CardioPulmonary Resuscitation With Argon (CPAr) Trial (CPAr)

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiac Arrest With Successful Resuscitation; Cardiac Arrest, Out-Of-Hospital
• Intervention / Treatment: Drug: Noble gas Argon

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Giulia Merigo, MSc; Phone Number: +39 0250320463; Email: giulia.merigo@unimi.it
• Study Contact Backup: Name: Antonella Vasamì; Phone Number: 4450 +39 02390141; Email: antonella.vasami@marionegri.it

Study Locations

• Italy
  • GE
    • Genova, GE, Italy, 16132
      • Recruiting
      • Ospedale Policlinico San Martino di Genova
      • Contact: Chiara Robba, MD,PhD; Phone Number: +39 0105551; Email: chiara.robba@unige.it
  • MB
    • Monza, MB, Italy, 20900
      • Recruiting
      • Ospedale San Gerado
      • Contact: Giuseppe Foti, MD; Email: g.foti@asst-monza.it
  • Milan
    • Milan, Milan, Italy, 20122
      • Recruiting
      • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
      • Contact: Giuseppe Ristagno, MD,PhD; Email: giuseppe.ristagno@unimi.it
  • Parma
    • Parma, Parma, Italy, 43126
      • Not yet recruiting
      • Azienda Ospedaliero - Universitaria Di Parma
      • Contact: Edoardo Picetti, MD; Phone Number: +39 0521703175; Email: epicetti@ao.pr.it
  • Pordenone
    • Pordenone, Pordenone, Italy, 33170
      • Recruiting
      • Ospedale Civile Santa Maria degli Angeli di Pordenone
      • Contact: Tommaso Pellis, MD; Phone Number: +39 0434 399111; Email: tommaso.pellis@asfo.sanita.fvg.it
  • RM
    • Roma, RM, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
      • Contact: Claudio Sandroni, MD; Email: claudio.sandroni@policlinicogemelli.it
  • Reggio Emilia
    • Reggio Emilia, Reggio Emilia, Italy, 42123
      • Not yet recruiting
      • Arcispedale Santa Maria Nuova di Reggio Emilia
      • Contact: Giovanni Salati, MD; Phone Number: +39 0522 296111; Email: giovanni.salati@ausl.re.it
  • TS
    • Trieste, TS, Italy, 34148
      • Recruiting
      • Azienda Sanitaria Universitaria Giuliano Isontina (Asugi) di Trieste
      • Contact: Erik Roman Pognuz, MD,PhD; Phone Number: +39 040 399 5943; Email: erik.romanpognuz@asugi.sanita.fvg.it
  • Trento
    • Trento, Trento, Italy, 38122
      • Recruiting
      • Ospedale Santa Chiara Di Trento
      • Contact: Alberto Cucino, MD; Phone Number: +39 0461 903111; Email: alberto.cucino@apss.tn.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Patients will be ventilated with a mixture of Ar 70%/O2 30% for 4 hours	Drug: Noble gas Argon; Ventilation with Ar 70%/O2 30% in comatose patients resuscitated from OHCA with the use of an experimental mechanical ventilator.
No Intervention: Control-standard; Ventilation with a FiO2 of 30% in room air is continued for 4 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	The incidence, the timing, and the duration of the need to stop Ar 70% treatment in order to maintain the SPO2> 90%. The incidence of potentially Ar-attributable hemodynamic adverse events (i.e. arterial hypotension not responsive to fluids and/or vasoactive/inotropic drugs).	1 month
Brain injury	Ar effect on brain injury is assessed through MRI (imaging) if patient remains comatose	96 hours
Myocardial preservation	Ar effect on myocardial protection is assessed through measure of hs-cTnT release	Up to 96 hours
Survival	Effect of argon on survival after cardiac arrest (days)	ICU discharge (assessed up to 7 days), 1-month, 6 months
Neurological recovery	Neurological functional recovery is assessed with the CPC score	ICU discharge (assessed up to 7 days), 1-month, 6 months
Multiorgan function	Multiorgan function is assessed through the evaluation of sequential organ failure assessment score (SOFA). The score sequentially assesses the presence and severity of dysfunctions in six organ systems: respiratory, cardiovascular, coagulation, hepatic, neurological and renal scoring 0 to 4 points per each one of the following: PaO2-fiO2 ratio; Mean arterial pressure (mmHg) or vasoactive treatment; Creatinine (mg/dL) or 24-h diuresis (ml/24h); Platelet count (x103/mm3); Serum bilirubin (mg/dL); Glasgow coma scale The following markers are also assessed: transaminases (UI/L) Pancreatic amilase, lipase (UI/L)	Up to 96 hours

Collaborators and Investigators

• Sponsor: Mario Negri Institute for Pharmacological Research
• Investigators: Principal Investigator: Giuseppe Ristagno, MD, PhD, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2022
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: July 26, 2022
• First Submitted That Met QC Criteria: July 28, 2022
• First Posted (Actual): August 1, 2022

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 11, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Cardiac arrest; Cardiopulmonary resuscitation; Argon.
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Arrest; Out-of-Hospital Cardiac Arrest
• Other Study ID Numbers: IRFMN-7557

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No