CardioPulmonary resuscitation with Argon (CPAr) trial

2024-516864-27-00 Protocol IRFMN 7557/8154 Therapeutic exploratory (Phase II) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 11 sites · Protocol IRFMN 7557/8154

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Authorised, recruitment pending
Participants planned 120
Countries 1
Sites 11

Cardiac arrest

The objective of the CPAr trial is to evaluate the efficacy in reducing post-CA neurological injury of Ar 70%/O2 30% ventilation in patients resuscitated from OHCA with an experimental ventilator, specifically modified to permit Ar/O2 ventilation.

Key facts

Sponsor
Istituto Di Ricerche Farmacologiche Mario Negri
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Decision date (initial)
2024-10-07
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Società Italiana Acetilene e derivati - S.I.A.D. Spa · Ministry of Health, Italy, RF-2019-12371416

External identifiers

EU CT number
2024-516864-27-00
EudraCT number
2018-003047-32
ClinicalTrials.gov
NCT05482945

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The objective of the CPAr trial is to evaluate the efficacy in reducing post-CA neurological injury of Ar 70%/O2 30% ventilation in patients resuscitated from OHCA with an experimental ventilator, specifically modified to permit Ar/O2 ventilation.

Secondary objectives 4

  1. Hs-cTnT plasma concentration for evaluation of Ar activity on myocardial preservation
  2. Brain imaging (MRI with DWI and DTI, in patients that remain comatose), for evaluation of Ar activity on neuronal preservation;
  3. Multiorgan function (circulating biomarkers)
  4. Survival and CPC score up to 6 months, for evaluation of functional outcome.

Conditions and MedDRA coding

Cardiac arrest

VersionLevelCodeTermSystem organ class
20.0 LLT 10003109 Arrest cardiac 10007541

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 CardioPulmonary resuscitation with Argon (CPAr) trial
Prospective, interventional, multicenter, randomized, phase II to assess efficacy of ventilation with an argon/oxygen mixture provided by an experimental device in patients resuscitated from out-of-hospital cardiac arrest
 Randomised Controlled None Argon: Patients who reach an adequate arterial O2 saturation (SaO2) (i.e. 94-98%) will be randomly assigned either to: a) the experimental arm, in which patients are ventilated with a mixture of Ar 70%/O2 30% for 4 hours; or b) the control-standard arm, in which the ventilation with a FiO2 of 30% in room air is continued for 4 hours. For the Ar-treatment group the patients are ventilated with a gas-mix of Ar 70% and O2 30% administered by a dedicated ventilator, verified and tested for clinical use and compatible with Ar ventilation as certified by the manufacturer. The Ar/O2 blend is supplied to the ventilator from dedicated gas tanks containing the specific gas mixture certified by SIAD spa (certified UNI EN ISO 9001:2015). In the instance of stable desaturation in the experimental group, Ar administration will be discontinued to increase the FiO2 in order to re-establish and maintain the standard O2 saturation. It will be possible to test the compatibility of Ar/O2 ventilation with a satisfactory O2 saturation over the whole 4-hour observational period.
control-standard: Patients randomly assigned to the control arm will receive standard post-resuscitation treatment and ventilation with the use of a standard ICU ventilator provided with Air/O2. SaO2, SpO2, and O2 requirements will be monitored in order to have comparative data to assess safety profile of Ar/O2 ventilation.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. witnessed non-traumatic OHCA of presumably cardiac etiology with a presenting shockable rhythm
  2. age ≥ 18 years
  3. unconsciousness after return of spontaneous circulation (ROSC)
  4. duration of CPR ≤ 40 mins
  5. Initiation of study intervention ≤ 4 hrs from ROSC
  6. stable SaO2 ≥ 94% (according to the physician’s criteria), with a FiO2 of 30%

Exclusion criteria 11

  1. age < 18 years
  2. non-witnessed CA
  3. CA of traumatic origin
  4. non-presumably cardiac cause
  5. non-shockable presenting rhythm (pulseless electrical activity and asystole)
  6. women of childbearing potential defined as younger of 50 years
  7. pregnancy
  8. known terminal illness
  9. pre-CA cerebral performance category (CPC) ≥ 3
  10. initiation of the study intervention > 4 hrs from ROSC
  11. participation to another clinical trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. 48 h Serum Neuron Specific Enolase (NSE) concentration for evaluation of Ar activity on neuronal preservation.

Secondary endpoints 4

  1. hs-cTnT plasma concentration for evaluation of Ar activity on myocardial preservation;
  2. Brain imaging (MRI with DWI and DTI, in patients that remain comatose), for evaluation of Ar activity on neuronal preservation;
  3. Multiorgan function (circulating biomarkers);
  4. Survival and CPC score up to 6 months, for evaluation of functional outcome.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Argon/Oxygen mixture

PRD11492592 · Product

Active substance
Argon
Other product name
Ar/O2
Pharmaceutical form
INHALATION GAS
Route of administration
INHALATION GAS
Max daily dose
70 % percent
Max total dose
70 % percent
Max treatment duration
1 Day(s)
Authorisation status
Not Authorised
MA holder
ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI IRCCS
Paediatric formulation
No
Orphan designation
No

Comparator 1

Nitrous Oxide

SCP102635536 · ATC

Active substance
Nitrous Oxide
Substance synonyms
NITROGEN DIOXIDE, DINITROGENII OXIDUM, NITROGEN MONOXIDE, LAUGHING GAS
Route of administration
INHALATION GAS
Max daily dose
30 % percent
Max total dose
30 % percent
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V03AN01 — OXYGEN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Di Ricerche Farmacologiche Mario Negri

7 Total trials 3 Recruiting 2 Ended
Academic / Non-commercial
Sponsor organisation
Istituto Di Ricerche Farmacologiche Mario Negri
Address
Via Mario Negri 2
City
Milan
Postcode
20156
Country
Italy

Scientific contact point

Organisation
Istituto Di Ricerche Farmacologiche Mario Negri
Contact name
Roberto Latini

Public contact point

Organisation
Istituto Di Ricerche Farmacologiche Mario Negri
Contact name
Roberto Latini

Third parties 1

OrganisationCity, countryDuties
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
ORG-100006307
 Milan, Italy Code 2

Locations

1 EU/EEA country · 11 investigational sites

By country

CountryMS statusPlanned subjectsSites
Italy Authorised, recruitment pending 120 11
Rest of world — 0 —

Investigational sites

Italy

11 sites · Authorised, recruitment pending
Azienda Ospedaliera Friuli Occidentale, ASFO Pordenone
SC Anestesia e Rianimazione, via Montereale 24, 33170, Pordenone
Azienda Ospedaliero Universitaria Delle Marche
SOD Clinica di Anestesia e Rianimazione Generale, Respiratoria e del Trauma Maggiore, Via Conca 71, 60126, Ancona
Arcispedale S. Maria Nuova in Reggio Emilia
Rianimazione, Viale Risorgimento 80, 42123, Reggio Emilia
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
UOC Anestesia e Terapia Intensiva Adulti, Via Francesco Sforza 35, 20122, Milan
Azienda Sanitaria Universitaria Giuliano Isontina
Anestesia e Rianimazione, Via Costantino Costantinides 2, 34128, Trieste
Ospedale Santa Chiara
Rianimazione Generale, Anestesia e Rianimazione 1,, Largo Medaglie d'oro, 9
IRCSS Ospedale Policlinico San Martino
Anestesia e Rianimazione, Largo Rosanna Benzi 10, 16132, Genova
Azienda Ospedaliero - Universitaria di Parma
Struttura Complessa Terapia Intensiva Anestesia e Rianimazione, viale Antonio Gramsci 14, 43126, Parma
Ospedale Maggiore Carlo Alberto Pizzardi – AUSL Bologna, Bologna (IT)
UOC Rianimazione ed Emergenza Territoriale 118 –, L.go Bartolo Nigrisoli, 2,, Bologna
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Dipartimento di Scienze dell'Emergenza, Anestesiologiche e della Rianimazione, Largo Francesco Vito 1, 00168, Rome
Fondazione IRCCS San Gerardo Dei Tintori
Emergenza Urgenza - Anestesia e Rianimazione, Via Giovanni Battista Pergolesi 33, 20900, Monza

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_ Protocol _2018-003047-32 for publication 3.0
Protocol (for publication) D2_ Protocol modification nr1 _2024-516864-27-00_clean 4.0
Protocol (for publication) D2_ Protocol modification nr1_CT 2024-516864-27-00_trackchanges 4.0
Recruitment arrangements (for publication) Blank document 1
Recruitment arrangements (for publication) K1_ Recruitment arrangements 1
Recruitment arrangements (for publication) K1_ Recruitment arrangements PDF 1
Subject information and informed consent form (for publication) L1_ SIS and ICF Adults 2.0
Subject information and informed consent form (for publication) L1_ SIS and ICF GENERAL _CPAR 4.0
Subject information and informed consent form (for publication) L1_ SIS and ICF GENERAL _CPAR _clean 4.1
Subject information and informed consent form (for publication) L1_ SIS and ICF GENERAL _CPAR _CLEAN_ 4.2
Subject information and informed consent form (for publication) L1_ SIS and ICF GENERAL _CPAR _TRACKCHANGE 4.1
Subject information and informed consent form (for publication) L1_ SIS and ICF GENERAL _CPAR _TRACKCHANGE_ 4.2
Subject information and informed consent form (for publication) L1_ SIS and ICF_Adult_trackchanges 3.0
Subject information and informed consent form (for publication) L1_ SIS and ICF_Adult_version clean 3.0
Subject information and informed consent form (for publication) L2_ Other subject information material _Privacy 1
Subject information and informed consent form (for publication) L2_ Other subject information material -Informativa e Consenso dati _CPAr 1
Subject information and informed consent form (for publication) L2_ Other subject information material- MMG 3.0
Subject information and informed consent form (for publication) L2_ Other subject information material- MMG_versione clean 3.0
Summary of Product Characteristics (SmPC) (for publication) Argon 1
Summary of Product Characteristics (SmPC) (for publication) G2_ SmPC_Oxygen 1
Synopsis of the protocol (for publication) D1_ Protocol synopsis_2018-003047-32 for publication 3.0
Synopsis of the protocol (for publication) D1_ Protocol synopsis_2024-516864-27-00 4.0
Synopsis of the protocol (for publication) D1_ Protocol synopsis_2024-516864-27-00_trackchanges 4.0

Application history

4 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-09-10 Italy Acceptable
2024-10-02
 2024-10-07
2 SUBSTANTIAL MODIFICATION SM-1 2024-11-14 Italy Acceptable
2025-01-24
 2025-03-05
3 NON SUBSTANTIAL MODIFICATION NSM-1 2025-03-11 Italy Acceptable
2025-01-24
 2025-03-11
4 SUBSTANTIAL MODIFICATION SM-2 2025-12-11 Italy Acceptable 2026-03-16

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