CardioPulmonary resuscitation with Ar gon (CP Ar): A protocol for a randomised controlled multicentre clinical trial

Abstract

Aims: 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).

Methods: 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.

Conclusion: 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.

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

Keywords: Argon; Cardiac arrest; Clinical trial protocol; Inhaled gases; Neuroprotection.

Fig. 1

Inclusion and randomization flow diagram. CA, cardiac arrest; CPC, cerebral performance category score; CPR, cardiopulmonary resuscitation; EtCO₂, end-tidal carbon dioxide; FiO₂, inspiratory oxygen fraction; MAP, mean arterial pressure; PaCO₂, arterial partial pressure of carbon dioxide; OHCA, out-of-hospital cardiac arrest; ROSC, return of spontaneous circulation; SaO₂, arterial oxygen saturation.

Fig. 2

Study flow diagram. ABG, arterial blood gas; CA, cardiac arrest; hs-cTnT, high sensitivity cardiac troponin T; ICU, intensive care unit; NSE, neuron-specific enolase.