CardioPulmonary resuscitation with Argon (CPAr): A protocol for a randomised controlled multicentre clinical trial

The CardioPulmonary resuscitation with Argon (CPAr) trial evaluates the clinical neuroprotective efficacy and safety of post-resuscitation ventilation with a 70/30 argon/oxygen (Ar/O₂) gas mixture compared to standard care ventilation with 30% O₂ in unconscious adults resuscitated from out-of-hospital cardiac arrest (OHCA).

CPAr is an allocation-concealed, single-blinded, multi-centre, phase II, pre-marketing, randomised controlled trial (RCT). The study aims to recruit 120 patients across tertiary intensive care units (ICUs) in Italy. Eligible participants are unconscious adult OHCA survivors with a shockable presenting rhythm. Upon ICU admission, patients are individually randomised in a 1:1 ratio to receive either 4-h ventilation with 70/30 Ar/O₂ via an experimental ventilator, or standard ICU ventilation with 30% O₂. All patients receive guideline-based post-resuscitation care. Inclusion is conducted under a deferred consent model, with consent obtained from patients or legal representatives once clinically appropriate.The primary clinical efficacy outcome is serum neuron-specific enolase (NSE) concentration at 48 h, as a surrogate marker of neurological injury. Secondary outcomes include markers of myocardial and multiorgan injury, neuroimaging signs of brain injury, survival, and neurological recovery (Cerebral Performance Category, CPC) up to 6 months. Safety outcomes include the incidence, timing, and duration of O₂ desaturation requiring discontinuation of Ar, and haemodynamic adverse events. Patients are followed up to 6 months, with outcome assessment at ICU/hospital discharge, 1- and 6-months post-CA. A centralized plasma and serum biobank will support future mechanistic analyses.

CPAr trial is the first RCT to assess the efficacy and safety of Ar ventilation in humans following OHCA and may inform future neuroprotective strategies in post-resuscitation care.

EudraCT-No.: 2018-003047-32; CTIS code: 2024-516864-27-00; ClinicalTrials.gov identifier: NCT05482945.