CardioPulmonary Resuscitation With Argon (CPAr) Trial

NCT05482945 | Recruiting Phase 2 DMC

• 1 other identifier: IRFMN-7557
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 9

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.

Conditions

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

Keywords

Cardiac arrest; Cardiopulmonary resuscitation; Argon.

Outcome Measures

Primary Outcomes (1)

• Neuronal preservation

  Efficacy of Argon treatment in reducing post-CA neurological injury, assessed as 48hr serum concentration of the Neuron Specific Enolase (NSE), an established biomarker of brain injury.

  48 hours

Secondary Outcomes (6)

• Myocardial preservation

  Up to 96 hours

• Brain injury

  96 hours

• Survival

  ICU discharge (assessed up to 7 days), 1-month, 6 months

• Neurological recovery

  ICU discharge (assessed up to 7 days), 1-month, 6 months

• Multiorgan function

  Up to 96 hours

Study Arms (2)

Intervention

EXPERIMENTAL

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

Drug: Noble gas Argon

Control-standard

NO INTERVENTION

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

Interventions

Noble gas Argon DRUG

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

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (9)

Ospedale Policlinico San Martino di Genova

Genova, GE, 16132, Italy

RECRUITING

Ospedale San Gerado

Monza, MB, 20900, Italy

RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Milan, 20122, Italy

RECRUITING

Azienda Ospedaliero - Universitaria di Parma

Parma, Parma, 43126, Italy

NOT YET RECRUITING

Ospedale Civile Santa Maria degli Angeli di Pordenone

Pordenone, Pordenone, 33170, Italy

RECRUITING

Arcispedale Santa Maria Nuova di Reggio Emilia

Reggio Emilia, Reggio Emilia, 42123, Italy

NOT YET RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, RM, 00168, Italy

RECRUITING

Ospedale Santa Chiara di Trento

Trento, Trento, 38122, Italy

RECRUITING

Azienda Sanitaria Universitaria Giuliano Isontina (Asugi) di Trieste

Trieste, TS, 34148, Italy

RECRUITING

Related Publications (1)

• 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.

  PMID: 41079544 DERIVED

MeSH Terms

Conditions

Out-of-Hospital Cardiac Arrest; Heart Arrest

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Giuseppe Ristagno, MD, PhD

  Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giulia Merigo, MSc

CONTACT

+39 0250320463; giulia.merigo@unimi.it

Antonella Vasamì

CONTACT

+39 02390141; antonella.vasami@marionegri.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The intervention (Ar/O2 or standard ventilation) is assigned to the patient using a centrally generated randomization plan, balanced by centre.

Study Record Dates

• First Submitted: July 26, 2022
• First Posted: August 1, 2022
• Study Start: May 30, 2022
• Primary Completion: March 31, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (9)