| Summary: | Abstract Background Recent findings on the benefits of glibenclamide as a neuroprotective drug have started a new era for prospective studies on sulfonylureas. The effect of glibenclamide blocking the Sur1-Trpm4 channel was examined in models of subarachnoid hemorrhage and stroke, with findings of significantly reduced tight-junction abnormalities, resulting in less edema formation and considerably reduced transsynaptic apoptosis of hippocampal neurons and significantly ameliorated impairments in spatial learning. Based on these data, we plan a clinical trial to establish evidence of glibenclamide as an adjunct treatment in aneurysmal subarachnoid hemorrhage. Methods An estimated 80 patients meeting the inclusion criteria of radiological confirmatory evidence of an aneurysmal subarachnoid hemorrhage, age 18–70 years, and presentation of less than 96 h from the ictus will be allocated randomly into two groups, one receiving 5 mg daily oral intake of glibenclamide for 21 days and another control group receiving a placebo. The study’s primary outcome is the modified Rankin scale (mRS) after 6 months, as favorable (mRS 0–2) or unfavorable (mRS 3–6). The secondary outcomes will be late cognitive status, assessed after 6 months by psychological tests (the Short Form Health Survey Questionnaire and the Montreal Cognitive Assessment), as well as death at 6 months, delayed cerebral ischemia and occurrence of serious adverse events due to study medication. Discussion There is a growing interest in the scientific community regarding glibenclamide in brain edema and traumatic brain injury, but with very little of this interest targeting spontaneous brain hemorrhage, especially aneurism rupture. Positive outcomes are expected for the treatment patients, especially in language and memory preservation, as has been shown in experimental models. Trial registration ClinicalTrials.gov, NCT03569540. Retrospectively registered on 26 June 2018.
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