emergency randomization proceduresshine manual of procedures 17 version 3 – january 28, 2013 the...

SHINE Manual of Procedures 16 Version 3 – January 28, 2013

4.3.2 Emergency Randomization Procedures In the event that WebDCU™ cannot be accessed (either by direct computer access, or if during normal business hours, by contacting DCU personnel), emergency randomization may occur.

Should a site have randomization questions during business hours, please contact Karen Briggs at [email protected] (843-792-3980) or Catherine Dillon at [email protected] (843-876-1942) to request a treatment assignment and subject ID. If these parties are unavailable, please call DCU’s emergency randomization hotline: 866-450-2016.

If a site has emergency randomization questions after hours or is unable to reach the DCU, the site should call the emergency randomization hotline (866-450-2016) to request the treatment assignment and subject ID.

4.4 Successful Enrollment All NETT hubs and affiliate hubs (independent sites) were surveyed using a formal data-driven instrument to establish their individual annual recruitment targets. In the case of NETT Hubs, this estimate represents the composite of the Hub together with its affiliated spokes. Based on these established individualized recruitment estimates, site performance will be formally reviewed quarterly using the “green, yellow, red” method of monitoring recruitment. Green reflects 75-100% expected enrollment, yellow 25-75% enrollment and red <25% enrollment. Sites enrolling at less than 50% of established estimates will participate in a collaborative process of developing a new strategy for recruitment in a close working partnership with Dr. Hall and the recruitment specialist. Appendix 10 includes details of the Site Recruitment Performance and Milestone Plan and Recruitment Milestones.

5. Study Treatment Procedures 5.1 Treatment Procedures The study treatment time begins at the time of randomization. Treatment should be initiated as quickly as possible following randomization.

5.1.1 Intervention and control group protocols

Intervention Group Study treatment: continuous IV insulin + subcutaneous meal insulin or

saline injections Target blood glucose: 80-130 mg/dL

Control Group Study treatment: IV saline + subcutaneous sliding scale insulin injections

Target blood glucose: <180mg/dL


The SHINE trial is a single-blinded study. Study patients will not know whether they are in the intervention or control group but will know that they will get both an IV solution and subcutaneous shots to manage high blood sugar. Both the treating and study teams will know the randomization. Care should be taken to maintain the blind. The study team is available to answer questions that study patients and their families or the treating team have about the randomization and blinding.

5.1.2 Intervention Group Study treatment: IV insulin + subcutaneous meal insulin (or saline injections for patients who are not eating) Target blood glucose: 80-130 mg/dL Once randomized to the intervention group (IV insulin + subcutaneous meal insulin or saline injections with a target blood glucose of 80-130mg/dL), the GlucoStabilizer® (decision support tool) program will be activated on the study laptop. The determination of IV and subcutaneous meal insulin dosing and instructions will be indicated by the decision support tool. The required timing of blood glucose checks will be displayed by the decision support tool. Patients will continue on study treatment for 72 hours. Discontinuation prior to 72 hour is allowed when discharge is clinically indicated and requires that all study protocol treatment must be stopped at least 6 hours in advance of scheduled discharge.

(1) IV insulin preparation (a) Drug preparation

(i) Upon randomization, the SHINE site study team will contact the pharmacy to communicate the randomization allocation. Study treatment must begin as soon as possible following randomization.

(ii) Orders for study intervention group protocol should be entered by study investigator per site procedures.

(iii) The pharmacy will provide the study IV insulin per site procedures. (iv) The concentration of the IV insulin infusion will be 1:1 (e.g. 100Units of

human regular insulin in 100 ml of normal saline (0.9% NaCl)). See Section 12-Pharmacy Manual.

(b) Study patient preparation

(i) The study team/clinical nurse will gather supplies for the IV insulin infusion protocol (IV catheter, IV tubing, infusion pump, syringes, etc.).

(ii) The SHINE study will encourage that 1 vial of Dextrose 50% in Water (D50) be stored to allow immediate availability at the bedside. If hypoglycemia occurs, patients in the intervention group will receive an individualized dose of D50 as indicated by the GlucoStabilizer® tool. For this reason, syringes with graduated marks for volume (mL) must be used.

(iii) An IV for study medication only will placed. All other IV medications should be administered separately from the IV for study insulin infusion.

(iv) Upon receipt of the IV insulin bag from the pharmacy, the study team/clinical nurse will hang it with an infusion pump. The IV infusion pump should be programmed to maintain the blind (i.e., the display on the infusion pump should read SHINE Study Drug rather than insulin).

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(6) Additional steps for blood glucose <70mg/dL If the blood glucose drops <70 mg/dL, the following additional actions are required:

(i) Continue to use the hypoglycemia protocol above (e.g. hold insulin, give D50, repeat glucose checks every 15 minutes).

(ii) Draw a STAT laboratory serum glucose measurement but do not delay treatment with D50 by waiting for this blood draw result. Only the results from POC glucose checks should be used for study treatment dosing. The study coordinator will document the result of the serum glucose measurement.

(iii) Screen the patient for hypoglycemia symptoms using Hypoglycemia Symptomatic Questionnaire. 1. The worksheet and instructions will be available on paper and on the

desktop of the laptops. 2. The Hypoglycemia Symptomatic Questionnaire must be repeated

every 15 minutes when glucose is <70mg/dL. 3. Once the glucose is ≥ 70mg/dL or the symptoms have resolved,

whichever comes first, one final assessment with the Hypoglycemia Symptomatic Questionnaire is required

4. Once the glucose is ≥80 mg/dL, the timing of glucose checks and insulin infusion rate will again be determined by the GlucoStabilizer®.

(iv) Screen the patient for neurological worsening.

1. An assessment of neurological change is required per site standard care (“neuro check”) every 15 minutes when glucose is <70mg/dL even if there are no new neurological findings

2. The SHINE study definition of neurological worsening will be considered 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.)

3. Any patient with neurological worsening will be assessed for hypoglycemia and for relatedness of the hypoglycemia to neurological worsening if present.

4. 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.

5. If neurological worsening (persists for greater than or equal to 24 hours) is associated with a glucose concentration <55mg/dL, an SAE form is required.

(v) If the glucose falls below 40mg/dL at any time, an SAE form is required.

(7) Meal insulin for the intervention group

(a) General concepts-SHINE protocol-recommended diet 1. 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. Meals will be encouraged, but not required, to be delivered at approximately 06:00, 12:00 and 18:00.


2. Patients receiving tube feeds may receive bolus or continuous tube feeds per standard care. Bolus tube feeds will also be encouraged to be given at around 06:00, 12:00 and 18:00.

3. Dietary teams should be involved in assuring that the 60 grams/meal carbohydrate diets are maintained throughout the study protocol.

4. About twenty minutes after the initiation of a meal assess meal consumption. If the patient is not finished eating, an assessment of the likely total consumption is required.

5. 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.

i. Full or near full consumption 60 grams carbohydrates ii. No or nearly no consumption 0 grams carbohydrates iii. Partial consumption 30 grams carbohydrates

6. Note that only 30 grams or 60 grams can be entered into GlucoStabilizer®. No other values should be entered or GlucoStabilizer® will recommend an incorrect meal insulin dose.

7. 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. No injection is given.

8. Patients should not consume additional food not included on the meal tray from the hospital kitchen aside from protocol-approved snacks.

9. Family, friends and visitors should be instructed not to consume food from the patient’s trays unless approved by the nurses, after patients finish eating.

(b) Protocol-approved snacks SHINE patients may also consume up to 2 low carbohydrate snacks (<5 grams carbohydrates per serving) from the list below between meals (up to 6 low carbohydrate snacks daily). The study protocol diet does not limit the consumption of sugar free foods and drinks listed in the unlimited category below. Patients should only consume food included on the meal tray from the hospital kitchen or the protocol approved snacks during the 72 hour treatment period. 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. Low carbohydrate snack options (up to 2 between meals) 5 celery sticks + Tablespoon peanut butter 5 baby carrots 5 cherry tomatoes + 1 Tablespoon ranch 1 hard-boiled egg ½ cup raw broccoli + 1 Tablespoon ranch 1 cup cucumber slices + 1 Tablespoon ranch dressing ¼ cup of fresh blueberries 1 cup of salad greens, 1/2 cup of diced cucumber, and with vinegar and oil 2 saltine crackers


1 piece of string cheese stick ½ cup of egg salad, tuna salad or chicken salad 3 oz of deli ham, chicken or turkey slices 1 serving of cubed or sliced cheese (1 oz) ½ cup cottage cheese ½ cup tofu 1 slice deli ham, chicken or turkey + 1 slice cheese Unlimited Bouillon and broth Club soda, unsweetened Diet soft drinks Flavoring extracts Horseradish Mineral water Mustard Pickles Soy sauce Spices Sugar-free drink mixes Sugar-free gum Sugar-free Jell-O Tabasco or hot sauce Unsweetened lemon or lime juice Unsweetened tea Vinegar

(c) Subcutaneous meal insulin dosing using GlucoStabilizer® 1. The GlucoStabilizer® will indicate the meal insulin dose for patients who

are eating based on the quantity of carbohydrates in a meal and the specified insulin to carbohydrate ratio (1:15). This means that one unit of insulin will cover 15 grams of carbohydrates consumed.

2. Only rapid acting analog insulin (Humalog, Novolog, and Apidra are all acceptable rapid acting analog insulins) will be used to cover meal carbohydrates. Human regular insulin (Humulin R or Novolin R) MUST NOT be used for subcutaneous injections in the intervention group. (See Section 12- Pharmacy Manual)

3. Follow study site protocol for obtaining rapid acting analog insulin and syringes for subcutaneous injections. a. Nurses will prepare and inject the rapid acting analog insulin

according to the recommendation of the GlucoStabilizer®. b. The meal insulin will be given after assessment of consumption. c. The GlucoStabilizer® will determine the meal insulin dose. If the

patient has consumed part or all of the meal, select the option to Cover Carbs on the GlucoStabilizer® main page.

SHINE MVersion 3


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3. 10-49 grams carbohydrates/bolus Enter 30 grams carbohydrates in GlucoStabilizer®

(iv) If a glucose check is due at nearly the same time as the bolus tube feed, check glucose first and adjust the infusion prior to giving the bolus.

(d) NPO or Continuous tube feeds

(i) Continuous tube feeds - For patients receiving continuous tube feeds, no meal insulin is given. Patients who are receiving continuous tube feeds will receive placebo saline subcutaneous injections TWO times per day. Continuous tube feeds should include approximately 180 grams of carbohydrates per day. Special instructions are provided on the study protocol when there are interruptions in continuous tube feeds (see Section 9 - Procedure for interruptions in continuous tube feeds below).

(ii) NPO – For patients who are NPO, no meal insulin is given. Patients who are NPO will receive placebo saline subcutaneous injections TWO times per day.

(iii) Subcutaneous saline injections (only for patients who are not eating AND in intervention group of study) Subcutaneous injections will be given at meal time up to three times a day for patients who are eating. Patients who are not eating or are receiving continuous tube feeds will receive placebo saline subcutaneous injections TWO times per day (at approximately 9:00 and 21:00 associated with the glucose check). The clinical/research nurses will prepare and inject subcutaneously 0.05 ml of sterile saline using 1cc syringes. The subcutaneous saline injections are needed to maintain the blind and simulate the 0-4 subcutaneous insulin injections in the control group. Only patients that are NPO (nothing by mouth) or on full continuous tube feeds AND in the intervention group should get the saline injections.

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(c) Patients who discontinue study treatment are required to do so 6 hours prior

to actual discharge from the hospital. (d) After the SHINE protocol ends, the clinical care team will determine inpatient

and outpatient glucose control therapy. The treatment should be based upon on ADA/AACE guidelines and individual patient needs.28

(e) The table below offers information to consider for hospitalized patients requiring glucose control. These guidelines are not part of the SHINE protocol and are not required actions.

Considerations for the transition from study treatment to standard clinical care

Option Comment

Intravenous insulin drip Consider IV insulin therapy in some critically ill patients per ADA guidelines.

SQ insulins, including regular, rapid-acting analog, and long-acting basal

Per ADA guidelines scheduled subcutaneous insulin that delivers basal, nutritional, and correction components is preferred.

An example of basal insulin is Lantus (glargine) SQ QD calculated based on previous 24 hour insulin requirements and given when the drip is being discontinued as suggested below.

An example of nutritional insulin (for patients who are eating) is rapid acting analog SQ insulin dosing based on meal carbohydrate consumption.

An example of correction insulin is regular SQ insulin dosing based on blood glucose level per sliding scale protocol.

ADA guidelines caution against hyperglycemia escape when a patient is transitioned from intravenous to subcutaneous insulin therapy. An option to consider after stopping the SHINE insulin infusion, depending on individual patient needs, may be to give basal insulin right after the IV insulin is stopped. Check blood glucose in 30-60 minutes, and give SQ insulin to correct hyperglycemia as needed. Then consider continuing with a standard SQ insulin protocol.

Oral agents and injectable noninsulin therapies

Consider that oral agents are not recommended in hospitalized patients, but may be initiated or resumed in anticipation of discharge per ADA guidelines.

Hospital discharge education and instructions

Consider individualized discharge planning per ADA guidelines.

SHINE MVersion 3


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then approximately every 3 hours for the remainder of the study treatment period. The schedule for these checks is 03:00, 06:00, 09:00, 12:00, 15:00, 18:00, 21:00 and 24:00

(d) Glucose must be checked with 15 minutes of the scheduled time for a regular check and within 5 minutes of the scheduled time when a patient is hypoglycemic.

(e) Only the results of POC glucose should be recorded in the control treatment screen of study laptop. Lab glucose levels should NOT be entered!

(f) In the control group, the timing of POC glucose monitoring is displayed on the control treatment screen of the study laptop for the duration of the study treatment period.

(g) If the blood glucose drops <80 mg/dL, the hypoglycemia prevention and management protocol will be initiated.

(3) Control treatment protocol

(a) Overview (i) SHINE study laptops will be supplied to all participating sites and must be

used to access the control treatment screen. The icon for the SHINE portal will be located on the desktop of the laptop. Study laptops are to remain powered on and open throughout the treatment period. The screens for the control group will allow the clinical nurses to see the sliding scale table and timing for glucose checks. The glucose levels, subcutaneous insulin administered and saline infusion rates will be entered in the control treatment screen. The sliding scale table will have three levels of dosing (Level 1, Level 2 and Level 3). Changes in the level of dosing will occur only if indicated and only at 24 and 48 hours after the initiation of study treatment (time of randomization).

(ii) Administrative set up instructions 1. Retrieve the study laptop and ensure internet connectivity per site

procedures. 2. The initial setup for each subject will be done by the site study team. 3. The login for the computer is the SHINE user profile, and the

password is shine. 4. The GlucoStabilizer® login will be User ID: shine, Password: shine

for all personnel and all sites. Contact the study team with questions about the login.

5. The SHINE subject ID is unique identification number for each randomized patient. This will be provided by the study team after the patient has been randomized in WebDCUTM.

(iii) Initiating IV saline/subcutaneous insulin

1. Select the icon for the SHINE Trial Portal on the desktop.

SHINE MVersion 3


ocedures 28, 2013

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c. Follow instructions above for glucose checks, saline infusion and subcutaneous insulin injections.

(iii) If a patient proceeds to Level 3:

1. Give a one-time subcutaneous basal insulin injection {Glargine (Lantus)} at a dose of 40% of previous 24 hours entire insulin requirement.

2. Calculate the dose of basal insulin. a. Sum the total insulin requirement from all 4 previous dosing times

in calculation of 24 hour insulin requirement. b. Round down if <.4 and round up if >.5

3. Basal insulin (Glargine) will be requested from pharmacy per site procedures.

4. This dose of basal insulin should be given approximately at the 48 hour point regardless of time of day.

5. Record the dose of basal insulin by entering New Event. The pop up will display. a. If not a dosing time, enter the following values.

i. Time: actual time given (do not change unless incorrect) ii. Glucose: enter the previous glucose value (because this

cannot be blank or 0) and note that this is the value is from the last scheduled check.

iii. SQ insulin: If it is not a SQ dosing time, enter 0 as no SQ insulin dose should be administered

iv. D50: Enter 0 as no D50 should be administered v. Basal: Enter the dose given vi. Note: Since not a scheduled glucose check time, type

‘previous value entered because not a scheduled check time’ vii. Select next and re-enter values and select OK.

b. If it is a dosing time, enter the following values: i. If the 48 hour point is within 15 minutes of a glucose check,

check POC, give SQ insulin per protocol. ii. Time: actual time given (do not change unless incorrect) iii. Glucose: enter the POC glucose value iv. SQ insulin: enter the SQ regular insulin dose based on sliding

scale if one of the scheduled dosing times (06:00, 12:00, 18:00 or 21:00).

v. D50: Enter 0 as no D50 should be administered vi. Basal: Enter the dose given vii. Note: Note that this was a scheduled glucose check time as

well as the time of the 48 hour/glargine (Lantus) dose time viii. Select next and re-enter values and select OK.

6. Continue Level 3 of the sliding scale insulin dose. 7. Follow instructions above for glucose checks, saline infusion and

subcutaneous insulin injections.

(iv) After 72 hours on study protocol, study treatment should be discontinued.

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d. Once the glucose is ≥80 mg/dL, the timing of glucose checks and insulin infusion rate will again be determined by the control treatment screen.

4. Screen the patient for neurological worsening. a. An assessment of neurological change is required per site

standard care (“neuro check”) every 15 minutes when glucose is <70mg/dL even if there are no new neurological findings.

b. The SHINE study definition of neurological worsening will be considered 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.)

c. Any patient with neurological worsening will be assessed for hypoglycemia and for relatedness of the hypoglycemia to neurological worsening if present.

d. 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.

e. If neurological worsening persists for greater than or equal to 24 hours and is associated with a glucose concentration of <55mg/dL, an SAE form is required. If the glucose falls below 40mg/dL at any time, an SAE form is required.

5. For any study patient in the control group who experiences 3 or more episodes of hypoglycemia (glucose concentration of <70mg/dL in a 24 hour period), contact the Independent Safety Monitor (800-915-7320 ext 2). At the 24 and 48 hour intervals, regardless of the previous two glucose measurements, do NOT advance to a higher level on the subcutaneous sliding scale.

(5) Meals

(a) Patients who are PO (i) SHINE protocol-recommended diet for the control group

All patients in the control group who pass a swallow test and are cleared to eat will have a 60 gram carbohydrate diet. The 60 gram carbohydrate diet should be ordered for breakfast, lunch and dinner as a part of standard care. Meals should be delivered at about 06:00, 12:00 and 18:00. Meals will be withheld until subcutaneous insulin is given per the study schedule for glucose checks and sliding scale for insulin dosing occurring at meal time. Meal insulin will not be given in this group.

(ii) Protocol-approved snacks

SHINE patients may also consume up to 2 low carbohydrate snacks (<5 grams carbohydrates per serving) from the list below between meals (up to 6 low carbohydrate snacks daily). The study protocol diet does not limit the consumption of sugar free foods and drinks listed in the unlimited category below. Patients should only consume food included on the meal tray from the hospital kitchen or the protocol approved snacks during the 72 hour treatment period.


Low carbohydrate snack options (up to 2 between meals) 5 celery sticks + Tablespoon peanut butter 5 baby carrots 5 cherry tomatoes + 1 Tablespoon ranch 1 hard-boiled egg ½ cup raw broccoli + 1 Tablespoon ranch 1 cup cucumber slices + 1 Tablespoon ranch dressing ¼ cup of fresh blueberries 1 cup of salad greens, 1/2 cup of diced cucumber, and with vinegar and oil 2 saltine crackers 1 piece of string cheese stick ½ cup of egg salad, tuna salad or chicken salad 3 oz of deli ham, chicken or turkey slices 1 serving of cubed or sliced cheese (1 oz) ½ cup cottage cheese ½ cup tofu 1 slice deli ham, chicken or turkey + 1 slice cheese Unlimited Bouillon and broth Club soda, unsweetened Diet soft drinks Flavoring extracts Horseradish Mineral water Mustard Pickles Soy sauce Spices Sugar-free drink mixes Sugar-free gum Sugar-free Jell-O Tabasco or hot sauce Unsweetened lemon or lime juice Unsweetened tea Vinegar

(iii) Patients receiving tube feedings may receive either bolus or continuous tube feedings per standard care. Bolus tube feedings will be encouraged to be given at around 06:00, 12:00 and 18:00 and will also be 60 gram carbohydrate per feed.

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(8) Stopping study treatment when there is a change in diagnosis of ischemic stroke/stroke mimic (a) In the event that there is a change in the diagnosis of ischemic stroke during

the 72 hour treatment period, all study treatments should be stopped at the time that the study team receives knowledge of the new diagnosis.

(b) The clinical care team will determine glucose control therapy after the SHINE treatment protocol is discontinued.

(c) Instructions for completing CRFs when the study treatment is stopped due to a change in diagnosis of ischemic stroke (i) The Day 1-Day 3 visits should be completed only during the period of

time that the patient was receiving study treatment. (ii) The final diagnosis will be captured on the Study Treatment CRF (Form

15) as: Migraine, Seizure, Brain tumor/mass, Psychogenic, Anamnestic syndrome, CNS Infection (abscess, meningitis, encephalitis), Toxic/metabolic (encephalopathy) and Other: specify).

(iii) A brief narrative explaining the change in diagnosis is required. This narrative should include sufficient information to demonstrate that the new diagnosis is most likely including appropriate imaging and laboratory data.

(iv) On the Study Treatment CRF (Form 15), the study treatment status should be captured as: Started but discontinued prior to 72 hours of study treatment

(d) The End of Study Visit must be completed. Unless consent is withdrawn, patients whose treatment ends early are still in the study and the 6 week and 90 day follow up visits must be completed in addition to the End of Study Visit.

(9) Transition from study treatment (a) The start time for the study treatment period is the time of randomization.

The treatment period will be 72 hours or until the time of discharge from the hospital, whichever comes first.

(b) Patients who discontinue study treatment are required to do so 6 hours prior to actual discharge from the hospital.

(c) After the SHINE protocol ends, the clinical care team will determine inpatient and outpatient glucose control therapy. The treatment should be based upon on ADA/AACE guidelines and individual patient needs. 28

(d) The table below offers information to consider for hospitalized patients requiring glucose control. These guidelines are not part of the SHINE protocol and are not required actions.

Considerations for the transition from study treatment to standard clinical care

Option Comment

Intravenous insulin drip Consider IV insulin therapy in some critically ill patients per ADA guidelines.

SQ insulins, including regular, rapid-acting analog, and long-acting

Per ADA guidelines scheduled subcutaneous insulin that delivers basal, nutritional, and correction components is preferred.

An example of basal insulin is Lantus (glargine) SQ QD


basal calculated based on previous 24 hour insulin requirements and given when the drip is being discontinued as suggested below.

An example of nutritional insulin (for patients who are eating) is rapid acting analog SQ insulin dosing based on meal carbohydrate consumption.

An example of correction insulin is regular SQ insulin dosing based on blood glucose level per sliding scale protocol.

ADA guidelines caution against hyperglycemia escape when a patient is transitioned from intravenous to subcutaneous insulin therapy. An option to consider after stopping the SHINE insulin infusion, depending on individual patient needs, may be to give basal insulin right after the IV insulin is stopped. Check blood glucose in 30-60 minutes, and give SQ insulin to correct hyperglycemia as needed. Then consider continuing with a standard SQ insulin protocol.

Oral agents and injectable noninsulin therapies

Consider that oral agents are not recommended in hospitalized patients, but may be initiated or resumed in anticipation of discharge per ADA guidelines.

Hospital discharge education and instructions

Consider individualized discharge planning per ADA guidelines.

5.1.4 Considerations for Study Coordinators during the Treatment Period

Study team should: 1. Shift change, meals, end of each 24 hour period during the treatment period 2. Establish site procedures to ensure that study coordinator is notified if

hypoglycemia, severe hyperglycemia or neurologic changes occur. 3. When a study patient experiences study defined neurological worsening,

capture the NIHSS score 24 hours (+/-4 hours) after the start of the hypoglycemic event (blood glucose < 70mg/dL).

4. Be notified if patient planned for discharge. This is particularly important if the patient will be discharged before 72 hours as the study treatment must be discontinued at least 6 hours prior to discharge.

5. Confirm that the NIHSS score is captured each day. 6. Review the Daily Care Log and ensure that data is being captured accurately

and that meals are being ordered and recorded per protocol. 7. Control group – hourly checks to q3 hour scheduled check times and 8. Assist in planning the transition to standard care.

The study team will receive automated daily email notifications at 24, 48 and 72 hours based on the time of randomization. The purpose of this daily email is to remind the study team of the time in treatment to consider discharge and remind of the 24, 48 and 72 hours and level changes in the control sliding scale.


5.1.5 Concomitant or Ancillary Therapy Throughout the study period, all AHA guidelines for acute stroke care will be followed. This includes standard care for acute ischemic stroke patients such as swallowing evaluation prior to initiation of PO intake, DVT prophylaxis and secondary stroke prevention therapies. Blood pressure and temperature recommendations also will be followed. Rehabilitation evaluation should be considered for every study patient.

6. Event Visits 6.1 Study Visit Schedule

Abbreviated schedule of events in SHINE trial

Event

Screen* Baseline*

Up to 3 days of Rx

Complete Rx/ D/C**

6 wks

90 days

Informed Consent x Eligibility Assessment x Randomization x Study drug given x --- ------► POC glucose check x x --- ------►

mRS x x BI x NIHSS x x (daily) x x SSQOL x SAE/AEs* x --- ------► -------► -----► x Protocol Deviations x --- ------► ------► ------► x Neuro worsening x --- ------► -------► Lacunar subtype x *Screening is during eligibility assessment; baseline is at time of randomization. AEs will be followed through the treatment period only. SAEs will be reported throughout the study. **Completion of 72 hr treatment period unless discharged prior to 72 hrs

6.2 Assessments

6.2.1 Blinding of follow up visits The 6 week and 3 month follow up assessments should be completed by a blinded study team member. SAEs can be assessed by a study team member who is unblinded to study treatment assignment.

6.2.2 mRS29-31 The modified Rankin Scale (mRS) is a stroke scale used to assess the severity of functional impairment after stroke. It consists of six levels (0-5) not including death. Zero indicates no symptoms at all and 5 indicates severe disability.

The mRS will be scored at all time-points by a certified investigator. The person collecting the mRS score at 6 weeks should be blinded to the subject’s initial treatment. It is mandatory that the 90-day mRS be scored by a study team member who is blinded to the subject’s treatment group.

The mRS is always assessed using the level of disability at the current time and should never be retrospective.

emergency randomization proceduresshine manual of procedures 17 version 3 – january 28, 2013 the...

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