Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial

NCT01369069 | Completed Phase 3 Results DMC

• 2 other identifiers: 15959U01NS069498
• Study Type: interventional
• Target: 1,151
• Locations: 1 country
• Sites: 70

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.

Conditions

Acute Ischemic Stroke; Diabetes; Hyperglycemia

Keywords

stroke; diabetes; hyperglycemia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Number of Participants With a Favorable NIHSS

  Follow up (Max 164 days)

• Number of Participants With a Favorable Barthel Index

  Follow up (Max 164 days)

• Stroke Specific Quality of Life (SSQOL)

  Follow up (Max 164 days)

Other Outcomes (1)

• Death

  90 days (+30 days)

Study Arms (2)

IV insulin drip with target glucose 80 mg/dL - 130 mg/dL

EXPERIMENTAL

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

Sub Q insulin to keep glucose less than 180 mg/dL

ACTIVE COMPARATOR

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

Interventions

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

Also known as: Continuous intravenous insulin

IV insulin drip with target glucose 80 mg/dL - 130 mg/dL

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

Also known as: Sliding scale insulin

Sub Q insulin to keep glucose less than 180 mg/dL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Virginia: lead
• Neurological Emergencies Treatment Trials Network (NETT): collaborator
• Medical University of South Carolina: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (70)

University of Arizona Medical Center - South Campus

Tucson, Arizona, 85713, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Ronald Regan Medical Center

Los Angeles, California, 90095, United States

Location

San Francisco General Hospital

San Francisco, California, 94110, United States

Location

California Pacific Medical Center - Davies Campus

San Francisco, California, 94114, United States

Location

California Pacific Medical Center-Pacific Campus

San Francisco, California, 94114, United States

Location

UCSF Medical Center

San Francisco, California, 94117, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Emory University Hospital - Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30322, United States

Location

Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kentucky

Lexington, Kentucky, 40506, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Sinai-Grace Hospital

Detroit, Michigan, 48235, United States

Location

William Beaumont Hospital-Royal Oak

Royal Oak, Michigan, 48073, United States

Location

William Beaumont Hospital-Troy

Troy, Michigan, 48085, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, 55455, United States

Location

JFK Medical Center

Edison, New Jersey, 08818, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Kings County Hospital

Brooklyn, New York, 11203, United States

Location

SUNY Downstate University Hospital of Brooklyn

Brooklyn, New York, 11203, United States

Location

Buffalo General Medical Center

Buffalo, New York, 14210, United States

Location

The Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Maimonides Medical Center

New York, New York, 11219, United States

Location

Lincoln Medical and Mental Health Center

The Bronx, New York, 10451, United States

Location

Summa Akron City Hospital

Akron, Ohio, 44307, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45221, United States

Location

Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19102, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UPMC Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC - Mercy

Pittsburgh, Pennsylvania, 15219, United States

Location

WellSpan York Hospital

York, Pennsylvania, 17403, United States

Location

St. Thomas Neuroscience Research Institute

Nashville, Tennessee, 37205, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Dell Seton Medical Center at UT

Austin, Texas, 78701, United States

Location

Seton Medical Center

Austin, Texas, 78705, United States

Location

UT Southwestern-Parkland Memorial Hospital

Dallas, Texas, 75390, United States

Location

UT Southwestern-Zale Lipshy University Hospital

Dallas, Texas, 75390, United States

Location

Valley Baptist Medical Center

Harlingen, Texas, 78552, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Memorial Herman Hospital

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Froedtert Memorial Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (6)

• 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.

  PMID: 31334795 RESULT

• 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.

  PMID: 38626363 DERIVED

• 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.

  PMID: 36333676 DERIVED

• 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.

  PMID: 25885963 DERIVED

• 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.

  PMID: 24499406 DERIVED

• 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.

  PMID: 23506245 DERIVED

Related Links

• General information of trial

MeSH Terms

Conditions

Ischemic Stroke; Diabetes Mellitus; Hyperglycemia; Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Karen C. Johnston, MD
• Organization: University of Virginia

kj4v@virginia.edu

434 924-5323

Study Officials

• Karen C Johnston, MD, MSc

  University of Virginia

  STUDY CHAIR

• Christiana Hall, MD, MS

  UT Southwestern

  PRINCIPAL INVESTIGATOR

• Askiel Bruno, MD, MS

  Augusta University

  PRINCIPAL INVESTIGATOR

• Valerie Durkalski, PhD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

• William Barsan, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Kevin Barrett, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 6, 2011
• First Posted: June 8, 2011
• Study Start: April 1, 2012
• Primary Completion: November 19, 2018
• Study Completion: November 19, 2018
• Last Updated: December 23, 2019
• Results First Posted: December 16, 2019

Record last verified: 2019-12

Locations

US (70)