Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial

Phase 3

Completed

Conditions: Acute Ischemic Stroke
Diabetes
Hyperglycemia

Interventions: 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

Registration Number: NCT01369069

Lead Sponsor: University of Virginia

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1151

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IV insulin drip with target glucose 80 mg/dL - 130 mg/dL	IV insulin to maintain target glucose concentration of 80-130 mg/dL	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.
Sub Q insulin to keep glucose less than 180 mg/dL	Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL	This standard care arm will get sub q insulin sliding scale to keep glucose concentration less than 180 mg/dL

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Favorable Modified Rankin Scale (Yes/No)	90 days (-14/+30 days)	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.
Number of Participants With Severe Hypoglycemia (Blood Glucose < 40mg/dL)	72 hours	Severe hypoglycemia (blood glucose \< 40mg/dL) is the primary safety outcome and will be measured during the 72 hour treatment period.

Secondary Outcome Measures

Name	Time	Method
Stroke Specific Quality of Life (SSQOL)	Follow up (Max 164 days)	Stroke Specific Quality of Life. Scores range from 1-5 with higher scores indicating better quality of life
Number of Participants With a Favorable NIHSS	Follow up (Max 164 days)	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.
Number of Participants With a Favorable Barthel Index	Follow up (Max 164 days)	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.

Trial Locations

Locations (70): Northwestern Memorial Hospital
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Chicago, Illinois, United States
Ronald Regan Medical Center
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Los Angeles, California, United States
UT Southwestern-Parkland Memorial Hospital
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Dallas, Texas, United States
UT Southwestern-Zale Lipshy University Hospital
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Dallas, Texas, United States
Tufts Medical Center
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Boston, Massachusetts, United States
Harborview Medical Center
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Seattle, Washington, United States
Hennepin County Medical Center
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Minneapolis, Minnesota, United States
University of Arizona Medical Center - South Campus
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Tucson, Arizona, United States
Long Beach Memorial Medical Center
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Long Beach, California, United States
Stanford University Medical Center
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Stanford, California, United States
Mayo Clinic Jacksonville
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Jacksonville, Florida, United States
Jackson Memorial Hospital
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Miami, Florida, United States
Emory University Hospital - Midtown
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Atlanta, Georgia, United States
Emory University Hospital
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Atlanta, Georgia, United States
Grady Memorial Hospital
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Atlanta, Georgia, United States
Augusta University Medical Center
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Augusta, Georgia, United States
OSF Saint Francis Medical Center
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Peoria, Illinois, United States
University of Iowa Hospitals & Clinics
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Iowa City, Iowa, United States
University of Kentucky
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Lexington, Kentucky, United States
University of Maryland Medical Center
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Baltimore, Maryland, United States
Massachusetts General Hospital
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Boston, Massachusetts, United States
William Beaumont Hospital-Troy
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Troy, Michigan, United States
William Beaumont Hospital-Royal Oak
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Royal Oak, Michigan, United States
University of Minnesota Medical Center, Fairview
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Minneapolis, Minnesota, United States
JFK Medical Center
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Edison, New Jersey, United States
Lincoln Medical and Mental Health Center
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Bronx, New York, United States
Kings County Hospital
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Brooklyn, New York, United States
Buffalo General Medical Center
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Buffalo, New York, United States
SUNY Downstate University Hospital of Brooklyn
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Brooklyn, New York, United States
The Mount Sinai Medical Center
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New York, New York, United States
Columbia University Medical Center
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New York, New York, United States
Summa Akron City Hospital
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Akron, Ohio, United States
Wexner Medical Center
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Columbus, Ohio, United States
Miami Valley Hospital
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Dayton, Ohio, United States
Penn State Hershey Medical Center
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Hershey, Pennsylvania, United States
Thomas Jefferson University Hospital
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Philadelphia, Pennsylvania, United States
Hospital of the University of Pennsylvania
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Philadelphia, Pennsylvania, United States
Temple University Hospital
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Philadelphia, Pennsylvania, United States
UPMC Presbyterian
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Pittsburgh, Pennsylvania, United States
Allegheny General Hospital
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Pittsburgh, Pennsylvania, United States
UPMC - Mercy
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Pittsburgh, Pennsylvania, United States
WellSpan York Hospital
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York, Pennsylvania, United States
Valley Baptist Medical Center
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Harlingen, Texas, United States
Baylor College of Medicine
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Houston, Texas, United States
Memorial Herman Hospital
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Houston, Texas, United States
University of Arizona
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Tucson, Arizona, United States
MedStar Washington Hospital Center
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Washington, District of Columbia, United States
West Virginia University
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Morgantown, West Virginia, United States
Abington Memorial Hospital
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Abington, Pennsylvania, United States
University of Cincinnati
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Cincinnati, Ohio, United States
University of Virginia
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Charlottesville, Virginia, United States
Maimonides Medical Center
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New York, New York, United States
Hackensack University Medical Center
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Hackensack, New Jersey, United States
Weill Cornell Medical Center
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New York, New York, United States
San Francisco General Hospital
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San Francisco, California, United States
California Pacific Medical Center - Davies Campus
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San Francisco, California, United States
UCSF Medical Center
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San Francisco, California, United States
California Pacific Medical Center-Pacific Campus
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San Francisco, California, United States
University of Michigan
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Ann Arbor, Michigan, United States
Detroit Receiving Hospital
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Detroit, Michigan, United States
Henry Ford Health System
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Detroit, Michigan, United States
Sinai-Grace Hospital
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Detroit, Michigan, United States
St. Thomas Neuroscience Research Institute
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Nashville, Tennessee, United States
Vanderbilt University Medical Center
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Nashville, Tennessee, United States
University of Utah
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Salt Lake City, Utah, United States
Froedtert Memorial Hospital
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Milwaukee, Wisconsin, United States
Dell Seton Medical Center at UT
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Austin, Texas, United States
Seton Medical Center
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Austin, Texas, United States
Virginia Commonwealth University
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Richmond, Virginia, United States
University of Kansas Medical Center
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Kansas City, Kansas, United States