At a Glance
- Hyperglycemia is common in patients with acute ischemic stroke and is associated with worse outcomes compared with normal blood sugar levels.
- The recently published Stroke Hyperglycemia Insulin Network Effort (SHINE) study was designed to test the efficacy and safety of intense glucose control in ischemic stroke patients within 12 hours of symptom onset.
- Study results confirm that aggressive methods to control glucose in this patient population are not better than standard approaches.
Patients with hyperglycemia have poorer outcomes after an acute stroke. However, according to UVA neurologist and associate vice president of clinical and translational research Karen Johnston, MD, there’s always been a lot of uncertainty about how best to manage elevated glucose levels in these patients.
Too aggressive a treatment may lead to hypoglycemia, which negatively impacts the brain. But a more hands-off approach may jeopardize stroke recovery. The Stroke Hyperglycemia Insulin Network Effort (SHINE) trial, funded by the National Institutes of Health and led by Johnston, the study’s principle investigator, was initiated in 2012 to clarify the best treatment approach. “The SHINE trial was trying to address this worldwide debate about how we should treat hyperglycemia after an acute stroke,” she says. “We know that high glucose in the acute stroke period is associated with worse outcomes. Some people think we should treat it aggressively with intensive treatment like IV insulin to tightly control glucose. Others think we shouldn’t do that because it’s too risky. That’s exactly the question that the SHINE trial was trying to answer.”
About SHINE
Seventy sites across the country participated in the SHINE study, which was designed to test the efficacy and safety of intense glucose control in ischemic stroke patients within 12 hours of symptom onset. Patients were divided into two groups.
- The intensive group received an insulin drip, with a target glucose of 80 to 130 mg/dl.
- The standard group received sliding-scale insulin, with a target glucose of 80 to 179 mg/dl.
The study had a maximum enrollment allotment of 1,400 patients. “We built in several preplanned interim analyses that would allow us to consider whether we needed that many patients,” says Johnston.
These analyses allowed study leaders to take a regular look at futility, when two groups look so similar that it’s unlikely one will be better than the other, as well as efficacy. “If one group was doing much better — or if both groups were doing the same — then we could stop early,” explains Johnston.
At the fourth interim analysis, the two study groups looked essentially the same when it came to efficacy. “With 1,151 patients enrolled, the intensive group had 20.5% of patients that had a favorable outcome and the standard group had 21.6% of patients with a favorable outcome, so there was no significant difference,” says Johnston.
As study leaders took a closer look at safety outcomes, however, they did find a notable difference. In the intensive group, 2.6% of patients had severe hypoglycemia (defined as ≤ 40 mg/dl). In the standard group, there were none. “This confirmed that there was no benefit to tightly controlling glucose, but there was an increased risk,” says Johnston.
Redefining Glucose Control Post-Stroke
Because of the SHINE study, stroke providers worldwide now have a clear set of parameters for effective glucose management in acute stroke patients. “Prior to the SHINE study, we identified huge variability across the country and across the world. Some providers were putting everyone on these aggressive insulin drips to try to tightly control glucose. Others were afraid to treat glucose for fear of causing hypoglycemia,” says Johnston. “Now we have clarified the fact that treating these patients with an insulin drip does not improve their outcome and it increases the risk of hypoglycemia.”
The takeaway: the American Heart Association-recommended guideline suggests that it is reasonable to keep glucose between 140-180 mg/dL in the first 24 hours after stroke. However, the AHA has acknowledged that this is not a strong recommendation because of the limited data and lack of adequate evidence from a randomized controlled trial. Until now.
“The SHINE trial now provides that evidence to allow for a clear recommendation about glucose control without concern for severe hypoglycemia,” says Johnston.
“I think this study will reduce the variability in how we treat patients, and it will give provides the confidence to treat glucose based on the evidence,” says Johnston. Watch the video below to hear Johnston discuss the impact of the SHINE study.
Teaming Up to Shape the Future of Stroke Care
Only around 3% of hospitals across the country achieve the Joint Commission Comprehensive Stroke Center status. The UVA Stroke Center is one of them. In addition to its level of clinical expertise, rapid stroke response, telemedicine capabilities and top-notch rehabilitative care, UVA has been a pioneer in advancing stroke care for decades through clinical trials. The SHINE study is one more example of just how broad the reach of the UVA stroke team.
“UVA is a leader in the field of acute stroke and acute stroke clinical trials,” says Johnston. “We are part of the NIH-NINDS [National Institute of Neurological Disorders and Stroke] StrokeNet, which is a network of the major academic stroke programs around the country. This allows us to participate in all types of stroke trials as part of team science. These team-based research programs allow experts from all over the country to come together and share their expertise to produce a higher level of research success. I’m a big fan of this team approach; it facilitates synergy and elevates research to another level.”
The SHINE trial engaged leaders and teams from across the country with a shared leadership structure, which clearly contributed to the success of the program,” adds Johnston. “Being one of only a small number of NIH-NINDS funded phase 3 clinical trials in acute stroke is quite an honor and quite a responsibility. I am proud that as a team we have clearly and efficiently answered the question the NIH funded us to answer. We are fortunate at UVA to have an expert stroke team to lead such a national effort.“
UVA offers additional research programs that provide opportunities for stroke patients to participate in cutting-edge research if they choose. See a complete list of stroke trials at UVA.