order to add a team member to the SHINE database, please follow the steps below.

  • Click on [study team member request] under the user management tab
  • Click on [user permission request]. On the list record page, click on the blue # link to the left of the study team member name you are looking for
  • Once on the [user permission request] tab, click on [edit record] in the top right hand corner of the screen. Select from the drop down box in Q05 what user permissions this user should have. Click [Add new row] if an additional user group needs to be added. When done, click [save record].
  • SDMC will then review and approve the request

Q: What responsibility will need to be marked on the eDOA log for a team member to be able to randomize/complete CRFs?
AThe team member must have “CRF completion” (responsibility J) listed as one of their responsibilities in the eDOA log and the “SHINE Data Training” will be a required training.  All trainings are located on the SHINE Education and Training page. 

Q: Who is required to complete the SHINE Data training?
AStudy team members who will be performing CRF data entry MUST indicate responsibility J (CRF Completion) on the DOA log and have a SHINE Data Training Certificate uploaded.  The Abbreviated (Randomization) Training will fulfill the data training requirement for those study team members who will be doing enrollment and randomization ONLY.  All trainings are located on the SHINE Education and Training page. 

Q: How do I modify a team member’s role and/or responsibilities?
AFirst, add an end date for the team member’s whose details are being modified; then, add a new entry for the same team member with updated details for role/responsibilities and submit the eDOA for CCC review and approval.

Q: I have a new team member on my study team.  What are the steps to upload regulatory document for this new team member?
AFollow the steps below:

  • Add the new team member to the SHINE Database (See new FAQs in SHINE Website under Regulatory Database)
  • Then add the team member to the eDOA log with start date, study role, and responsibilities.
  • Submit eDOA log for CCC review and approval.
  • Upload regulatory documents for new team member, after its approved by CCC.

 Some reminders on eDOA:

  • Responsibility "G" is only to be used for pharmacists, and likewise all pharmacists must have "G" (and only G) marked in their responsibilities. They should have either PDR/SDR (primary/secondary drug recipient) marked for their respective role.   Every site needs one PDR.
  • I-SPOT responsibilities were previously noted as "Z," however, on the new electronic DOA through WebDCU, this responsibility is now "N." Please make sure that study team members involved in I-SPOT have "N" marked in the eDOA.
  • If your site is not participating in I-SPOT, please add in “notes” section of the eDOA “Site is not participating in I-SPOT.”
  • If a study team member is no longer an active AND doesn’t have an end date documented on paper DOA, they should be added to the eDOA with their start date, role, and responsibilities.  After initial acceptance of the eDOA, an end date can be added to signify they are no longer an active member.  This is to document the date of the team member’s departure for regulatory compliance purposes.

Q: How do I remove a team member's permissions from SHINE WebDCU? 
AA team member’s user account access is not updated once an end date is added to the eDOA log. Both the eDOA and user permissions have to be updated. If a team member is no longer working on SHINE, the site needs to make this member inactive by removing all of their user groups in the [user permission request] table. Please refer to the steps below.

After adding an end date on the eDOA, what are the next steps in removing a team member in SHINE?

1.      Add an end date for this user on the DOA Log under section 5: Active Team Member.

2.     Click on the [User Management] tab, and then [User Permission Request] .

3.       On the list record page, click on the blue number link to the left of the study team member name you are looking for.

3.       Click on [Edit Record] in the top right hand corner of the screen.  Remove all user group permissions in Question 5. When done, click [Save Record].

4.     SDMC Data manager will then review and approve the request.

Please feel free to contact Kavita Patel if you have any questions. 

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Other

Q: What do we do if a patient comes in and our endovascular team immediately whisks the patient away to the angio suite and subsequently intubates the patient?
A: Remember that an intubated patient cannot get a complete NIHSS score because dysarthria is unscorable.  An NIHSS score must be captured within 30 minutes of randomization.  Although the ideal situation with an endovascular patient would be to get an NIHSS score and enroll prior to intubation, potential SHINE patients who are intubated during the procedure can still be extubated and can be randomized with an NIHSS obtained within 30 minutes of randomization and if they meet all other eligibility criteria (including within 12 hours).  Please work with your clinical teams to figure out your standard of care and to ensure that all eligibility criteria are met prior to randomization. Please call the PI on call line for any and all questions.

As a reminder, patients who receive IA therapy should NOT be enrolled in ISPOT.

Q: What is an NCT number, and why would we need one for study billing?
A
: The NCT number is generated when a study is registered in the clinicaltrials.gov registry.  The NCT number is an 8 digit number always preceded by NCT.  This ClinicalTrials.gov identifier was established on June 6, 2011 for SHINE and is NCT01369069

Effective January 1, 2014, it becomes mandatory to report a “clinical trial number” on claims for items/services provided in clinical trials that are qualified for Medicare coverage.  The number that should be reported is the NCT number.  This new policy should not affect your existing billing process for SHINE.  To view the new CMS policy that goes into effect 1/1/14, please view http://www.cms.gov/Outreach-and-Education/Medicare-Learning-Network-MLN/MLNMattersArticles/Downloads/MM8401.pdf.

Q: Is there a DSMB charter for SHINE that can be provided to IRBs?
A
: There is not a DSMB charter for SHINE.  We do have NINDS Guidelines for Data and Safety Monitoring in Clinical Trials, and Section 3 of these Guidelines should satisfy IRB requirements: http://www.ninds.nih.gov/research/clinical_research/policies/data_safety_monitoring.htm#board

Q: I can’t remember if we came to resolution regarding a physician investigator being present for enrollment of subjects.  ALIAS requires a physician investigator to be physically present during enrollment, POINT requires a phone call to a physician investigator prior to randomization and ProTECT requires neither.  Where does SHINE fall in this?
A
: Enrollment will be overseen by an enrolling investigator as designated on the site Delegation of Authority Log.  Any study team member who has been delegated the responsibility to perform all of the functions required to oversee enrollment on the DOA log and is certified to do the assessments required during this visit can be an enrolling investigator.  This person does not have to be licensed.

Q: When we train on the computer using the testing area, what is the SHINE subject number?
A
: The DCU team has generated test subject IDs that can be used in the demo site and these are posted on the SHINE study website.  If a valid test ID is not entered, you will get an error message, so it is easier when training and demonstrating how to use the study laptops to make sure you have the test subject ID codes available.  Always remember to select the link for the demo site on the SHINE trial portal when using the study laptop for training so that test data are not entered into the live site.  When an actual subject is randomized in WebDCU, a four-digit SHINE subject ID will be assigned.

Q: We are curious what are you and other sites doing in view of the D50 National Shortage? Our hospital is facing a shortage which could affect the study protocol. (UPDATED 5-25-17)
A
: Due to manufacturing delays and increased demand, there is a national shortage of D50.  This shortage may or may not affect your site.  If your site is one that is affected by the shortage, we would recommend that you work with your pharmacy to consider the use of D50 bags.  If D50 bags are not available, D10 or D25 may be used (multiply IV D50 doses by 5 for equivalent IV D10 dose or multiply IV D50 doses by 2 for the equivalent IV D25 dose).  Please update your study orders and the hypoglycemia prevention and management protocol to reflect these options. For D50 shortage alternatives click here.

In the study laptop, record the equivalent dose of D50 administered.  In the intervention group, accept the D50 dose recommendation and note the volume of D10 or D25 administered in the Comments field. In the control group, enter D50 25mL in the New entry pop up and document the volume of D10 or D25 administered in the Notes field.
   

Q: The dietary team at our hospital would like to enroll our SHINE patient into a study about continuous tube feeds.  Can a SHINE patient be enrolled in another study?
A
: Patients who are enrolled in SHINE must not be enrolled in another experimental trial during the entire period of enrollment (Baseline to End of Study).  If the other study has an intervention/treatment arm and a control arm, even if the patient would be in the control arm, enrollment during the time that the patient is in SHINE is not permitted.  Participation in an observational study would require approval prior to enrollment both by the overall SHINE leadership team and the PI of the other trial.

Q: Do you have any information about how to fill out the Antithrombotic medications form?
A
: While protocols vary by site, the information below briefly describes unfractionated and low molecular weight heparin and provides common dosing regimens for reference.
#12: Unfractionated heparin: full dose anticoagulation – Heparin continuous infusion with dose adjusted to therapeutic PTT
#13: Unfractionated heparin: DVT prophylaxis – Fixed dose (usually 5,000 units) given subcutaneously twice or three times daily.
#16: LMWH: full dose anticoagulation -weight based dosing of LMWH (ex. Enoxaparin 1mg/kg sq BID).
#17: LMWH: DVT prophylaxis –fixed low dose of LMWH (ex. Enoxaparin 40mg daily or 30mg sq BID).

Common dosing regimens for LMWH and Factor Xa Inhibitor

 

DVT prophylaxis

Full dose anticoagulation (systemic)

Enoxaparin (Lovenox®)

40mg SQ daily or 30mg SQ q12

1mg/kg SQ q12 or 1.5mg/kg SQ daily

Dalteparin (Fragmin®)

2,500 or 5,000 units SQ daily

150-200 units/kg SQ daily (max 18,000 units)

Fondaparinux (Arixtra®)

2.5mg SQ daily

5-10mg SQ daily

 

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