HONOLULU -- Intensive early management of glucose with a target of 80-130 mg/dL using IV insulin after ischemic stroke did not improve outcomes but carried a higher severe hypoglycemia risk, the randomized SHINE trial showed.
Good functional outcome by 90-day modified Rankin scale (mRS) score adjusted for stroke severity was actually numerically more common with standard management of glucose to under 180 mg/dL with subcutaneous insulin in the first 12 hours of symptom onset (21.6% vs 20.5%, P=0.55).
Severe hypoglycemia occurred in 2.6% of intensively managed patients compared with none of the standard therapy group (risk difference 2.58, 95% CI 1.29-3.87), Karen Johnston, MD, of the University of Virginia in Charlottesville, reported here at the American Heart Association's International Stroke Conference.
The preferred glucose management strategy in acute stroke should be subcutaneous insulin with a target of under 180 mg/dL, Johnston concluded at the session, noting that the prior GIST-UK trial and two middle-phase trials suggesting safety had been underpowered.
"That trial answers a lot of unanswered questions," late-breaking clinical trial session moderator Louise McCullough, MD, PhD, of the University of Texas Health Science Center at Houston, told attendees.
Indeed, “hyperglycemia is common in acute stroke patients, and it’s linked to worse functional outcomes when compared with euglycemic stroke patients,” commented Miguel Perez-Pinzon, PhD, of the University of Miami and conference program committee chair.
“In clinical trials, the most important thing at the end is to have an unambiguous result… Sadly it’s negative, but there’s no doubt,” said Patrick Lyden, MD, of Cedars-Sinai Medical Center in Los Angeles.
“There’s a backstory, this is not the first glucose management trial,” he told MedPage Today. “Given the fact that you’ve got mixed messages coming to today and now you have a very clear answer. I personally wouldn’t want to mount another trial.”
It’s good news in a way, because standard therapy is less burdensome for nursing and other team members, Lyden noted.
Indeed, "hyperglycemia is common in acute stroke patients, and it's linked to worse functional outcomes when compared with euglycemic stroke patients," commented Miguel Perez-Pinzon, PhD, of the University of Miami and conference program committee chair.
Before the NIH-funded trial was stopped for futility, it included 1,151 patients with type 2 diabetes who either had glucose over 110 mg/dL at randomization (80%) or no known diabetes but a baseline glucose level of at least 150 mg/dL. Randomization was within 12 hours of symptom onset. Type 1 diabetes and dialysis patients were excluded.
Median baseline glucose was 188 mg/dL. Both groups quickly got to glucose target and maintained separation with an average 118 mg/dL in the intensive group and 179 mg/dL with standard management.
Criteria for favorable outcome were a 0 mRS if initial stroke severity was 3 to 7 on the NIHSS scale, 1 or less if NIHSS was 8 to 14, or up to 2 if NIHSS was 15 to 22. Average stroke severity was 7.
Treatment was single blind.
No differences in additional outcomes such as NIHSS of 0 or 1, stroke-related quality of life, and favorable Barthel Index were seen.
The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS) of NIH.
Medical Decision Network provided the GlucoStabilizer, a computer decision support tool, at no cost.
Johnston disclosed relationships with the NINDS (Council), FDA (panel), ANA, AAN, AUPN, Biogen, and Diffusion Pharmaceuticals.
Lyden disclosed no relevant relationships with industry.
Intensive Early Glucose Control No Help for Stroke Recovery
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