Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): study protocol for a randomized controlled trial

BMC Neurol. 2020 Jun 11;20(1):239. doi: 10.1186/s12883-020-01823-z.

Abstract

Background: Thrombolysis with recombinant tissue plasminogen activator (rtPA) improves outcome for patients with acute ischemic stroke (AIS), but many of them still have substantial disability. Glibenclamide (US adopted name, glyburide), a long-acting sulfonylurea, shows promising result in treating AIS from both preclinical and clinical studies. This study investigates the safety and efficacy of glibenclamide combined with rtPA in treating AIS patients.

Methods: This is a prospective, randomized, double-blind, placebo-controlled, multicenter trial with an estimated sample size of 306 cases, starting in January 2018. Patients aged 18 to 74 years, presented with a symptomatic anterior circulation occlusion with a deficit on the NIHSS of 4 to 25 points and treated with intravenous rtPA within the first 4.5 h of their clinical onsets, are eligible for participation in this study. The target time from the onset of symptoms to receive the study drug is of 10 h. Subjects are randomized 1: 1 to receive glibenclamide or placebo with a loading dose of 1.25 mg, followed by 0.625 mg every 8 h for total 5 days. The primary efficacy endpoint is 90-day good outcome, measured as modified Rankin Scale of 0 to 2. Safety outcomes are all-cause 30-day mortality and early neurological deterioration, with a focus on cardiac- and glucose-related serious adverse events.

Discussion: This study will provide valuable information about the safety and efficacy of oral glibenclamide for AIS patients treated with rtPA. This would bring benefits to a large number of patients if the agent is proved to be effective.

Trial registration: The trial was registered on September 14th 2017 at www.clinicaltrials.gov having identifier NCT03284463. Registration was performed before recruitment was initiated.

Keywords: Combined treatment; Glibenclamide; Randomized controlled trial; Stroke.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brain Ischemia / complications
  • Constriction, Pathologic
  • Double-Blind Method
  • Female
  • Fibrinolytic Agents / therapeutic use
  • Glyburide / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Prospective Studies
  • Randomized Controlled Trials as Topic*
  • Stroke / drug therapy*
  • Stroke / etiology
  • Tissue Plasminogen Activator / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Fibrinolytic Agents
  • Tissue Plasminogen Activator
  • Glyburide

Associated data

  • ClinicalTrials.gov/NCT03284463