Preclinical studies suggest that argon (Ar) might diminish the neurological and myocardial damage after any hypoxic-ischemic insult. Indeed, Ar has been tested in different models of ischemic insult, at concentrations ranging from 20% up to 80%. Overall, Ar emerged as a protective agent on cells, tissues and organs, showing less cell death, reduced infarct size and faster functional recovery. More specifically, encouraging data has been reported in animal studies on cardiac arrest (CA) in which a better and faster neurological recovery was achieved when Ar was used in the post-resuscitation ventilation. More importantly, these benefits have been replicated in different studies, enrolling both small and large animals. Finally, ventilation with Ar in O2 has been demonstrated to be safe both in animals and humans. Based on this evidence, a clinical translation is advocated. Thus, the CardioPulmonary resuscitation with Argon - CPAr trial has been conceived. The trial initially started as phase I-II trial to specifically address the question about the safety of the post resuscitation Ar-treatment. The available data on the first 30 randomized patients, evaluated by the Data Safety Monitoring Board (DSMB), were considered absolutely reassuring with regard to the safety of the experimental treatment. In this perspective, the DSMB supported the continuation of the study as a phase II trial, maintaining the study protocol in all its aspects. Thus, the aim of the CPAr trial is now to evaluate efficacy in reducing post-CA neurological injury of Ar/O2 ventilation in patients resuscitated from CA.

The trial is a multicenter, randomized, controlled, single blinded, phase II and pre marketing study in patients resuscitated from Out-of-hospital cardiac arrest (OHCA).

All eligible patients will be treated in full and documented compliance with the European ResuscitationCouncil (ERC)/European Society of Intensive Care Medicine (international guidelines and local post resuscitation protocols). In addition, a randomized assignment ensures a strict comparability for both the periods of data collection of safety end-points (to be assessed blindly by the events Committee): the four hours of duration of study treatment, and the longer period of possibly related clinical events during 6 months follow up.

Inclusion Criteria:

• ICU admission after resuscitation from witnessed non-traumatic out-of-hospital cardiac arrest (OHCA) of presumably cardiac etiology with a presenting shockable rhythm;
• age ≥ 18 years;
• unconsciousness after return of spontaneous circulation (ROSC);
• duration of CPR ≤ 40 mins;
• initiation of study intervention ≤ 4 hrs from ROSC;
• stable SaO2 ≥ 94% with a FiO2 of 30%.

Exclusion Criteria:

• Non-witnessed CA;
• CA of traumatic origin or from a non-presumably cardiac cause;
• CA with a non-shockable presenting rhythm (pulseless electrical activity and asystole);
• female of childbearing potential defined as younger of 50 years;
• pregnancy;
• known terminal illness;
• pre-CA cerebral performance category (CPC) ≥ 3;
• initiation of the study intervention > 4 hrs from ROSC;
• participation to another clinical trial