Trial of EXenatide in Acute Ischaemic Stroke

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Elevated blood glucose levels are common in many acute diseases, resulting in worse clinical outcomes for patients. Hyperglycaemia in acute ischaemic stroke (post-stroke hyperglycaemia [PSH]) occurs in up to 50% patients, reduces the efficacy of stroke thrombolysis with increased risk of haemorrhage, increases infarct size, and results in worse clinical outcomes and death. Insulin-based therapies have not proved beneficial in treating PSH: they are difficult to implement and maintain, cause frequent hypoglycaemia, may cause increased infarct size, and have not shown to reduce mortality or improve clinical outcomes. An alternative, simple to use treatment for PSH may therefore have a significant impact not only for acute stroke care, but in other acute diseases. Exenatide is a commonly used diabetes drug (a synthetic glucagon-like peptide-1 receptor agonist) that amongst its effects increases insulin secretion. Importantly, this action is glucose dependent - as blood glucose levels decrease, its stimulatory effect on insulin secretion subsides, with a very low risk of hypoglycaemia. A previous pilot study of 17 consecutive, unselected patients (i.e. regardless of their admission glucose level) with acute ischaemic stroke compared subcutaneous Exenatide 5 micrograms for 5 days versus routine standard care. Blood glucose levels remained consistently lower (and less variable) in the treatment group, most noticeably in those stroke patients with known diabetes. Exenatide was safe and well tolerated by all patients, with no symptomatic hypoglycaemia. TEXAIS is a 3 year Phase 2, multi-centre, prospective, randomised, open label, blinded end-point trial comparing subcutaneous Exenatide (5 micrograms) to Standard of Care. The number of patients to be recruited is 528 patients (264 in each arm) with a primary end point of early neurological improvement at 7 days, and secondary end points of recovery at 90 days. Continuous glucose monitors will track the intra-day dynamic variability of glucose in acute stroke in all trial patients (treatment and standard care).