Clinical trial NCT01369069: Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial
Official title: Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Diabetes
Hyperglycemia
Keywords: stroke
diabetes
hyperglycemia
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: Neurological Emergencies Treatment Trials Network (NETT)
name: Medical University of South Carolina
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2011-06-08
Enrollment: 1151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants With a Favorable Modified Rankin Scale (Yes/No)
timeFrame: 90 days (-14/+30 days)
measure: Number of Participants With Severe Hypoglycemia (Blood Glucose < 40mg/dL)
timeFrame: 72 hours
Secondary outcomes:
measure: Number of Participants With a Favorable NIHSS
timeFrame: Follow up (Max 164 days)
measure: Number of Participants With a Favorable Barthel Index
timeFrame: Follow up (Max 164 days)
measure: Stroke Specific Quality of Life (SSQOL)
timeFrame: Follow up (Max 164 days)
Other outcomes:
measure: Death
timeFrame: 90 days (+30 days)
Locations:
city: Tucson
country: United States
facility: University of Arizona Medical Center - South Campus
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: Ronald Regan Medical Center
state: California
city: San Francisco
country: United States
facility: San Francisco General Hospital
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center - Davies Campus
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center-Pacific Campus
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Detroit Receiving Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Detroit
country: United States
facility: Sinai-Grace Hospital
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital-Royal Oak
state: Michigan
city: Troy
country: United States
facility: William Beaumont Hospital-Troy
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center, Fairview
state: Minnesota
city: Edison
country: United States
facility: JFK Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Lincoln Medical and Mental Health Center
state: New York
city: Brooklyn
country: United States
facility: Kings County Hospital
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate University Hospital of Brooklyn
state: New York
city: Buffalo
country: United States
facility: Buffalo General Medical Center
state: New York
city: New York
country: United States
facility: The Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: New York
country: United States
facility: Maimonides Medical Center
state: New York
city: Akron
country: United States
facility: Summa Akron City Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Wexner Medical Center
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC - Mercy
state: Pennsylvania
city: York
country: United States
facility: WellSpan York Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: St. Thomas Neuroscience Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Dell Seton Medical Center at UT
state: Texas
city: Austin
country: United States
facility: Seton Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern-Parkland Memorial Hospital
state: Texas
city: Dallas
country: United States
facility: UT Southwestern-Zale Lipshy University Hospital
state: Texas
city: Harlingen
country: United States
facility: Valley Baptist Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Memorial Herman Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Milwaukee
country: United States
facility: Froedtert Memorial Hospital
state: Wisconsin
Study officials:
affiliation: University of Virginia
name: Karen C Johnston, MD, MSc
role: STUDY_CHAIR
affiliation: UT Southwestern
name: Christiana Hall, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Augusta University
name: Askiel Bruno, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: Valerie Durkalski, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: William Barsan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Kevin Barrett, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.