RESUMEN
OBJECTIVE: Glibenclamide has been shown to improve outcomes in cerebral ischemia, traumatic brain injury, and subarachnoid hemorrhage (SAH). The authors sought to evaluate glibenclamide's impact on mortality and functional outcomes of patients with aneurysmal SAH (aSAH). METHODS: Patients with radiologically confirmed aSAH, aged 18 to 70 years, who presented to the hospital within 96 hours of ictus were randomly allocated to receive 5 mg of oral glibenclamide for 21 days or placebo, in a modified intention-to-treat analysis. Outcomes were mortality and functional status at discharge and 6 months, evaluated using the modified Rankin Scale (mRS). RESULTS: A total of 78 patients were randomized and allocated to glibenclamide (n = 38) or placebo (n = 40). Baseline characteristics were similar between groups. The mean patient age was 53.1 years, and the majority of patients were female (75.6%). The median Hunt and Hess, World Federation of Neurosurgical Societies (WFNS), and modified Fisher scale (mFS) scores were 3 (IQR 2-4), 3 (IQR 3-4), and 3 (IQR 1-4), respectively. Glibenclamide did not improve the functional outcome (mRS) after 6 months (ordinal analysis, unadjusted common OR 0.66 [95% CI 0.29-1.48], adjusted common OR 1.25 [95% CI 0.46-3.37]). Similar results were found for analyses considering the dichotomized 6-month mRS score (favorable score 0-2), as well as for the secondary outcomes of discharge mRS score (either ordinal or dichotomized), mortality, and delayed cerebral ischemia. Hypoglycemia was more frequently observed in the glibenclamide group (5.3%). CONCLUSIONS: In this study, glibenclamide was not associated with better functional outcomes after aSAH. Mortality and delayed cerebral ischemia rates were also similar compared with placebo.
RESUMEN
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.
