Remote ischemic conditioning for safety, feasibility and preliminary efficacy of patients with aneurysmal subarachnoid hemorrhage after aneurysm clipping, design, and protocol for an open-label, evaluator blinding randomized controlled trial.

Background and rationale: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe cerebrovascular event with a high mortality and disability rate. Compared to interventional surgery, microsurgical clipping is more invasive and has a higher incidence of postoperative complications, including cerebral vasospasm and ischemic cerebral infarction. In recent years, a large number of basic experiments have proved that remote ischemic conditioning (RIC) has multiple pathways of neuroprotective effects, and many large-scale randomized controlled clinical trials have confirmed that remote ischemic conditioning applied to patients with ischemic stroke has the effect of improving prognosis. However, current research has only focused on demonstrating the safety of remote ischemic conditioning for patients with aSAH, and lacks high-level evidence for its effectiveness. Method: We design an open-label, evaluator blinding randomized controlled trial. This study focuses on aneurysmal subarachnoid hemorrhage occurring within 24 h after microsurgical clipping. All participants will be randomly assigned to the intervention group and the control group at a 1:1 ratio (n = 20), and will receive standard management according to the guidelines. Participants assigned to the intervention group will receive RIC twice a day, once in the morning and once in the afternoon, for 7 consecutive days after the operation. Neurological prognosis will be evaluated at baseline, day 3, day 7, day 30, and day 90. The primary outcome measure is the proportion of patients with a mRS score of 0-2 at 90 ± 7 days after surgery and the incidence rate of RIC adverse events. The secondary measures include the incidence of aSAH complications, the mRS score of patients 30 ± 7 days after surgery, and the mRS score of patients 7 ± 1 day after surgery. Discussion: The study's aim is to explore the safety, feasibility and preliminary efficacy of RIC in aSAH patients after clipping surgery. It serves as a methodological and feasibility foundation for the later multicenter, double-blind REPAIR trial (NCT06711302), which aims to confirm efficacy in a larger population. Clinical trial registration: https://clinicaltrials.gov/study/NCT06819657?term=NCT06819657&rank=1, NCT06819657.