Ischemic post-conditioning in acute ischemic stroke thrombectomy: A phase-I duration escalation study

Abstract

Background: Previous experimental studies have found that ischemic post-conditioning exhibits neuroprotective effects by alleviating ischemia-reperfusion injury in an acute ischemic stroke model, and its efficacy is thought to be related to the duration of ischemic post-conditioning. However, ischemic post-conditioning has not been used in patients with acute ischemic stroke. This study aims to determine the safety, tolerability, and maximum tolerable duration of ischemic post-conditioning in patients with acute ischemic stroke receiving mechanical thrombectomy.

Methods: Patients with acute ischemic stroke with unilateral middle cerebral artery M1 segment occlusion eligible for mechanical thrombectomy will be enrolled. We adopt a 3 + 3 dose-escalation design with a duration escalation schedule of 0, 1, 2, 3, 4, and 5 min × 4 cycles for the ischemic post-conditioning study. After successful reperfusion following mechanical thrombectomy, the balloon for ischemic post-conditioning will be inflated at the site proximal to the culprit lesion four times for 0-5 min with low-pressure (3-4 atmospheres) inflations, each separated by 0-5 min of reflow. We pre-defined the major responses (vessel perforation or rupture, reocclusion of the culprit vessel after ischemic post-conditioning, vessel dissection, severe vasospasm, ischemic post-conditioning related thrombotic events, and rupture of the balloon used for ischemic post-conditioning) as the stopping rules. Each patient will undergo a rigorous evaluation to determine the safety, tolerability, and maximum tolerable duration of ischemic post-conditioning.

Discussion: This will be the first clinical study to ascertain the safety and tolerability of ischemic post-conditioning in patients with acute ischemic stroke receiving mechanical thrombectomy. The maximum tolerable duration obtained in this study will also serve as a starting point for future studies on the efficacy of ischemic post-conditioning.

Clinical trial registration: [https://ichgcp.net/clinical-trials-registry/NCT05153655" title="See in ClinicalTrials.gov">NCT05153655].

Keywords: acute ischemic stroke; dose-escalation; ischemia-reperfusion injury; ischemic post-conditioning; mechanical thrombectomy.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Wu, Zhang, Zhao, Ji and Wei.

Figures

FIGURE 1

The 3 + 3 dose-escalation trial design. The study starts with three patients. (a) If no major response occurs in any of the three patients, the next duration will be used. (b) If a major response occurs in one patient, then three more patients will be enrolled to further assess the safety and tolerability of the same duration; if no additional major response occurs, the duration will be escalated to the next dose; if an additional major response occurs, the study will be stopped, and the previous dose will be defined as the maximum tolerable duration of ischemic post-conditioning. (c) If a major response happens in 2–3 patients, the study will be stopped, and the previous dose will be defined as the maximum tolerable duration. The incremental schedule of the duration is 0, 1, 2, 3, 4, and 5 min × 4 cycles.