Rationale and Study Design for a Single-Arm Phase IIa Study Investigating Feasibility of Preventing Ischemic Cerebrovascular Events in High-Risk Patients with Acute Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning

Abstract

Background:Acute minor ischemic stroke (AMIS) or transient ischemic attack (TIA) is a common cerebrovascular event with a considerable high recurrence. Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning (RIC) in secondary stroke prevention in patients with intracranial stenosis. We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA. This study aimed to investigate the feasibility, safety, and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA.Methods:This is a single-arm, open-label, multicenter Phase IIa futility study with a sample size of 165. Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen. RIC consists of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days. The antiplatelet strategy is based on individual physician's best practice: aspirin alone, clopidogrel alone, or combination of aspirin and clopidogrel. We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes.Conclusions:The data gathered from the study will be used to determine whether a further large-scale, multicenter randomized controlled Phase II trial is warranted in patients with AMIS/TIA.Trial Registration:ClinicalTrials.gov, NCT03004820; https://www.clinicaltrials.gov/ct2/show/NCT03004820.

Preventing Ischemic Cerebrovascular Events in High-Risk Patients With Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning: A Single-Arm Study

“…A team of researchers from Xuanwu Hospital of the Capital Medical University (China) and the Medical University of South Carolina (USA) designed this study. A detailed rationale and study design of the Preventing Ischemic Cerebrovascular events in patients with acute Non-disabling Ischemic Cerebrovascular events using RIC (PICINIC-One) study was published previously ( 14 ). This study was conducted at four sites in China: Xuanwu Hospital of Capital Medical University, Shengli Oilfield Center Hospital, the First Affiliated Hospital of Hainan Medical University, and Taoyuan People's Hospital.…”

“…The null hypothesis was that the recurrence rate of ischemic stroke/TIA within 3 months would be greater than the largest regression probability of recurrence ( P 0 = 12%). The alternative hypothesis was that the recurrence rate of ischemic stroke/TIA within 3 months would be less than the smallest regression probability of recurrence ( P A = 6%) ( 14 ). To test our hypothesis, with an assumption of a type 1 error of 5%, a power of 80%, and an attrition rate of 10%, the sample size was estimated to be 165 ( 15 ).…”

Remote but not Distant: a Review on Experimental Models and Clinical Trials in Remote Ischemic Conditioning as Potential Therapy in Ischemic Stroke

“…In fact, one may speculate that remote conditioning triggers mild responses by the organism, which would need chronic application for generating beneficial effects. Accordingly, Liu and colleagues have described a protocol, which is ongoing and only includes patients with acute minor ischemic stroke or transient ischemic attack [ 118 ]. In this clinical trial, RIC is used as adjuvant treatment for secondary stroke prevention.…”