Inhaled Nitric Oxide for Cardiac Arrest

(iNOCAPA Trial)

Recruiting at 3 trial locations

Overseen By John Granton, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: The Hospital for Sick Children

Disqualifiers: Unwitnessed arrest, Birth asphyxia, Poor neurologic, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 3.5 days

40 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Inhaled Nitric Oxide for cardiac arrest?

Inhaled nitric oxide (iNO) has been shown to improve outcomes in animal studies when given during cardiopulmonary resuscitation (CPR) after cardiac arrest, increasing the success of resuscitation and improving survival rates. Additionally, iNO is known to improve oxygenation and reduce the need for extracorporeal membrane oxygenation (ECMO) in newborns with severe respiratory failure. ^{1 2 3 4 5}

How is the drug inhaled nitric oxide unique for treating cardiac arrest?

Inhaled nitric oxide (iNO) is unique because it is administered directly into the lungs to improve oxygenation and reduce pulmonary arterial pressure, which is different from other treatments for cardiac arrest that may not target the lungs directly. While it has shown benefits in animal models for cardiac arrest, its impact on humans with cardiac arrest is still being studied. ^{2 3 4 6 7}

Research Team

Jamie Hutchison, MD

Principal Investigator

The Hospital for Sick Children

Eligibility Criteria

This trial is for children and adults aged 1 day to 80 years who've had a cardiac arrest and are on mechanical ventilation in the ICU. They must be able to start treatment during CPR or within 5 hours after circulation returns. Excluded are those with pre-arrest poor brain function, already on iNO, certain heart conditions, long CPR duration (>45 minutes), known pregnancy, or terminal illness.

Inclusion Criteria

I can start the trial treatment during CPR or within 5 hours after my heart starts again.

I am currently on a ventilator in the ICU.

I had a cardiac arrest and received CPR for more than 5 minutes.

Exclusion Criteria

I need iNO therapy after a cardiac arrest.

Known pregnancy

I had a heart attack that no one saw.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 6 hours

1 visit (in-person)

Treatment

Participants receive inhaled nitric oxide or sham treatment during chest compressions or shortly after return of circulation for 72 hours, followed by a 12-hour weaning period

3.5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 1 and 6 months following cardiac arrest

6 months

Multiple visits (in-person and virtual)

Biomarker Analysis

Blood samples are collected and analyzed for biomarkers at multiple time points post-enrollment

7 days

Treatment Details

Interventions

• Inhaled Nitric Oxide
• Sham

Trial Overview The study tests if inhaling nitric oxide (iNO) helps patients during or just after a cardiac arrest compared to a sham (fake treatment). It's randomized and double-blind, meaning neither the participants nor the researchers know who gets real iNO until after the results are collected.

Participant Groups

Group I: Participants with Nitric Oxide Experimental Treatment 1 Intervention

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

Group II: Participants with Sham (no nitric oxide) Placebo Group 1 Intervention

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

Inhaled Nitric Oxide is already approved in United States, European Union for the following indications:

Approved in United States as INOmax for:

• Hypoxic respiratory failure
• Pulmonary hypertension

Approved in United States as Genosyl for:

• Hypoxic respiratory failure
• Pulmonary hypertension

Approved in European Union as INOmax for:

• Persistent pulmonary hypertension of the newborn
• Acute hypoxic respiratory failure

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Heart and Stroke Foundation of Canada

Collaborator

Trials

131

Recruited

72,600+

Findings from Research

Inhaled nitric oxide (iNO) can improve oxygenation in critically ill patients with pulmonary hypertension and respiratory failure, but it does not improve survival rates, as shown in a study of 215 patients from 2004 to 2009.

Key predictors of mortality in patients receiving iNO include worsening Sequential Organ Failure Assessment scores, higher Charlson Comorbidity Scores, and increased methaemoglobin levels, indicating that while iNO may help with oxygenation, its use as a routine treatment in severe cases is not justified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

'Safe' methaemoglobin concentrations are a mortality risk factor in patients receiving inhaled nitric oxide. Rolley, L., Bandeshe, H., Boots, RJ.[2019]

Inhaled nitric oxide (iNO) significantly improved oxygen levels in patients with severe hypoxemia, with arterial oxygen partial pressure (PaO2) increasing from 60.7 to 72.3 mm Hg after treatment (P=.008).

The use of iNO allowed for safe transport of patients to a tertiary care center, with 60.2% of those treated surviving to discharge, compared to a 50% survival rate in patients transported without iNO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide to improve oxygenation for safe critical care transport of adults with severe hypoxemia. Teman, NR., Thomas, J., Bryner, BS., et al.[2020]

Inhaled nitric oxide (iNO) can be safely managed by trained nurses during the transport of critically ill patients, as demonstrated by a study involving patients transported from March 2020 to August 2022.

Out of the patients studied, only 16.7% experienced hypotension, which was manageable and resolved with medication adjustments, while no serious adverse events like worsening hypoxemia or cardiac arrest were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Nurse-Managed Inhaled Nitric Oxide During Critical Care Interfacility Transport. Troncoso, R., Garfinkel, EM., Kaul, K., et al.[2023]

Inhaled nitric oxide (iNO) significantly improved arterial oxygen levels in 73% of neonates treated early compared to 37% in the control group, indicating its efficacy in enhancing oxygenation in infants with severe respiratory failure.

However, starting iNO treatment earlier (at an oxygenation index of 15 to 25) did not lead to a reduction in the rates of death or the need for ECMO compared to starting treatment later, suggesting that timing of administration may not impact these critical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of early versus standard inhaled nitric oxide therapy in term and near-term newborn infants with hypoxic respiratory failure. Konduri, GG., Solimano, A., Sokol, GM., et al.[2019]

Inhaled nitric oxide (iNO) at 20 ppm during CPR significantly improved return of spontaneous circulation (ROSC) rates and increased mean arterial pressure in a rat model of cardiac arrest, suggesting enhanced resuscitation outcomes.

The use of 20 ppm iNO also led to better neurological recovery and increased 7-day survival rates compared to control, indicating its potential as a beneficial intervention following cardiac arrest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief inhalation of nitric oxide increases resuscitation success and improves 7-day-survival after cardiac arrest in rats: a randomized controlled animal study. Brücken, A., Derwall, M., Bleilevens, C., et al.[2018]

In a pilot study involving 20 adults with in-hospital cardiac arrest (IHCA), the use of inhaled nitric oxide (iNO) was associated with a significantly higher survival rate to discharge (35%) compared to controls (11%).

While iNO improved survival rates, it did not show a significant difference in favorable neurologic outcomes when compared to controls, indicating that while iNO may help patients survive longer, it does not necessarily improve brain function after cardiac arrest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide in adults with in-hospital cardiac arrest: A feasibility study. Patel, JK., Schoenfeld, E., Hou, W., et al.[2022]

The implementation of clinical guidelines for inhaled nitric oxide (iNO) therapy in a pediatric intensive care unit led to a significant reduction in the duration of iNO treatment, from a median of 162 hours to 76 hours, without compromising patient care.

Following the guidelines, there was a notable cost savings of $4,600 per patient, demonstrating that standardized protocols can enhance efficiency and reduce unnecessary expenses in iNO therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Quality Improvement Initiative to Standardize Use of Inhaled Nitric Oxide in the PICU. Karsies, TJ., Evans, L., Frost, R., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

'Safe' methaemoglobin concentrations are a mortality risk factor in patients receiving inhaled nitric oxide. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide to improve oxygenation for safe critical care transport of adults with severe hypoxemia. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Safety of Nurse-Managed Inhaled Nitric Oxide During Critical Care Interfacility Transport. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

A randomized trial of early versus standard inhaled nitric oxide therapy in term and near-term newborn infants with hypoxic respiratory failure. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Brief inhalation of nitric oxide increases resuscitation success and improves 7-day-survival after cardiac arrest in rats: a randomized controlled animal study. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide in adults with in-hospital cardiac arrest: A feasibility study. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A Quality Improvement Initiative to Standardize Use of Inhaled Nitric Oxide in the PICU. [2022]