Inhaled Carbon Monoxide for ARDS

Not currently recruiting at 6 trial locations

Overseen By Mark A Perrella, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Brigham and Women's Hospital

Must not be taking: Inhaled vasodilators

Disqualifiers: Pregnancy, Severe cardiopulmonary disease, Stroke, others

Compensation: Varies

Number of Visits: 7

Duration: 3 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with acute respiratory distress syndrome (ARDS) caused by sepsis, a serious infection. Researchers aim to determine if inhaling small amounts of carbon monoxide, a gas that can affect breathing, is safe and effective for these patients. Participants will receive either inhaled carbon monoxide or a placebo, a harmless alternative, for three days. Suitable candidates for this trial have sepsis with breathing issues and are already on a ventilator. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are using inhaled pulmonary vasodilator therapy like nitric oxide or prostaglandins, you may not be eligible to participate.

Is there any evidence suggesting that inhaled carbon monoxide is likely to be safe for humans?

Research has shown that low-dose inhaled carbon monoxide (iCO) is generally safe and well-tolerated for people with sepsis-related acute respiratory distress syndrome (ARDS). In earlier studies, patients received precise amounts of iCO, demonstrating that this method was effective and did not cause serious issues.

The aim is to reach a carboxyhemoglobin (COHb) level of 6-8%, which requires careful management of carbon monoxide levels in the blood. This precise control helps prevent risks associated with carbon monoxide exposure, such as headaches or more severe symptoms. Overall, these findings suggest that iCO therapy is promising and safe for these patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Acute Respiratory Distress Syndrome (ARDS), which typically involve supportive care like mechanical ventilation and oxygen therapy, inhaled carbon monoxide (CO) offers a novel approach by utilizing a new mechanism of action. This experimental treatment leverages CO's potential anti-inflammatory properties and its ability to modulate immune responses, which could help protect lung tissue and improve recovery. Researchers are excited because, if successful, this approach could provide a targeted, non-invasive treatment option that works in a fundamentally different way by potentially reducing inflammation and promoting healing directly in the lungs.

What evidence suggests that inhaled carbon monoxide might be an effective treatment for ARDS?

Research has shown that inhaled carbon monoxide (iCO), which participants in this trial may receive, might help treat breathing problems caused by sepsis, known as acute respiratory distress syndrome (ARDS). Some studies found that a low dose of iCO is safe and well-tolerated in patients with this condition. In lab tests, carbon monoxide protected against lung damage and sepsis. The goal is to use the right amount of iCO to achieve specific blood levels without causing harm. These early results suggest that iCO could be a promising treatment for ARDS. ^{1 2 3 5 6}

Who Is on the Research Team?

Rebecca Baron, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

Adults with sepsis-induced ARDS, meeting specific criteria including a PaO2/FiO2 ratio ≤ 300 and requiring positive pressure ventilation. Excluded are those under 18, pregnant or breastfeeding women, patients without arterial/central lines, those not expected to survive 24 hours, and others with certain medical conditions.

Inclusion Criteria

I have sepsis with organ dysfunction due to an infection.

I have severe lung condition not caused by heart failure, needing a ventilator.

Your Sequential Organ Failure Assessment (SOFA) score has increased by 2 or more from the starting point.

Exclusion Criteria

No arterial line or central line/no intent to place an arterial or central line

You are a Jehovah's Witness or cannot or do not want to receive a blood transfusion while in the hospital.

I do not have severe heart, lung conditions, recent major surgeries, or participated in another drug study recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive inhaled carbon monoxide or placebo for up to 90 minutes daily for 3 days

3 days

Daily visits for 3 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

Regular assessments on days 1-5, 7, 14, and 28

Long-term Follow-up

Participants are assessed for cognitive and other long-term outcomes

3-6 months

Telephone interviews at 3 and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Inhaled Carbon Monoxide

Trial Overview The trial tests personalized doses of inhaled Carbon Monoxide (200-500 ppm) to achieve COHb levels of 6-8% against inhaled medical air for safety and effectiveness in treating sepsis-induced ARDS. It's randomized and partially double-blind.

How Is the Trial Designed?

Group I: Inhaled Carbon Monoxide Experimental Treatment 1 Intervention

Inhaled Carbon Monoxide at CFK equation-determined personalized dose (200-500 ppm to achieve a COHb level of 6-8%) for up to 90 minutes daily for 3 days.

Group II: Medical air Placebo Group 1 Intervention

Inhaled Medical Air for up to 90 minutes daily for 3 days.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03799874

Safety and Efficacy Study of Inhaled Carbon Monoxide to ... The purpose of this study is to assess the safety and efficacy of low dose inhaled carbon monoxide (iCO) therapy in mechanically ventilated patients with ARDS.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30518685/

A phase I trial of low-dose inhaled carbon monoxide in sepsis ... Conclusion: Precise administration of low-dose iCO is feasible, well-tolerated, and appears to be safe in patients with sepsis-induced ARDS.

3. clinicaltrial.be clinicaltrial.be/fr/details/6038?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Safety and Efficacy Study of Inhaled Carbon Monoxide to T... CO has been shown to be protective in experimental models of acute lung injury (ALI) and sepsis. Furthermore, multiple human studies have ...

4. nature.com nature.com/articles/s41392-025-02127-9

Advances in acute respiratory distress syndrome According to several small sample studies, the probability that a COVID-19 patient will suffer from ARDS is 40–65%, with a mortality rate ...

5. respiratory-therapy.com respiratory-therapy.com/disorders-diseases/critical-care/acute-disorders/carbon-monoxide-poisoning-antidote-in-development/

Carbon Monoxide Poisoning Antidote in Development | RT Faster and Safer Than Oxygen Therapy – In mice, the antidote cleared half the carbon monoxide from blood in under one minute, compared to over ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5363978/

Carbon Monoxide Poisoning: Pathogenesis, Management ... The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1 to 3%.