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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of inhaled nitric oxide (iNO) during or shortly after CPR to assist individuals who have experienced cardiac arrest (when the heart stops beating). The researchers aim to determine if iNO can be safely and effectively administered during these critical moments and how it affects certain blood markers compared to a placebo. Participants will receive either iNO or a non-active treatment to compare results. Suitable candidates for this trial include those who have experienced cardiac arrest, received CPR for more than 5 minutes, and are on a ventilator in an intensive care unit. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that inhaled nitric oxide is likely to be safe for humans?

Research has shown that inhaled nitric oxide (iNO) is generally safe for people. One study linked iNO to higher survival rates for patients who experienced cardiac arrest in the hospital, suggesting its potential safety in emergencies. Another study with animals demonstrated that iNO improved blood flow and recovery after prolonged cardiac arrest, offering hope for its safety in humans as well.

While these results are encouraging, ongoing trials continue to test them. As this study is in an early phase, it aims to gather more information about the treatment's safety and effects. Researchers still need to understand how well people can tolerate iNO, but early results are positive. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cardiac arrest, which often involve CPR and defibrillation, inhaled nitric oxide offers a novel approach by potentially improving blood flow and oxygen delivery directly to the brain and heart. This treatment is unique because it uses a gas delivered through a ventilator, allowing for targeted therapy that might reduce damage after cardiac arrest. Researchers are excited about inhaled nitric oxide because it could enhance recovery outcomes by working quickly and efficiently in emergency situations.

What evidence suggests that inhaled nitric oxide might be an effective treatment for cardiac arrest?

Research has shown that inhaled nitric oxide (iNO), which participants in this trial may receive, can aid recovery after a heart attack. One study found that iNO protects brain cells and increases survival chances. Another study discovered that iNO reduces blood cell activity and nerve damage, leading to better survival and brain health post-heart attack. Animal studies also suggest that iNO improves lung blood flow and aids recovery after a prolonged heart attack. These findings indicate that iNO might effectively enhance recovery following a heart attack. ^{1 2 6 7 8}

Who Is on the Research Team?

Jamie Hutchison, MD

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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]

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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3199136/

Inhaled Nitric Oxide Improves Outcomes After Successful ... Inhaled NO prevents neuronal apoptosis after cardiac arrest and CPR ... The ability of NO breathing to improve outcomes after cardiac arrest when begun ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1089860322000684

Inhaled nitric oxide improves post-cardiac arrest outcomes ... The current study revealed that iNO after ROSC prevented CA/CPR-induced platelet activation and neurodegeneration and improved survival after CA/CPR.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05868109

NCT05868109 | Inhaled Nitric Oxide for Cardiac Arrest in ... Inhaled nitric oxide (iNO) has recently been shown to improve return of spontaneous circulation, survival, and neurological outcome in animal models of cardiac ...

4. ahajournals.org ahajournals.org/doi/10.1161/circ.132.suppl_3.12202

Abstract 12202: Inhaled Nitric Oxide Improves Artificial ... Conclusions: In a model of prolonged cardiac arrest, the administration of 20ppm iNO during and following iCPR improved transpulmonary bloodflow ...

5. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-015-1050-2

Inhaled nitric oxide improves transpulmonary blood flow and ... Inhaled nitric oxide improves transpulmonary blood flow and clinical outcomes after prolonged cardiac arrest: a large animal study. Matthias ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1089860321000604

Inhaled nitric oxide in adults with in-hospital cardiac arrest In this pilot study, iNO was associated with significantly higher rates of survival to discharge but not favorable neurologic outcome among patients with IHCA ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4570752/

Inhaled nitric oxide improves transpulmonary blood flow ... Inhaled nitric oxide improves transpulmonary blood flow and clinical outcomes after prolonged cardiac arrest: a large animal study · Abstract. Introduction.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03079102?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(INOVENT))&rank=8

Inhaled Nitric Oxide After Out-of-Hospital Cardiac Arrest Statistical Analysis Plan Continuous data will be compared using t-tests and repeated measures ANOVA to compare between iNO and placebo groups at multiple times ...