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

Primary Purpose

Cardiac Arrest

Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
inhaled nitric oxide (iNO)
Sham
Sponsored by
The Hospital for Sick Children
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiac Arrest focused on measuring Neuroprotection, Nitric Oxide

Eligibility Criteria

1 Day - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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). Exclusion Criteria: 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** 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

Sites / Locations

  • St. Michael's Hospital
  • Toronto General HospitalRecruiting
  • Toronto Western Hospital
  • The Hospital for Sick ChildrenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Experimental

Arm Label

Participants with Sham (no nitric oxide)

Participants with Nitric Oxide

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Monitor recruitment rate
Recruitment rate is the rate of enrolment/randomization/consent divided by the number of eligible patients which meet all inclusion criteria and have no exclusion criteria.
Monitor time to randomization of eligible patients
Timing of randomization. The time of randomization following onset of cardiac arrest will be recorded. We will attempt to speed up this time using simulations with study and clinical personnel and by debriefing each enrolled patient with the teams involved. We will attempt to enrol some patients who have a cardiac arrest in the ICU during chest compressions and for those patients enrolled following return of circulation, the timeframe is a maximum of 5 hours.
Monitor masking and unmasking events
Number of unblinding instances. The study apparatus (inhaled nitric oxide gas delivery device) has a secure cover that only the Respiratory Therapists are trained to open. The RTs will record any unblinding events which may include breaking/cutting of the cover ties and opening of the apparatus cover by clinical personnel other than RTs. The RTs will record and sign 'unblinding yes/no' into their masked RT study case report form on each RT clinical shift and study Research Coordinators will enter this data into the study electronic database. We will monitor unblinding events in real time and attempt to prevent these from happening.
Study follow-up rates
We will measure outcomes at 1 and 6 months following cardiac arrest as outlined in more detail below. Number of completed study outcomes at 6 months following cardiac arrest will be followed in real time and we will attempt to maximize follow-up rates.

Full Information

First Posted
December 1, 2022
Last Updated
May 11, 2023
Sponsor
The Hospital for Sick Children
Collaborators
Heart and Stroke Foundation of Canada
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1. Study Identification

Unique Protocol Identification Number
NCT05868109
Brief Title
Inhaled Nitric Oxide for Cardiac Arrest in Pediatrics and Adults (iNOCAPA)
Acronym
iNOCAPA
Official Title
Inhaled Nitric Oxide for Cardiac Arrest in Pediatrics and Adults (iNOCAPA): A Pilot Randomized Controlled Trial and Translational Biology Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 31, 2022 (Actual)
Primary Completion Date
January 31, 2025 (Anticipated)
Study Completion Date
January 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Hospital for Sick Children
Collaborators
Heart and Stroke Foundation of Canada

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Arrest
Keywords
Neuroprotection, Nitric Oxide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized controlled trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Participants with Sham (no nitric oxide)
Arm Type
Sham Comparator
Arm Description
The mechanical ventilator circuit of the study participants are attached to the inhaled nitric oxide delivery device but nitric oxide is not delivered.
Arm Title
Participants with Nitric Oxide
Arm Type
Experimental
Arm Description
The mechanical ventilator circuit of the study participants are attached to the inhaled nitric oxide delivery device and nitric oxide is delivered.
Intervention Type
Drug
Intervention Name(s)
inhaled nitric oxide (iNO)
Intervention Description
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
Intervention Name(s)
Sham
Intervention Description
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.
Primary Outcome Measure Information:
Title
Drug Procedural Feasibility
Description
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.
Time Frame
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.
Title
Drug Procedural Feasibility
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Monitor recruitment rate
Description
Recruitment rate is the rate of enrolment/randomization/consent divided by the number of eligible patients which meet all inclusion criteria and have no exclusion criteria.
Time Frame
For study duration, approximately 2 years.
Title
Monitor time to randomization of eligible patients
Description
Timing of randomization. The time of randomization following onset of cardiac arrest will be recorded. We will attempt to speed up this time using simulations with study and clinical personnel and by debriefing each enrolled patient with the teams involved. We will attempt to enrol some patients who have a cardiac arrest in the ICU during chest compressions and for those patients enrolled following return of circulation, the timeframe is a maximum of 5 hours.
Time Frame
At study enrollment during the 2 years of study recruitment.
Title
Monitor masking and unmasking events
Description
Number of unblinding instances. The study apparatus (inhaled nitric oxide gas delivery device) has a secure cover that only the Respiratory Therapists are trained to open. The RTs will record any unblinding events which may include breaking/cutting of the cover ties and opening of the apparatus cover by clinical personnel other than RTs. The RTs will record and sign 'unblinding yes/no' into their masked RT study case report form on each RT clinical shift and study Research Coordinators will enter this data into the study electronic database. We will monitor unblinding events in real time and attempt to prevent these from happening.
Time Frame
During the 2 year study duration and data analysis.
Title
Study follow-up rates
Description
We will measure outcomes at 1 and 6 months following cardiac arrest as outlined in more detail below. Number of completed study outcomes at 6 months following cardiac arrest will be followed in real time and we will attempt to maximize follow-up rates.
Time Frame
For study follow-up, approximately 2.5 years.
Other Pre-specified Outcome Measures:
Title
Return of spontaneous circulation (ROSC)
Description
Rate of ROSC, for participants in whom the iNO or sham procedure is initiated during chest compressions and cardiopulmonary resuscitation.
Time Frame
Duration of study enrollment, approximately 2 years.
Title
Survival at hospital discharge
Description
Survival to hospital discharge, 1 month, and 6 months following cardiac arrest.
Time Frame
For duration of study follow-up, approximately 2 years and 6 months.
Title
Cerebral performance category score
Description
Cerebral Performance Category (CPC) or Pediatric Cerebral Performance Category (PCPC) scores, for adults and children respectively, at 1 month, and 6 months following cardiac arrest. CPC scores range from 1 to 5 with 1 indicating good outcome, 4 indicating persistent vegetative state and 5 indicating death. PCPC scores range from 1 to 6, with 1 indicating good cerebral performance, 5 indicating persistent vegetative state and 6 indicating death.
Time Frame
For duration of study follow-up, approximately 2 years and 6 months.
Title
Quality of Life Score
Description
Pediatric Quality of Life (PedsQL) scores (includes 2 adult versions) at 1 month, and 6 months following cardiac arrest. Results are reverse scored and transformed into a scale with a range of 0 to 100, with higher scores indicate better health related quality of life.
Time Frame
For duration of study follow-up, approximately 2 years and 6 months.
Title
Quality of life after brain injury
Description
Quality Of Life after Brain Injury-Overall Scale (QOLIBRI-OS, for adults only) at 1 month, and 6 months following cardiac arrest. QOLIBRI scores are reported on a 0 to 100 scale, with 0 indicating worst possible quality of life and 100 indicating best possible quality of life.
Time Frame
For duration of study follow-up, approximately 2 years and 6 months.
Title
Blood protein biomarkers
Description
Blood will be sampled, and the serum separated and divided into aliquots and banked at 4 time points following enrolment. These time points are within 4 hours following enrolment and with AM clinical blood sampling on Day 2, 4 and 7. Day 1 is defined as the 24 hour period from 00:01 to 24:00 hours during which the patient was enrolled. At the end of the study, a panel of brain specific and inflammatory proteins will be measured in serum samples and their concentrations compared between intervention groups. We will also perform shotgun proteomics using untargeted mass spectrometry and compare blood peptide/protein concentrations from Day 2 samples between the 2 intervention groups. Promising peptides/proteins that may indicate response to iNO will then be measured, using targeted mass spectrometry in serum samples from all 4 time points to determine the time course of these peptides/proteins.
Time Frame
Bloods sampled and banked for up to 7 days post-cardiac arrest. Biomarker measurements will be done after we have recruited 40 patients into the study. i.e. at approximately 2 years after the start of study enrolment.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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). Exclusion Criteria: 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** 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jamie Hutchison
Phone
416-813-7654
Ext
304549
Email
jamie.hutchison@sickkids.ca
Facility Information:
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B1W8
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew Baker, MD
Phone
(416) 864-5559
Email
Andrew.Baker@unityhealth.to
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G2C4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Granton, MD
Phone
416-340-4485
Email
john.granton@uhn.ca
Facility Name
Toronto Western Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T2S8
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Victoria McCredie, MD
Email
victoria.mccredie@uhn.ca
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jamie Hutchison, MD
Phone
416-813-7654
Ext
304549
Email
jamie.hutchison@sickkids.ca

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All de-identified individual participant data (IPD) that underlie results in a publication will be shared upon request. The study protocol, and statistical analysis plan will be shared starting 6 months after publication upon request in writing. 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
IPD Sharing Time Frame
6 months after publication
IPD Sharing 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.

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

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