Inhaled Nitric Oxide for Cardiac Arrest in Pediatrics and Adults (iNOCAPA)

NCT05868109 | Unknown Phase 2 DMC

• 1 other identifier: 1822
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

Brief Summary

This study is a multi-center, double blind, randomized controlled trial of inhaled nitric oxide (iNO) in children and adults with cardiac arrest (CA). The purpose of this pilot study is to test the feasibility of rapidly randomizing patients to iNO or sham treatment during cardiopulmonary resuscitation (CPR) or shortly after return of circulation (ROC) and evaluate blood biomarkers associated with iNO compared to sham. Return of circulation may refer to return of spontaneous circulation (ROSC) or ROC through extracorporeal cardiopulmonary resuscitation (E-CPR).

Conditions

Cardiac Arrest

Keywords

Neuroprotection; Nitric Oxide

Outcome Measures

Primary Outcomes (2)

• Drug Procedural Feasibility

  Number of successful initiations of iNO or sham among the 40 patients enrolled in the study. We will monitor and improve our rates of enrolment and study intervention by examining and improving upon factors related to protocol compliance.

  We will monitor screening numbers, rates of enrolment of eligible patients and delivery of study intervention according to CONSORT criteria over the 2 year timeframe of study enrolment.

• Drug Procedural Feasibility

  Number of successful continuations of iNO or sham for 72 hours followed by weaning and stopping the study intervention over the next 12 hours. Using real time monitoring of the study intervention we will optimize compliance to the full duration of the study intervention and improve upon any deviations to the study intervention over the full 72 + 12 hours of the study protocol.

  We will monitor compliance to the study intervention during the 72 hours of drug/sham delivery and 12 hours of weaning and stopping the study intervention on each enrolled patient over the 2 years of study enrolment.

Secondary Outcomes (4)

• Monitor recruitment rate

  For study duration, approximately 2 years.

• Monitor time to randomization of eligible patients

  At study enrollment during the 2 years of study recruitment.

• Monitor masking and unmasking events

  During the 2 year study duration and data analysis.

• Study follow-up rates

  For study follow-up, approximately 2.5 years.

Other Outcomes (6)

• Return of spontaneous circulation (ROSC)

  Duration of study enrollment, approximately 2 years.

• Survival at hospital discharge

  For duration of study follow-up, approximately 2 years and 6 months.

• Cerebral performance category score

  For duration of study follow-up, approximately 2 years and 6 months.

Study Arms (2)

Participants with Sham (no nitric oxide)

SHAM COMPARATOR

The mechanical ventilator circuit of the study participants are attached to the inhaled nitric oxide delivery device but nitric oxide is not delivered.

Drug: Sham

Participants with Nitric Oxide

EXPERIMENTAL

The mechanical ventilator circuit of the study participants are attached to the inhaled nitric oxide delivery device and nitric oxide is delivered.

Drug: inhaled nitric oxide (iNO)

Interventions

inhaled nitric oxide (iNO) DRUG

In patients randomized to the this arm, iNO will be delivered into the ventilator circuit through the endotracheal tube or tracheostomy. The dose will be 80 ppm during chest compressions and reduced to 20 ppm immediately following ROC. If the patient is enrolled following ROC, the dose will be 20 ppm. Dose modifications will occur if there is toxicity or if there is a clinical concern. The iNO or sham will be continued for 72 hours or until extubation.

Also known as: INOMAX

Participants with Nitric Oxide

Sham DRUG

In patients randomized to sham, the iNO delivery device will be connected to the ventilator circuit or manual ventilation bag but flow of iNO will not be turned on. For the purposes of patient safety and to maintain blinding, the respiratory therapists (RTs) will continue checks of gas flow, flow adjustments and change iNO gas tanks at rates like routine clinical procedures on patients treated with iNO or sham.

Also known as: Sham intervention with no flow of inhaled nitric oxide to the patient

Participants with Sham (no nitric oxide)

Eligibility Criteria

• Age: 1 Day - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all the following criteria:
• Aged 1 day\* to 80 years on the day the study intervention is started
• In-hospital or out-of-hospital CA with CPR \> 5 minutes
• It is possible to randomize and start the iNO or sham during CPR or within 5 hours of ROC\*\*
• Mechanically ventilated in a study site ICU
• Note: \*Age 1 day is defined as 24 hours and a minimum corrected gestational age ≥ 38 weeks.
• Note: \*\*ROC refers to either ROSC or ROC via extracorporeal cardiopulmonary resuscitation (E-CPR).

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Unwitnessed cardiac arrest
• Cardiac arrest due to birth asphyxia
• Pre-arrest poor neurologic function\*
• Already receiving iNO at the time of CA
• Any condition or diagnosis, in the opinion of the PI, Co-Investigators, or MRPs, in which iNO would have adverse effects on physiology or where the cardiac anatomy and physiology has not yet been adequately assessed
• Any condition or diagnosis, in the opinion of the PI, Co-Investigators, or MRPs, in which iNO would be indicated as therapy post-arrest
• CPR duration \> 45 minutes; if less than 18 years old, in-hospital CPR duration \> 60 minutes\*\*
• Known pregnancy\*\*\*
• Terminal illness ʈ
• Note: \* Poor neurologic function is defined as CPC ≥ 4 or PCPC ≥ 4.
• Note: \*\*CPR duration is defined as total cumulative duration of CPR (i.e., if a patient has multiple arrests with CPR, the duration of these will be added); patients who undergo E-CPR will not be excluded, to maximize recruitment for this feasibility trial.
• Note: \*\*\*B-HCG screening is not required for enrollment in women of reproductive age, but testing will occur as soon as possible (within 6 hours of enrollment).
• Patients who are cannulated to ECMO for cardiorespiratory support will NOT be excluded a priori.
• ʈ The MRP knew that the patient was dying pre-arrest

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Heart and Stroke Foundation of Canada: collaborator

Study Sites (4)

St. Michael's Hospital

Toronto, Ontario, M5B1W8, Canada

NOT YET RECRUITING

Toronto General Hospital

Toronto, Ontario, M5G2C4, Canada

RECRUITING

Toronto Western Hospital

Toronto, Ontario, M5T2S8, Canada

NOT YET RECRUITING

The Hospital for Sick Children

Toronto, Ontario, Canada

RECRUITING

MeSH Terms

Conditions

Heart Arrest

Interventions

Endothelium-Dependent Relaxing Factors; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Vasodilator Agents; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Jamie Hutchison, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jamie Hutchison, MD

CONTACT

416-915-1857; jamie.hutchison@sickkids.ca

John Granton, MD

CONTACT

647-225-4485; john.granton@uhn.on.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The nitric oxide delivery device is covered with a secure shroud and Respiratory Therapists (RTs) are able to safely administer the nitric oxide or sham and document nitric oxide dose and their delivery device checks and monitor for adverse effects according to there clinical standard of care throughout the study intervention. The RTs also document whether there has been a unmasking of the intervention every 12 hours.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized controlled trial

Study Record Dates

• First Submitted: December 1, 2022
• First Posted: May 22, 2023
• Study Start: August 31, 2022
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2026
• Last Updated: November 30, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 6 months after publication
• Access Criteria: Requests for IPD will be reviewed by the study PI and SickKids institute. IPD will be provided to researchers interested in furthering academia and research development only. IPD requests may also be subjected to SickKids' institutional agreements/contracts. IPD mechanism of sharing and types of analysis/data shared will be directed and determined by SickKids' institutional research contracts requirements.

Locations

CA (4)