CardioPulmonary Resuscitation With Argon (CPAr) Trial

NCT ID: NCT05482945

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-30
• Study Completion Date: 2026-06-30

Brief Summary

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.

Detailed Description

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.

Conditions

Cardiac Arrest, Out-Of-Hospital; Cardiac Arrest With Successful Resuscitation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Intervention

Patients will be ventilated with a mixture of Ar 70%/O2 30% for 4 hours

Group Type: EXPERIMENTAL

Noble gas Argon

Intervention Type: DRUG

Ventilation with Ar 70%/O2 30% in comatose patients resuscitated from OHCA with the use of an experimental mechanical ventilator.

Control-standard

Ventilation with a FiO2 of 30% in room air is continued for 4 hours.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Noble gas Argon

Ventilation with Ar 70%/O2 30% in comatose patients resuscitated from OHCA with the use of an experimental mechanical ventilator.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Giuseppe Ristagno, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Locations

Ospedale Policlinico San Martino di Genova

Genova, GE, Italy

Site Status: RECRUITING

Ospedale San Gerado

Monza, MB, Italy

Site Status: RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Milan, Italy

Site Status: RECRUITING

Azienda Ospedaliero - Universitaria di Parma

Parma, Parma, Italy

Site Status: NOT_YET_RECRUITING

Ospedale Civile Santa Maria degli Angeli di Pordenone

Pordenone, Pordenone, Italy

Site Status: RECRUITING

Arcispedale Santa Maria Nuova di Reggio Emilia

Reggio Emilia, Reggio Emilia, Italy

Site Status: NOT_YET_RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, RM, Italy

Site Status: RECRUITING

Ospedale Santa Chiara di Trento

Trento, Trento, Italy

Site Status: RECRUITING

Azienda Sanitaria Universitaria Giuliano Isontina (Asugi) di Trieste

Trieste, TS, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Giulia Merigo, MSc

Role: CONTACT

giulia.merigo@unimi.it

+39 0250320463

Antonella Vasamì

Role: CONTACT

antonella.vasami@marionegri.it

+39 02390141 ext. 4450

Facility Contacts

Chiara Robba, MD,PhD

Role: primary

chiara.robba@unige.it

+39 0105551

Giuseppe Foti, MD

Role: primary

g.foti@asst-monza.it

Giuseppe Ristagno, MD,PhD

Role: primary

giuseppe.ristagno@unimi.it

Edoardo Picetti, MD

Role: primary

epicetti@ao.pr.it

+39 0521703175

Tommaso Pellis, MD

Role: primary

tommaso.pellis@asfo.sanita.fvg.it

+39 0434 399111

Giovanni Salati, MD

Role: primary

giovanni.salati@ausl.re.it

+39 0522 296111

Claudio Sandroni, MD

Role: primary

claudio.sandroni@policlinicogemelli.it

Alberto Cucino, MD

Role: primary

alberto.cucino@apss.tn.it

+39 0461 903111

Erik Roman Pognuz, MD,PhD

Role: primary

erik.romanpognuz@asugi.sanita.fvg.it

+39 040 399 5943

References

Ristagno G, Staszewsky L, Merigo G, Magliocca A, Cucino A, Meessen J, Fumagalli F, Pozzi M, Galazzi A, Sandroni C, Meneguzzi M, Marangone A, Robba C, Roman-Pognuz E, Salati G, Picetti E, Novelli D, Bellani G, Panigada M, Wik L, Garattini S, Foti G, Antonelli M, Zanier E, Grasselli G, Latini R; CPAr Study group. CardioPulmonary resuscitation with Argon (CPAr): A protocol for a randomised controlled multicentre clinical trial. Resusc Plus. 2025 Sep 10;26:101096. doi: 10.1016/j.resplu.2025.101096. eCollection 2025 Nov.

Reference Type: DERIVED

PMID: 41079544 (View on PubMed)

Other Identifiers

IRFMN-7557

Identifier Type: -

Identifier Source: org_study_id