There is an increasing need for improved treatments for stroke patients as stroke is a common, devastating and extremely costly disease to the health care system. Forty percent of acute ischemic stroke patients are hyperglycemic upon arrival to the hospital. Hyperglycemia is associated with worse clinical outcome but it is unclear if tight glucose control can improve outcome. Severe or prolonged hypoglycemia can also be very damaging to ischemic brain. Clinical equipoise exists and current American Heart Association Guidelines encourage clinical trials to provide evidence on how to treat hyperglycemic acute stroke patients. The SHINE Trial is a multicenter, randomized, single blind (double blind outcomes) Phase III trial of 1400 patients at 56 sites across the United States. Patients will be randomized to IV insulin with tight glucose control (80-130 mg/dL) versus standard sliding scale subcutaneous insulin (<180 mg/dL). The primary outcome will be a severity adjusted dichotomized modified Rankin score (mRS) (responder analysis).
The specific aims for this trial are: 'Specific Aim 1: To determine the efficacy of tight glucose control to a target range of 80-130 mg/dL with IV insulin infusion in hyperglycemic acute ischemic stroke patients within 12 hours of symptom onset (and 3 hours of arrival to ED) as measured by mRS at 90 days after stroke. Hypothesis 1: Tight glucose control (target 80-130 mg/dL) with IV insulin infusion therapy using eProtocol-insulin, a validated computerized decision support tool, will increase the severity adjusted 90 day favorable outcome on the mRS by an absolute 7% or more, as compared to the control group.
Specific Aim 2 : To determine the safety of tight glucose control with IV insulin infusion in hyperglycemic acute ischemic stroke patients treated for up to 72 hrs. Hypothesis 2: Tight glucose control with IV insulin infusion therapy using eProtocol-insulin is safe as determined by a severe hypoglycemia rate (<40 mg/dL) of less than 4%.

Public Health Relevance

Stroke is the most common cause of adult disability and the third most common cause of death in the U.S. Forty percent of acute ischemic stroke patients are hyperglycemic and hyperglycemia is associated with worse clinical outcome but clinicians do not have data on how to manage the hyperglycemia. The SHINE trial is a Phase III efficacy and safety trial of glycemic control and the results will guide clinical practice all over the nation and the world.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZNS1-SRB-R (48))
Program Officer
Mcneil, Dawn E
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Virginia
Schools of Medicine
United States
Zip Code
Jha, Ruchira M; Puccio, Ava M; Chou, Sherry Hsiang-Yi et al. (2017) Sulfonylurea Receptor-1: A Novel Biomarker for Cerebral Edema in Severe Traumatic Brain Injury. Crit Care Med 45:e255-e264
Jha, Ruchira M; Puccio, Ava M; Okonkwo, David O et al. (2017) ABCC8 Single Nucleotide Polymorphisms are Associated with Cerebral Edema in Severe TBI. Neurocrit Care 26:213-224
Jiang, Yunyun; Zhao, Wenle; Durkalski-Mauldin, Valerie (2017) Impact of adaptation algorithm, timing, and stopping boundaries on the performance of Bayesian response adaptive randomization in confirmative trials with a binary endpoint. Contemp Clin Trials 62:114-120
Southerland, Andrew M (2017) Clinical Evaluation of the Patient With Acute Stroke. Continuum (Minneap Minn) 23:40-61
Southerland, Andrew M; Johnston, Karen C; Molina, Carlos A et al. (2016) Suspected Large Vessel Occlusion: Should Emergency Medical Services Transport to the Nearest Primary Stroke Center or Bypass to a Comprehensive Stroke Center With Endovascular Capabilities? Stroke 47:1965-7
Connor, Jason T; Broglio, Kristine R; Durkalski, Valerie et al. (2015) The Stroke Hyperglycemia Insulin Network Effort (SHINE) trial: an adaptive trial design case study. Trials 16:72
Zhao, Wenle; Durkalski, Valerie (2014) Managing competing demands in the implementation of response-adaptive randomization in a large multicenter phase III acute stroke trial. Stat Med 33:4043-52
Bruno, Askiel; Durkalski, Valerie L; Hall, Christiana E et al. (2014) 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 9:246-51
Garofolo, Kyra M; Yeatts, Sharon D; Ramakrishnan, Viswanathan et al. (2013) The effect of covariate adjustment for baseline severity in acute stroke clinical trials with responder analysis outcomes. Trials 14:98
Johnston, S Claiborne; Easton, J Donald; Farrant, Mary et al. (2013) Platelet-oriented inhibition in new TIA and minor ischemic stroke (POINT) trial: rationale and design. Int J Stroke 8:479-83

Showing the most recent 10 out of 11 publications