Inhaled Carbon Monoxide for Acute Respiratory Distress Syndrome (ARDS)

Not currently recruiting at 7 trial locations

Overseen By Rebecca Baron, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must not be taking: Inhaled vasodilators

Disqualifiers: Pregnancy, Recent MI, Severe hypoxemia, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether inhaled carbon monoxide (iCO) can safely help treat Acute Respiratory Distress Syndrome (ARDS), a serious condition where fluid accumulates in the lungs, making breathing difficult. Participants will inhale either iCO or medical air (as a placebo) to assess the treatment's effectiveness and safety. The trial targets individuals already on a ventilator due to ARDS. Those diagnosed with ARDS and currently intubated might be eligible to join. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does exclude participants using certain therapies like inhaled pulmonary vasodilators, so it's best to discuss your specific medications with the trial team.

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) has been tested for safety in patients with conditions like ARDS, including sepsis-induced ARDS. Studies have found that it can be administered accurately and is generally well-tolerated. In these studies, patients did not experience major side effects, suggesting that iCO appears safe at low doses. This finding is promising for its potential safety in treating ARDS. However, as with any treatment, discussing participation in a clinical trial with a doctor is important to understand all possible risks and benefits. ^{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 often include mechanical ventilation and supportive care, inhaled carbon monoxide is unique because it introduces a novel mechanism of action. This treatment involves inhaling carbon monoxide at low doses, which may help reduce inflammation and protect lung tissue from further damage. Researchers are excited about this approach because it offers a potentially safer and more targeted way to manage ARDS, with the possibility of improving outcomes without the invasive aspects of current therapies.

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

This trial will compare inhaled carbon monoxide (iCO) with medical air in patients with acute respiratory distress syndrome (ARDS). Studies have shown that iCO might protect the lungs in conditions like ARDS and sepsis. Previous research found that a low dose of iCO was safe and well-tolerated in patients with ARDS caused by sepsis. Experiments suggest that iCO could reduce lung injury due to its anti-inflammatory properties, potentially lessening lung damage. While more research is needed to confirm its benefits, early results are promising for treating ARDS. ^{1 2 3 6 7}

Who Is on the Research Team?

Rebecca Baron, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with ARDS, which is a severe lung condition. Participants must be intubated, have specific oxygenation and chest X-ray criteria, and not explained by heart failure. Exclusions include pregnancy, recent heart attacks or strokes, certain religious beliefs against blood transfusion, low hemoglobin levels, and unwillingness to follow the study's procedures.

Inclusion Criteria

ARDS is defined when all four of the following criteria are met:

A PaO2/FiO2 ratio ≤ 300 with at least 5 cm H2O positive end-expiratory airway pressure (PEEP)

Bilateral opacities on frontal chest radiograph (not fully explained by effusions, lobar/lung collapse, or nodules) within 1 week of a known clinical insult or new or worsening respiratory symptoms

Exclusion Criteria

Subjects who are Jehovah's Witnesses or are otherwise unable or unwilling to receive blood transfusions during hospitalization

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

Diffuse alveolar hemorrhage from vasculitis

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 medical air for up to 90 minutes daily for 3 days

1 week

Daily visits for 3 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 days

Regular monitoring visits

Long-term Follow-up

Participants are assessed for long-term outcomes such as hospital-free days and cognitive assessments

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Inhaled Carbon Monoxide

Trial Overview The study tests inhaled carbon monoxide (iCO) at 200 ppm versus medical air to see if iCO can safely treat ARDS. It's conducted across several hospitals and includes patients randomly assigned to either treatment without knowing which one they receive (partially double-blind).

How Is the Trial Designed?

Group I: Inhaled Carbon Monoxide Experimental Treatment 1 Intervention

Inhaled Carbon Monoxide at 200 ppm 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+

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+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Durham VA Medical Center

Collaborator

Trials

40

Recruited

9,300+

New York Presbyterian Brooklyn Methodist Hospital

Collaborator

Trials

21

Recruited

3,900+

Duke Regional Hospital

Collaborator

Trials

2

Recruited

2,400+

Duke Regional Hospital

Collaborator

Trials

2

Recruited

2,400+

U.S. Army Medical Research Acquisition Activity

Collaborator

Trials

26

Recruited

10,500+

Published Research Related to This Trial

In a multicenter trial involving 326 patients with acute respiratory distress syndrome (ARDS), intravenous salbutamol treatment was associated with increased 28-day mortality, with 34% of patients in the salbutamol group dying compared to 23% in the placebo group.

Due to safety concerns and the lack of benefit, the trial was stopped early, indicating that salbutamol is unlikely to be a safe or effective treatment for ARDS, and further studies on beta-agonists in this context are not recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-Agonist Lung injury TrIal-2 (BALTI-2): a multicentre, randomised, double-blind, placebo-controlled trial and economic evaluation of intravenous infusion of salbutamol versus placebo in patients with acute respiratory distress syndrome. Gates, S., Perkins, GD., Lamb, SE., et al.[2022]

Inhaled nitric oxide (iNO) therapy is more effective in ARDS patients with a greater amount of normal lung tissue surrounding small consolidated areas, as indicated by a significant correlation between the morphology of lung injury and the response to iNO.

Patients who did not respond to iNO therapy had larger, more coherently consolidated lung regions, suggesting that the distribution of lung injury plays a crucial role in the efficacy of iNO treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Computed tomographic criteria as expected effect to inhaled nitric oxide in patients with severe acute respiratory distress syndrome]. Röttgen, R., Busch, T., Lohbrunner, H., et al.[2020]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT03799874?tab=results

Safety and Efficacy Study of Inhaled Carbon Monoxide to ... See Delay Results Type in the Results Data ... Safety and Efficacy Study of Inhaled Carbon Monoxide to Treat Acute Respiratory Distress Syndrome (ARDS).

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6328240/

A phase I trial of low-dose inhaled carbon monoxide in ... A randomized controlled trial to investigate the safety and feasibility of low-dose iCO administration in mechanically ventilated patients with sepsis-induced ...

6. signavitae.com signavitae.com/articles/10.22514/sv.2022.041/htm

Therapeutic agents for ARDS Morbidity and mortality of ARDS remain high [3, 4], about 35–40%. Most surviving patients experience persistent and prolonged physical, mental and quality-of- ...

7. insight.jci.org insight.jci.org/articles/view/124039

A phase I trial of low-dose inhaled carbon monoxide in ... This is the first study to our knowledge to examine inhalation of low-dose iCO as a potential new therapy in critically ill patients. We show ...