Clinical trial NCT05482945: CardioPulmonary Resuscitation With Argon (CPAr) Trial
Official title: CardioPulmonary Resuscitation With Argon (CPAr) Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cardiac Arrest, Out-Of-Hospital
Cardiac Arrest With Successful Resuscitation
Keywords: Cardiac arrest; Cardiopulmonary resuscitation; Argon.
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
First posted: 2022-08-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The intervention (Ar/O2 or standard ventilation) is assigned to the patient using a centrally generated randomization plan, balanced by centre.
Primary purpose: TREATMENT

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 aim of the CPAr trial is to evaluate feasibility and safety of Ar/O2 ventilation in patients resuscitated from CA. Activity endpoints will be also evaluated to assess effects of Ar.

Detailed description: The trial is a multicenter, randomized, controlled, single blinded, phase I and pre marketing study in patients resuscitated from Out-of-hospital cardiac arrest (OHCA). The adoption of a randomized design in a phase I trial aiming at a safety assessment of a new ventilation mixture in a very critical population is justified and necessary in the absence of reliably comparable populations on which to base estimates of a potential excess of adverse events/side effects.

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). Since a reliable estimate of the incidence and characteristics of the clinical events assumed as endpoints is not available in the literature, a randomized assignment is the only way to ensure 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.

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

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 1 month
Secondary outcomes:
measure: Myocardial preservation
timeFrame: 96 hours
measure: Neuronal preservation
timeFrame: 96 hours
measure: Brain injury
timeFrame: 96 hours
measure: Survival
timeFrame: 6 months
measure: Neurological recovery
timeFrame: 6 months
measure: Multiorgan function
timeFrame: 96 hours
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Azienda Ospedaliera Universitaria delle Marche
state: AN
city: Monza
country: Italy
facility: Ospedale San Gerado
state: Milano
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
state: MI
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
state: RM
Study officials:
affiliation: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Giuseppe Ristagno, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: