Cardiac Arrest, Out-Of-HospitalPhase 2CPArNCT05482945
CardioPulmonary Resuscitation With Argon (CPAr) Trial
A Phase 2 study testing Noble gas Argon in people with Cardiac Arrest, Out-Of-Hospital and Cardiac Arrest With Successful Resuscitation, run by Mario Negri Institute for Pharmacological Research at 9 sites in Italy.
Trial 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%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Arrest, Out-Of-Hospital, Cardiac Arrest With Successful Resuscitation
- What is being tested?
- Noble gas Argon
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 9 sitesItaly
- Study dates
- 30 May 2022to 30 Jun 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%.
Who cannot join
- 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;
Show all 9Show fewer
- pre-CA cerebral performance category (CPC) ≥ 3;
- initiation of the study intervention > 4 hrs from ROSC;
- participation to another clinical trial
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
Italy9 sites, 9 recruiting
- Recruiting
Ospedale Policlinico San Martino di Genova
Genova, GE, 16132
Chiara Robba, MD,PhD, +39 0105551, chiara.robba@unige.it
- Recruiting
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, Milan, 20122
Giuseppe Ristagno, MD,PhD, giuseppe.ristagno@unimi.it
- Recruiting
Ospedale San Gerado
Monza, MB, 20900
Giuseppe Foti, MD, g.foti@asst-monza.it
- Not yet recruiting
Azienda Ospedaliero - Universitaria di Parma
Parma, Parma, 43126
Edoardo Picetti, MD, +39 0521703175, epicetti@ao.pr.it
- Recruiting
Ospedale Civile Santa Maria degli Angeli di Pordenone
Pordenone, Pordenone, 33170
Tommaso Pellis, MD, +39 0434 399111, tommaso.pellis@asfo.sanita.fvg.it
- Not yet recruiting
Arcispedale Santa Maria Nuova di Reggio Emilia
Reggio Emilia, Reggio Emilia, 42123
Giovanni Salati, MD, +39 0522 296111, giovanni.salati@ausl.re.it
- Recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, RM, 00168
Claudio Sandroni, MD, claudio.sandroni@policlinicogemelli.it
- Recruiting
Ospedale Santa Chiara di Trento
Trento, Trento, 38122
Alberto Cucino, MD, +39 0461 903111, alberto.cucino@apss.tn.it
- Recruiting
Azienda Sanitaria Universitaria Giuliano Isontina (Asugi) di Trieste
Trieste, TS, 34148
Erik Roman Pognuz, MD,PhD, +39 040 399 5943, erik.romanpognuz@asugi.sanita.fvg.it
About this study
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.
Read the 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.
- Being tested
- Noble gas Argon
- Keywords
- Cardiac arrest; Cardiopulmonary resuscitation; Argon.
- Medical subject headings
- Out-of-Hospital Cardiac Arrest, Heart Arrest
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Noble gas ArgonDrug
Ventilation with Ar 70%/O2 30% in comatose patients resuscitated from OHCA with the use of an experimental mechanical ventilator.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Patients will be ventilated with a mixture of Ar 70%/O2 30% for 4 hours Receives: Drug: Noble gas Argon |
| Control-standard | No intervention | Ventilation with a FiO2 of 30% in room air is continued for 4 hours. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 48 hours
Secondary outcomes (6)
Myocardial preservation
Ar effect on myocardial protection is assessed through measure of hs-cTnT release
Measured: Up to 96 hours
Brain injury
Ar effect on brain injury is assessed through MRI (imaging) if patient remains comatose
Measured: 96 hours
Survival
Effect of argon on survival after cardiac arrest (days)
Measured: ICU discharge (assessed up to 7 days), 1-month, 6 months
Neurological recovery
Neurological functional recovery is assessed with the CPC score
Measured: 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)
Measured: Up to 96 hours
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).
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2022
- Study start30 May 2022
- Primary completion31 Mar 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiac Arrest, Out-Of-HospitalStudies of the same condition, open and under way.
- More trials run by Mario Negri Institute for Pharmacological ResearchThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The intervention (Ar/O2 or standard ventilation) is assigned to the patient using a centrally generated randomization plan, balanced by centre.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giuseppe Ristagno, MD, PhD, Principal investigator, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05482945
- Sponsor's protocol ID
- IRFMN-7557
- Acronym
- CPAr
- Status last verified
- Sep 2025
- First submitted
- 26 Jul 2022
- Last updated
- 17 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41079544
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CardioPulmonary Resuscitation With Argon (CPAr) Trial
- ClinicalTrials.gov ID
- NCT05482945
- Acronym / sponsor ID
- CPAr / IRFMN-7557
- Keywords
- Cardiac arrest; Cardiopulmonary resuscitation; Argon.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- 30 May 2022 (actual)
- Primary completion
- 31 Mar 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 1 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- The intervention (Ar/O2 or standard ventilation) is assigned to the patient using a centrally generated randomization plan, balanced by centre.
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: Noble gas ArgonPatients will be ventilated with a mixture of Ar 70%/O2 30% for 4 hours |
| Control-standard | No intervention | –Ventilation with a FiO2 of 30% in room air is continued for 4 hours. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (9 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Noble gas ArgonVentilation with Ar 70%/O2 30% in comatose patients resuscitated from OHCA with the use of an experimental mechanical ventilator. | Drug | Intervention |
Primary outcome
Neuronal preservation
Time frame: 48 hours
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.
6 secondary outcomes
Myocardial preservation
Time frame: Up to 96 hours
Brain injury
Time frame: 96 hours
Survival
Time frame: ICU discharge (assessed up to 7 days), 1-month, 6 months
Neurological recovery
Time frame: ICU discharge (assessed up to 7 days), 1-month, 6 months
Multiorgan function
Time frame: Up to 96 hours
Incidence of Treatment-Emergent Adverse Events
Time frame: 1 month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2025.
- Derived from this study: PubMed 41079544Ristagno 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.
- Individual participant dataSharing planned: No
Related trials for Cardiac Arrest, Out-Of-Hospital
Not yet recruitingObservational study
CAROTID DOPPLER AND CEREBRAL OXIMERY IN POST CARDIAC ARREST ICU PATIENTS
Cardiac Arrest (CA), Carotid Doppler
Active, not recruitingPhase 3
The Danish Out-of-Hospital Cardiac Arrest Study
Out-Of-Hospital Cardiac Arrest, Post-Cardiac Arrest Syndrome
Not yet recruiting
Compression-Only Versus Standard Basic Life Support Training in Nursing Students
Cardiopulmonary Resuscitation, Out-of-Hospital Cardiac Arrest
Not yet recruiting
Execution of Prehospital Transesophageal Echocardiography During Cardiopulmonary Resuscitation in Patients With Out-of-hospital Cardiac Arrest
Out-of-hospital Cardiac Arrest (OHCA)
Active, not recruiting
The REVIVE-PEEP Trial: Positive End-expiratory Pressure Versus Sham Valve/Zero End-expiratory Pressure in Cardiopulmonary Resuscitation During Manual Ventilation to Improve Neurological Outcomes at Discharge in Adult Patients Suffering an Out-of-hospital Cardiac Arrest
Cardiac Arrest, Out-Of-Hospital
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Giuseppe Ristagno, MD, PhD principal investigator
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Noble gas Argon in people with Cardiac Arrest, Out-Of-Hospital and Cardiac Arrest With Successful Resuscitation, run by Mario Negri Institute for Pharmacological Research at 9 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giulia Merigo, MSc (+39 0250320463, giulia.merigo@unimi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neuronal preservation (time frame: 48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05482945, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2025.