Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial

NCT ID: NCT01369069

Last Updated: 2019-12-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1151 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-04-30

Study Completion Date

2018-11-19

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.

Conditions

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Acute Ischemic Stroke Diabetes Hyperglycemia

Keywords

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stroke diabetes hyperglycemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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IV insulin drip with target glucose 80 mg/dL - 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.

Group Type EXPERIMENTAL

IV insulin to maintain target glucose concentration of 80-130 mg/dL

Intervention Type DRUG

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.

Sub Q 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

Group Type ACTIVE_COMPARATOR

Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL

Intervention Type DRUG

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.

Interventions

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IV insulin to maintain target glucose concentration of 80-130 mg/dL

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.

Intervention Type DRUG

Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL

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.

Intervention Type DRUG

Other Intervention Names

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Continuous intravenous insulin Sliding scale insulin

Eligibility Criteria

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Inclusion Criteria

1. Age 18 years or older
2. 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).
3. 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.
4. 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
5. Baseline NIHSS score of 3-22
6. 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.
7. 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

1. Known history of type 1 diabetes mellitus
2. Substantial pre-existing neurological or psychiatric illness that would confound the neurological assessment or other outcome assessment
3. 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.
4. Pregnant or breast-feeding at the time of study entry
5. Other serious conditions that make the patient unlikely to survive 90 days
6. Inability to follow the protocol or return for the 90 day follow up
7. Renal dialysis (including hemo or peritoneal dialysis)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Neurological Emergencies Treatment Trials Network (NETT)

NETWORK

Sponsor Role collaborator

Medical University of South Carolina

OTHER

Sponsor Role collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

University of Virginia

OTHER

Sponsor Role lead

Responsible Party

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Karen C. Johnston

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Karen C Johnston, MD, MSc

Role: STUDY_CHAIR

University of Virginia

Christiana Hall, MD, MS

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern

Askiel Bruno, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Augusta University

Valerie Durkalski, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

William Barsan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Kevin Barrett, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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University of Arizona Medical Center - South Campus

Tucson, Arizona, United States

Site Status

University of Arizona

Tucson, Arizona, United States

Site Status

Long Beach Memorial Medical Center

Long Beach, California, United States

Site Status

Ronald Regan Medical Center

Los Angeles, California, United States

Site Status

San Francisco General Hospital

San Francisco, California, United States

Site Status

California Pacific Medical Center - Davies Campus

San Francisco, California, United States

Site Status

California Pacific Medical Center-Pacific Campus

San Francisco, California, United States

Site Status

UCSF Medical Center

San Francisco, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status

Jackson Memorial Hospital

Miami, Florida, United States

Site Status

Emory University Hospital - Midtown

Atlanta, Georgia, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

Grady Memorial Hospital

Atlanta, Georgia, United States

Site Status

Augusta University Medical Center

Augusta, Georgia, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Site Status

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

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Tufts Medical Center

Boston, Massachusetts, United States

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

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Detroit Receiving Hospital

Detroit, Michigan, United States

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Henry Ford Health System

Detroit, Michigan, United States

Site Status

Sinai-Grace Hospital

Detroit, Michigan, United States

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William Beaumont Hospital-Royal Oak

Royal Oak, Michigan, United States

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William Beaumont Hospital-Troy

Troy, Michigan, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, United States

Site Status

JFK Medical Center

Edison, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Kings County Hospital

Brooklyn, New York, United States

Site Status

SUNY Downstate University Hospital of Brooklyn

Brooklyn, New York, United States

Site Status

Buffalo General Medical Center

Buffalo, New York, United States

Site Status

The Mount Sinai Medical Center

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Weill Cornell Medical Center

New York, New York, United States

Site Status

Maimonides Medical Center

New York, New York, United States

Site Status

Lincoln Medical and Mental Health Center

The Bronx, New York, United States

Site Status

Summa Akron City Hospital

Akron, Ohio, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Wexner Medical Center

Columbus, Ohio, United States

Site Status

Miami Valley Hospital

Dayton, Ohio, United States

Site Status

Abington Memorial Hospital

Abington, Pennsylvania, United States

Site Status

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Presbyterian

Pittsburgh, Pennsylvania, United States

Site Status

UPMC - Mercy

Pittsburgh, Pennsylvania, United States

Site Status

WellSpan York Hospital

York, Pennsylvania, United States

Site Status

St. Thomas Neuroscience Research Institute

Nashville, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Dell Seton Medical Center at UT

Austin, Texas, United States

Site Status

Seton Medical Center

Austin, Texas, United States

Site Status

UT Southwestern-Parkland Memorial Hospital

Dallas, Texas, United States

Site Status

UT Southwestern-Zale Lipshy University Hospital

Dallas, Texas, United States

Site Status

Valley Baptist Medical Center

Harlingen, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Memorial Herman Hospital

Houston, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Harborview Medical Center

Seattle, Washington, United States

Site Status

West Virginia University

Morgantown, West Virginia, United States

Site Status

Froedtert Memorial Hospital

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Johnston KC, Bruno A, Pauls Q, Hall CE, Barrett KM, Barsan W, Fansler A, Van de Bruinhorst K, Janis S, Durkalski-Mauldin VL; Neurological Emergencies Treatment Trials Network and the SHINE Trial Investigators. Intensive vs Standard Treatment of Hyperglycemia and Functional Outcome in Patients With Acute Ischemic Stroke: The SHINE Randomized Clinical Trial. JAMA. 2019 Jul 23;322(4):326-335. doi: 10.1001/jama.2019.9346.

Reference Type RESULT
PMID: 31334795 (View on PubMed)

Southerland AM, Mayer SA, Chiota-McCollum NA, Bolte AC, Pauls Q, Pettigrew LC, Bleck TP, Conaway M, Johnston KC. Glucose Control and Risk of Symptomatic Intracerebral Hemorrhage Following Thrombolysis for Acute Ischemic Stroke: A SHINE Trial Analysis. Neurology. 2024 May 14;102(9):e209323. doi: 10.1212/WNL.0000000000209323. Epub 2024 Apr 16.

Reference Type DERIVED
PMID: 38626363 (View on PubMed)

Arteaga DF, Ulep R, Kumar KK, Southerland AM, Conaway MR, Faber J, Wintermark M, Joyner D, Sharashidze V, Hirsch K, Giurgiutiu DV, Hannawi Y, Aziz Y, Shutter L, Visweswaran A, Williams A, Williams K, Gunter S, Haughey HM, Bruno A, Johnston KC, Patel VN; SHINE Trial Investigators. Collateral status, hyperglycemia, and functional outcome after acute ischemic stroke. BMC Neurol. 2022 Nov 4;22(1):408. doi: 10.1186/s12883-022-02943-4.

Reference Type DERIVED
PMID: 36333676 (View on PubMed)

Connor JT, Broglio KR, Durkalski V, Meurer WJ, Johnston KC. The Stroke Hyperglycemia Insulin Network Effort (SHINE) trial: an adaptive trial design case study. Trials. 2015 Mar 4;16:72. doi: 10.1186/s13063-015-0574-8.

Reference Type DERIVED
PMID: 25885963 (View on PubMed)

Garofolo KM, Yeatts SD, Ramakrishnan V, Jauch EC, Johnston KC, Durkalski VL. The effect of covariate adjustment for baseline severity in acute stroke clinical trials with responder analysis outcomes. Trials. 2013 Apr 11;14:98. doi: 10.1186/1745-6215-14-98.

Reference Type DERIVED
PMID: 24499406 (View on PubMed)

Bruno A, Durkalski VL, Hall CE, Juneja R, Barsan WG, Janis S, Meurer WJ, Fansler A, Johnston KC; SHINE investigators. The Stroke Hyperglycemia Insulin Network Effort (SHINE) trial protocol: a randomized, blinded, efficacy trial of standard vs. intensive hyperglycemia management in acute stroke. Int J Stroke. 2014 Feb;9(2):246-51. doi: 10.1111/ijs.12045. Epub 2013 Mar 19.

Reference Type DERIVED
PMID: 23506245 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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U01NS069498

Identifier Type: NIH

Identifier Source: secondary_id

View Link

15959

Identifier Type: -

Identifier Source: org_study_id