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

NCT ID: NCT05868109

Last Updated: 2023-11-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-31

Study Completion Date

2026-01-31

Brief Summary

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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).

Detailed Description

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Background: Sudden cardiac arrest is a leading cause of death and neurological handicaps but there is no neuroprotective drug which improves outcome. Recently we discovered a blood biomarker of response to a neuroprotective therapy in our pre-clinical model of cerebral ischemia-reperfusion injury. Biomarkers will likely be used, in the future, to assess response to specific neuroprotective drugs and to help titrate drug dose and duration in individual patients.

Inhaled nitric oxide (iNO) has recently been shown to improve return of spontaneous circulation, survival, and neurological outcome in animal models of cardiac arrest. We have therefore started a pilot randomized controlled trial (RCT) and translational biology study of iNO in children and adults with cardiac arrest. This study will help us design future fully powered RCTs of iNO. We will use methods, from our pre-clinical model, to discover blood biomarkers of response to therapy.

Objectives: In patients with cardiac arrest: (1) Test the safety and feasibility of rapidly randomizing patients to iNO or sham during chest compressions, or shortly after return of circulation (ROC), either spontaneous or by extracorporeal life support. (2) Maintain blinding and measure study outcomes for 6 months post-arrest. (3) Use immunoassays, mass spectrometry and fluorometric assays to determine the differences in serum protein, nitrite, and nitrate biomarker concentrations between the two intervention groups and discover blood biomarkers of therapeutic response to iNO.

Patient population and sample size: Pediatric and adult (total N=40) patients with cardiac arrest admitted to 8 intensive care units (ICUs) at 4 hospitals: SickKids, University Health Network - Toronto General Hospital (TGH) and Toronto Western Hospital (TWH) and Unity Health - St. Michael's Hospital (SMH).

Methods: All patients meeting eligibility criteria will be enrolled, during chest compressions or within 6 hours of ROC, using deferred consent. Patients will be randomized to iNO or sham procedures, using a Redcap screening and randomization tool. Registered respiratory therapists will rapidly start the study gas using our blinded study apparatus. Inhaled NO will be started at a dose of 80 ppm via the endotracheal or tracheostomy tube during chest compressions and reduced to, or started at, 20 ppm after ROC. The iNO or sham procedures will be continued for 72 hours, and weaned off over 12 hours, or stopped earlier if the patient is extubated or dies. Using the Utstein data template for cardiac arrest research, we will collect data into an electronic case report form and Oracle database. Survival, cerebral performance category scores and quality of life scores will be assessed at 1 and 6 months following cardiac arrest. Data and documentation will be reviewed intermittently to ensure that we are compliant with Health Canada guidelines for drug trials.

Serum is being collected and banked at 4 time points following cardiac arrest. The concentrations of biomarkers will be measured and compared between the 2 intervention groups.

Progress: This study is funded by the Heart and Stroke Foundation of Canada.

Conditions

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Cardiac Arrest

Keywords

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Neuroprotection Nitric Oxide

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized controlled trial
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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Participants with Sham (no nitric oxide)

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

Group Type SHAM_COMPARATOR

Sham

Intervention Type 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.

Participants with Nitric Oxide

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

Group Type EXPERIMENTAL

inhaled nitric oxide (iNO)

Intervention Type 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.

Interventions

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inhaled nitric oxide (iNO)

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.

Intervention Type DRUG

Sham

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.

Intervention Type DRUG

Other Intervention Names

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INOMAX Sham intervention with no flow of inhaled nitric oxide to the patient

Eligibility Criteria

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Inclusion Criteria

To be eligible to participate in this study, an individual must meet all the following criteria:

1. Aged 1 day\* to 80 years on the day the study intervention is started
2. In-hospital or out-of-hospital CA with CPR \> 5 minutes
3. It is possible to randomize and start the iNO or sham during CPR or within 5 hours of ROC\*\*
4. 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).

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Unwitnessed cardiac arrest
2. Cardiac arrest due to birth asphyxia
3. Pre-arrest poor neurologic function\*
4. Already receiving iNO at the time of CA
5. 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
6. Any condition or diagnosis, in the opinion of the PI, Co-Investigators, or MRPs, in which iNO would be indicated as therapy post-arrest
7. CPR duration \> 45 minutes; if less than 18 years old, in-hospital CPR duration \> 60 minutes\*\*
8. Known pregnancy\*\*\*
9. 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
Minimum Eligible Age

1 Day

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Heart and Stroke Foundation of Canada

OTHER

Sponsor Role collaborator

The Hospital for Sick Children

OTHER

Sponsor Role lead

Responsible Party

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Jamie Hutchison

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jamie Hutchison, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Locations

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St. Michael's Hospital

Toronto, Ontario, Canada

Site Status NOT_YET_RECRUITING

Toronto General Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Toronto Western Hospital

Toronto, Ontario, Canada

Site Status NOT_YET_RECRUITING

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Jamie Hutchison, MD

Role: CONTACT

Phone: 416-915-1857

Email: [email protected]

John Granton, MD

Role: CONTACT

Phone: 647-225-4485

Email: [email protected]

Facility Contacts

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Andrew Baker, MD

Role: primary

John Granton, MD

Role: primary

Victoria McCredie, MD

Role: primary

Jamie Hutchison, MD

Role: primary

Other Identifiers

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1822

Identifier Type: -

Identifier Source: org_study_id