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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

Date

07/25/2019

Pubmed ID

31334795

Pubmed Central ID

PMC6652154

DOI

10.1001/jama.2019.9346

Scopus ID

2-s2.0-85069770209 (requires institutional sign-in at Scopus site)   243 Citations

Abstract

IMPORTANCE: Hyperglycemia during acute ischemic stroke is common and is associated with worse outcomes. The efficacy of intensive treatment of hyperglycemia in this setting remains unknown.

OBJECTIVES: To determine the efficacy of intensive treatment of hyperglycemia during acute ischemic stroke.

DESIGN, SETTING, AND PARTICIPANTS: The Stroke Hyperglycemia Insulin Network Effort (SHINE) randomized clinical trial included adult patients with hyperglycemia (glucose concentration of >110 mg/dL if had diabetes or ≥150 mg/dL if did not have diabetes) and acute ischemic stroke who were enrolled within 12 hours from stroke onset at 63 US sites between April 2012 and August 2018; follow-up ended in November 2018. The trial included 1151 patients who met eligibility criteria.

INTERVENTIONS: Patients were randomized to receive continuous intravenous insulin using a computerized decision support tool (target blood glucose concentration of 80-130 mg/dL [4.4-7.2 mmol/L]; intensive treatment group: n = 581) or insulin on a sliding scale that was administered subcutaneously (target blood glucose concentration of 80-179 mg/dL [4.4-9.9 mmol/L]; standard treatment group: n = 570) for up to 72 hours.

MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the proportion of patients with a favorable outcome based on the 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) that was adjusted for baseline stroke severity.

RESULTS: Among 1151 patients who were randomized (mean age, 66 years [SD, 13.1 years]; 529 [46%] women, 920 [80%] with diabetes), 1118 (97%) completed the trial. Enrollment was stopped for futility based on prespecified interim analysis criteria. During treatment, the mean blood glucose level was 118 mg/dL (6.6 mmol/L) in the intensive treatment group and 179 mg/dL (9.9 mmol/L) in the standard treatment group. A favorable outcome occurred in 119 of 581 patients (20.5%) in the intensive treatment group and in 123 of 570 patients (21.6%) in the standard treatment group (adjusted relative risk, 0.97 [95% CI, 0.87 to 1.08], P = .55; unadjusted risk difference, -0.83% [95% CI, -5.72% to 4.06%]). Treatment was stopped early for hypoglycemia or other adverse events in 65 of 581 patients (11.2%) in the intensive treatment group and in 18 of 570 patients (3.2%) in the standard treatment group. Severe hypoglycemia occurred only among patients in the intensive treatment group (15/581 [2.6%]; risk difference, 2.58% [95% CI, 1.29% to 3.87%]).

CONCLUSIONS AND RELEVANCE: Among patients with acute ischemic stroke and hyperglycemia, treatment with intensive vs standard glucose control for up to 72 hours did not result in a significant difference in favorable functional outcome at 90 days. These findings do not support using intensive glucose control in this setting.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01369069.

Author List

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

Author

Marc A. Lazzaro MD Associate Professor in the Neurology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Brain Ischemia
Female
Fibrinolytic Agents
Humans
Hyperglycemia
Hypoglycemia
Hypoglycemic Agents
Infusions, Intravenous
Injections, Subcutaneous
Insulin
Male
Middle Aged
Stroke
Tissue Plasminogen Activator
Treatment Outcome