Arterial Glyceryl Trinitrate in Acute Ischemic Stroke after Thrombectomy for Neuroprotection (AGAIN): Rationale, design and protocol for a prospective randomized controlled trial

Abstract

BackgroundAlthough endovascular recanalization therapy demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all victims of these cerebrovascular accidents can benefit from it and achieve a favorable prognosis after successful reperfusion. Therefore, alternative neuroprotective strategies are urgently needed for AIS patients after vessel recanalization. Nitric oxide (NO) levels are low after AIS and NO donor drugs may be neuroprotective against cerebral ischemia–reperfusion injury. Glyceryl trinitrate (GTN), often used in the clinic as a NO donor, may provide a novel neuroprotective strategy. This rationale, design, and protocol for a prospective pilot study plans to explore the preliminary safety, feasibility, and neuroprotective benefits of Arterial Glyceryl Trinitrate in Acute Ischemic Stroke after Thrombectomy for Neuroprotection (AGAIN).MethodsAGAIN, a prospective RCT, is proposed for AIS patients after mechanical thrombectomy. Subjects will be randomly assigned in a 1:1 fashion (n = 40) to either the control group or the intervention group. Participants assigned to the intervention group will be administered 800 μg GTN in the catheter immediately after recanalization, whereas those in the control group will be administered the same volume of normal saline. All participants from either group will be given concurrent treatment with standard of care therapies in accordance with the current guidelines for stroke management. The primary outcome is safety [symptomatic intracranial hemorrhage (ICH), hypotension, neurological deterioration, ICH, fatal ICH, as well as headache, tachycardia, emesis, and seizures], whereas secondary outcomes included changes in poststroke functional outcomes, infarction volumes, and blood nitrate index detection.DiscussionsThis study is a prospective randomized controlled trial to test the safety and efficacy of intra-arterial GTN in AIS patients after endovascular therapy. The results from this study will give insight for future GTN studies and new neuroprotective strategies for future AIS treatment strategies.Trial registration numberChiCTR2100045254. Registered on March 21, 2021.