Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial

Study Overview
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Brief Summary
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The Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial is a multicenter, randomized, controlled clinical trial of 1400 patients that will include approximately 60 enrolling sites. The study hypotheses are that treatment of hyperglycemic acute ischemic stroke patients with targeted glucose concentration (80mg/dL - 130 mg/dL) will be safe and result in improved 3 month outcome after stroke.

Detailed Description
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Eligible subjects must be randomized within 12 hours of stroke symptom onset and either have type 2 diabetes and glucose concentrations of over 110 mg/dL or no history of diabetes and glucose concentrations of 150 mg/dL or higher on initial evaluation. The enrolling sites include the Neurological Emergencies Treatment Trials (NETT) sites as well as non NETT sites from all over the United States. The study evaluates the safety and efficacy of targeted glucose control (treatment group - IV insulin with target 80-130 mg/dl) verses control therapy of sub q insulin plus basal insulin with target glucose less than 180 mg/ dL.

Official Title
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Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial

Conditions
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Diabetes, Acute Ischemic Stroke, Hyperglycemia

Intervention / Treatment
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* Drug: IV insulin to maintain target glucose concentration of 80-130 mg/dL
* Drug: Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Clinical diagnosis of ischemic stroke defined as acute neurological deficit occurring in one or more cerebral vascular territories. Neuroimaging must be done to exclude intracranial hemorrhage (ICH). Randomization must be within 12 hours after stroke symptom onset and treatment is recommended, but not required, to begin within 3 hours after hospital arrival. If time of symptom onset is unclear or patient is awakening with stroke symptoms, the time of onset will be the time the patient was last known to be normal. Known history of type 2 diabetes mellitus and glucose >110 mg/dL OR admission blood glucose ≥150 mg/dL in those w/o known diabetes mellitus Baseline NIHSS score of 3-22 Pre-stroke modified Rankin Scale score = 0 for patients with an NIHSS score of 3-7. Pre-stroke modified Rankin Scale score = 0 or 1 for patients with an NIHSS score of 8-22. Able to provide a valid informed consent to be in the study (self or their authorized legally accepted representative). The approved consent form must be signed and dated in accordance with federal and institutional guidelines. Exclusion Criteria: Known history of type 1 diabetes mellitus Substantial pre-existing neurological or psychiatric illness that would confound the neurological assessment or other outcome assessment Having received experimental therapy for the enrollment stroke. IV tPA (up to 4.5 hrs) or IA tPA are allowed as are IA therapies including use of FDA cleared devices. Non FDA cleared devices are considered experimental and are excluded. Pregnant or breast-feeding at the time of study entry Other serious conditions that make the patient unlikely to survive 90 days Inability to follow the protocol or return for the 90 day follow up Renal dialysis (including hemo or peritoneal dialysis)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV insulin drip with target glucose 80 mg/dL - 130 mg/dL<br>The intervention arm will have a targeted glucose concentration of 80-130 mg/dL. IV insulin drip will be titrated to keep glucose concentration in this range. | Drug: IV insulin to maintain target glucose concentration of 80-130 mg/dL<br>* Intervention is to keep glucose concentration 80-130 mg/dL for up to 72 hours after randomization. IV insulin drip will be used to maintain glucose target.<br>* Other names: Continuous intravenous insulin;|
| Active Comparator: Sub Q insulin to keep glucose less than 180 mg/dL<br>This standard care arm will get sub q insulin sliding scale to keep glucose concentration less than 180 mg/dL | Drug: Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL<br>* Sliding scale sub q insulin given will be given up to 4 times per day based on glucose concentration. It will be given only if glucose concentration greater than or equal to 180 mg/dL.<br>* Other names: Sliding scale insulin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Favorable Modified Rankin Scale (Yes/No) | Favorable for the primary efficacy outcome is defined as modified Rankin Scale (mRS) score of 0 in patients with mild stroke (baseline NIHSS 3-7), mRS 0 or 1 in patients with moderate stroke (baseline NIHSS 8-14), and mRS 0, 1 or 2 in patients with severe stroke (baseline NIHSS 15-22) at 90 days with a pre-specified range of acceptable days of 76 -120 days. The mRS is a stroke outcome scale used to assess functional status after stroke. It consists of seven levels (0-6) where 0 indicates no residual symptoms at all, 5 indicates severe disability and 6 indicates death. The person collecting the mRS score was to be blinded to the participant's treatment group assignment. | 90 days (-14/+30 days) | 
| Number of Participants With Severe Hypoglycemia (Blood Glucose < 40mg/dL) | Severe hypoglycemia (blood glucose < 40mg/dL) is the primary safety outcome and will be measured during the 72 hour treatment period. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Favorable NIHSS | The NIHSS (National Institutes of Health Stroke Scale) score ranges from 0 to 42, with higher scores indicating greater neurological deficits. A favorable NIHSS was defined as a score of 0 or 1 on the NIHSS at 90 days post randomization. | Follow up (Max 164 days) | 
| Number of Participants With a Favorable Barthel Index | Favorable outcomes for the Barthel Index was defined as a score of 95-100 on the BI at 90 days post randomization. Barthel - Barthel Index for Activities of Daily Living (ADL) assesses functional independence, generally in stroke patients. Scores range from 0-100 with higher scores indicating greater ability to perform activities of daily living. | Follow up (Max 164 days) | 
| Stroke Specific Quality of Life (SSQOL) | Stroke Specific Quality of Life. Scores range from 1-5 with higher scores indicating better quality of life | Follow up (Max 164 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, hyperglycemia, stroke