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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how inhaled nitric oxide might assist people with severe obesity who struggle to breathe due to acute hypoxemic respiratory failure and require a breathing machine. Researchers aim to determine if this treatment enhances lung and heart function in these patients compared to those of normal body weight. The trial seeks participants currently in intensive care with breathing difficulties and using a ventilator. As an unphased trial, this study provides a unique opportunity to contribute to important research that could enhance future treatments for respiratory failure.

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.

What prior data suggests that inhaled nitric oxide is safe for participants with respiratory failure in obesity?

Research shows that inhaled nitric oxide (iNO) is generally safe for individuals with breathing problems. Studies have found that it can improve oxygen levels by addressing a condition where the blood doesn't receive enough oxygen in the lungs. This means iNO can enhance lung function to better oxygenate the blood.

In terms of safety, hospitals already use inhaled nitric oxide for certain lung issues, indicating its safety. Reports of minor side effects exist, but these are usually not serious. Most individuals tolerate the treatment well without major problems.

This trial targets individuals with severe obesity and breathing problems. Based on past research, inhaled nitric oxide appears to be a safe option for improving lung function. For personalized information, discussing concerns with the trial team is recommended. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about inhaled nitric oxide for respiratory failure because it offers a unique approach compared to other treatments like mechanical ventilation or supplemental oxygen. Inhaled nitric oxide works by directly relaxing the blood vessels in the lungs, improving oxygenation quickly and efficiently. Unlike standard treatments, which can take longer to show improvement, this method has the potential to deliver rapid results in just minutes. Additionally, its targeted delivery means it can minimize side effects often associated with more systemic therapies.

What evidence suggests that inhaled nitric oxide is effective for acute hypoxemic respiratory failure in severe obesity?

In this trial, participants with acute hypoxemic respiratory failure will receive inhaled nitric oxide to assess its effectiveness in improving lung function. Studies have shown that inhaled nitric oxide can aid individuals with breathing problems by enhancing lung performance, facilitating oxygen entry into the blood. This treatment has been used successfully in other conditions, such as low oxygen levels in the blood, where it improves lung function. While research supports its use for enhancing lung function, results can vary based on individual health and body type. Researchers are still studying its effectiveness and impact on the heart and lungs in individuals with severe obesity. ^{1 2 4 6 7}

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 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) 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]

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]

Citations

1. withpower.com withpower.com/trial/inhaled-nitric-oxide-for-respiratory-failure-in-obesity-7e693

Inhaled Nitric Oxide for Respiratory Failure in Obesity 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10765403/

High-Dose Inhaled Nitric Oxide in Acute Hypoxemic ... The beneficial effects of inhaled NO therapy have been attributed to its ability to reduce intrapulmonary shunting (6), resulting in improved oxygenation for ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa060442

Early Inhaled Nitric Oxide Therapy in Premature Newborns ... Previous studies suggested that inhaled nitric oxide can improve gas exchange in premature newborns with hypoxemia caused by the respiratory distress syndrome ...

4. fda.gov fda.gov/media/79633/download

20845 Nitric Oxide Statistical PREA Therefore, the evidence from this study is insufficient to support the efficacy of iNOmax (nitric oxide) for the treatment of chronic lung.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00922532

Inhaled Nitric Oxide (INO) In Hypoxic Respiratory Failure This Phase 3, Double-blind, Randomized, Placebo controlled, multicenter study is to confirm the efficacy of inhaled nitric oxide for the management of hypoxic ...

6. jonathanlilab.bwh.harvard.edu jonathanlilab.bwh.harvard.edu/wp-content/uploads/2023/10/DiFenzaBerra-Inhaled-NO-ATSJ-2023.pdf

High-Dose Inhaled Nitric Oxide in Acute Hypoxemic ... The beneficial effects of inhaled NO therapy have been attributed to its ability to reduce intrapulmonary shunting (6),resulting in improved oxygenation for the ...

7. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/552416

Inhaled Nitric Oxide in Severe Obesity - Carebox Connect 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 ...