Neuroprotective effect of early remote ischaemic post-conditioning after out-of-hospital cardiac arrest (RIPOST-CA): study protocol for a randomised, single-blinded, monocentric, controlled trial.

Introduction: Hypoxic-ischaemic brain injury is the leading cause of death and long-term disability after out-of-hospital cardiac arrest and is driven by the ischaemia-reperfusion syndrome, for which no specific treatment exists. Remote ischaemic post-conditioning (brief, repeated cycles of limb ischaemia and reperfusion delivered with a pneumatic cuff), is protective across ischemia-reperfusion conditions. We aim to assess whether early conditioning reduces hypoxic-ischaemic brain injury after out-of-hospital cardiac arrest. Methods: This single-centre, single-blinded, randomised (1:1) controlled trial with blinded assessment of the outcome, enrols 48 comatose adults resuscitated from out-of-hospital cardiac arrest. Participants receive standard post-resuscitation care with three sham cuff sessions, or standard care plus three sessions of conditioning (thigh cuff, four cycles of 5-min inflation at 200 mmHg alternating with 5-min deflation), the first within 4 h of return of spontaneous circulation and repeated at the 12th and 24th hour. Randomisation is stratified by initial rhythm (shockable versus non-shockable). The primary endpoint is the change in serum neurofilament light chain between the 6th and 72nd hour after return of spontaneous circulation. Secondary endpoints include daily Sequential Organ Failure Assessment scores (days 1-3), serum neuron-specific enolase and protein S100-B kinetics, in-intensive care unit mortality by cause, and a favourable neurological outcome (modified Rankin Scale 0-3) at intensive care unit discharge and at 90 days. Conclusion: RIPOST-CA is the first randomised trial to evaluate early remote ischemic post-conditioning on brain-injury biomarkers after out-of-hospital cardiac arrest. Its results could inform larger clinical trials of this simple, non-invasive intervention.