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

Cardiac Arrest Clinical Trial

Official title: Inhaled Nitric Oxide for Cardiac Arrest in Pediatrics and Adults (iNOCAPA): A Pilot Randomized Controlled Trial and Translational Biology Study

Status Recruiting

Clinical Trial 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).

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Cardiac Arrest
• Heart Arrest

• NCT number: NCT05868109
• Study type: Interventional
• Source: The Hospital for Sick Children
• Contact: Jamie Hutchison, MD
• Phone: 416-915-1857
• Email: jamie.hutchison@sickkids.ca
• Status: Recruiting
• Phase: Phase 2
• Start date: August 31, 2022
• Completion date: January 31, 2026