CardioPulmonary Resuscitation With Argon (CPAr) Trial

Cardiac Arrest, Out-Of-Hospital Clinical Trial

— CPAr  

Official title:

CardioPulmonary Resuscitation With Argon (CPAr) Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05482945
• Other study ID #: IRFMN-7557
• Status: Recruiting
• Phase: N/A
• Start date: May 30, 2022
• Est. completion date: September 16, 2025

Study information

• Verified date: June 2023
• Source: Mario Negri Institute for Pharmacological Research
• Contact: Lidia Staszewsky, MD
• Phone: 02390141
• Email: lidia.staszewsky[@]marionegri.it
• Is FDA regulated: No
• Study type: Interventional

Clinical 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%. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 16, 2025
• Est. primary completion date: March 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Arrest With Successful Resuscitation
• Cardiac Arrest, Out-Of-Hospital
• Heart Arrest
• Out-of-Hospital Cardiac Arrest

Intervention

Other:
• Noble gas Argon
Ventilation with Ar 70%/O2 30% in comatose patients resuscitated from OHCA with the use of an experimental mechanical ventilator.

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Universitaria delle Marche	Ancona	AN
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano	MI
Italy	Ospedale San Gerado	Monza	Milano
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma	RM

Sponsors (1)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Myocardial preservation	Ar effect on myocardial protection is assessed through measure of hs-cTnT release	96 hours
Secondary	Neuronal preservation	Ar effect on neuronal preservation is assessed through evaluation of NSE preservation and ultimately on survival (CPC score) will be evaluated.	96 hours
Secondary	Brain injury	Ar effect on brain injury is assessed through MRI (imaging) if patient remains comatose	96 hours
Secondary	Survival	effect of argon on survival after cardiac arrest (days)	6 months
Secondary	Neurological recovery	Neurological functional recovery is assessed with the CPC score	6 months
Secondary	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)	96 hours