Inhaled Nitric Oxide for Respiratory Failure in Obesity

Overseen By Maurizio Cereda, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must be taking: Neuromuscular blockers

Must not be taking: Pulmonary vasodilators

Disqualifiers: Pregnancy, Prisoner, Pneumothorax, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this clinical trial is to learn about the effects of inhaled nitric oxide on oxygenation and lung perfusion in participants with severe obesity who have acute hypoxemic respiratory failure and are on mechanical ventilation The main questions it aims to answer are: 1. In acute hypoxemic respiratory failure, what are the effects of inhaled nitric oxide on oxygenation in participants with severe obesity compared to participants with normal body weight. 2. In acute hypoxemic respiratory failure, what are the effects of inhaled nitric oxide on lung perfusion and heart function in participants with severe obesity compared to participants with normal body weight. 3. In acute hypoxemic respiratory failure, does severe obesity impact nitric oxide signaling pathways? Participants with acute hypoxemic respiratory failure will be exposed to inhaled nitric oxide (20 ppm) while being clinically monitored.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot have used inhaled or oral pulmonary vasodilatory therapy within 24 hours before joining the study.

Is inhaled nitric oxide generally safe for humans?

Inhaled nitric oxide (iNO) is generally considered safe with limited side effects when used in humans, as shown in studies involving critically ill patients and newborns with respiratory issues. Some potential adverse events include low blood pressure and heart rhythm changes, but these are manageable with proper medical supervision. ^{1 2 3 4 5}

How is the drug inhaled nitric oxide unique for treating respiratory failure in obesity?

Inhaled nitric oxide is unique because it is administered directly into the lungs to improve oxygenation, which can be particularly beneficial for patients with severe respiratory failure. Unlike other treatments, it specifically targets the lungs to reduce pulmonary arterial hypertension (high blood pressure in the lungs) and improve oxygen levels, although it does not necessarily improve survival rates. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Inhaled Nitric Oxide for respiratory failure in obesity?

Inhaled nitric oxide (iNO) can help improve oxygen levels in patients with severe respiratory or heart failure, but it has not been shown to improve survival rates. It is often used as a rescue treatment for severe breathing problems in critical care settings. ^{6 7 10 11 12}

Are You a Good Fit for This Trial?

This trial is for patients with severe obesity who are experiencing acute hypoxemic respiratory failure and require mechanical ventilation. Specific eligibility criteria details are not provided, but typically participants would need to meet certain health conditions.

Inclusion Criteria

Patients with acute hypoxemic respiratory failure must have a PaO2/FiO2 ratio of 300 mmHg or less

Patients with acute hypoxemic respiratory failure must have an arterial and central venous catheter for blood gas measurement

Controls without acute hypoxemic respiratory failure must have a PaO2/FiO2 ratio greater than 300 mmHg

Exclusion Criteria

Controls without acute hypoxemic respiratory failure must not have suspected pregnancy, be pregnant, or be less than six weeks postpartum

My Methemoglobin level is below 3%.

I do not use a pacemaker or internal defibrillator.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants with acute hypoxemic respiratory failure receive inhaled nitric oxide (20 ppm) for 15 minutes while being clinically monitored

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in intrapulmonary shunt, regional pulmonary perfusion, gas exchange, nitric oxide activity, and right ventricular systolic pressure

1 day

1 visit (in-person)

Biomarker Analysis

Biomarkers of nitric oxide signaling dysfunction are measured in participants with and without acute hypoxemic respiratory failure

Single time point

What Are the Treatments Tested in This Trial?

Interventions

• Inhaled Nitric Oxide

Trial Overview The study tests the effects of inhaled nitric oxide on oxygen levels, lung blood flow, and heart function in severely obese patients with low oxygen levels due to respiratory failure compared to those with normal weight.

How Is the Trial Designed?

Group I: Acute hypoxemic respiratory failure Experimental Treatment 1 Intervention

Participants (n = 40) with acute hypoxemic respiratory failure will receive inhaled nitric oxide (20 ppm) for 15 min.

Group II: Participants without acute hypoxemic respiratory failure Active Control 1 Intervention

Participants (n = 20) without acute hypoxemic respiratory failure will not receive inhaled nitric oxide

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?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

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]

Citations

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

Nitric oxide delivery by neonatal noninvasive respiratory support devices. [2015]

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

Nitric oxide delivery during high-frequency oscillatory ventilation. [2016]

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

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

5. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical indication for use and outcomes after inhaled nitric oxide therapy. [2022]

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

A Stewardship Program to Optimize the Use of Inhaled Nitric Oxide in Pediatric Critical Care. [2019]

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

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

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

Evidence-based clinical practice guideline: inhaled nitric oxide for neonates with acute hypoxic respiratory failure. [2018]

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

Nitric oxide: Clinical applications in critically ill patients. [2023]

10. Norway pubmed.ncbi.nlm.nih.gov

Use of inhaled nitric oxide in the new born period: results from the European Inhaled Nitric Oxide Registry. [2013]

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

Inhaled nitric oxide therapy in adults: European expert recommendations. [2022]

12. 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]