Safety and Efficacy Study of Inhaled Carbon Monoxide to Treat Acute Respiratory Distress Syndrome (ARDS)

NCT03799874 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2018P002051CDMRP-PR171025, W81XWH1810667
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 7

Brief Summary

This study will be a multi-center, prospective, randomized, partially double-blind, placebo-controlled Phase II clinical trial of inhaled CO (iCO) for the treatment of ARDS. The trial will be conducted at 7 tertiary care medical centers including Weill Cornell Medicine/NewYork-Presbyterian Hospital, Brigham and Women's Hospital (BWH), Massachusetts General Hospital (MGH), Duke University Hospital, Durham Veterans Administration Medical Center, New York-Presbyterian Brooklyn Methodist Hospital, and Duke Regional Hospital. The purpose of this study is to evaluate the safety, tolerability, and efficacy of inhaled carbon monoxide (iCO) for the treatment of ARDS and to examine the biologic readouts of low dose iCO therapy in patients with ARDS

Conditions

Acute Respiratory Distress Syndrome

Outcome Measures

Primary Outcomes (2)

• Primary Safety Outcome: Number of Pre-specified Administration-related Adverse Events.

  Safety of inhaled CO, defined by the incidence of pre-specified administration-related AEs (as defined below) and spontaneously reported AEs through study day 7. 1. Acute MI within 48 hours of study drug administration 2. Acute cerebrovascular accident (CVA) within 48 hours of study drug administration 3. New onset atrial or ventricular arrhythmia requiring DC cardioversion within 48 hours of study drug administration 4. Increased oxygenation requirements defined as: an increase in FiO2 of ≥ 0.2 AND increase in PEEP ≥ 5 cm H2O within 6 hours of study drug administration 5. Increase in COHb ≥ 10% 6. Increase in lactate by ≥ 2 mmol/L within 6 hours of study drug administration

  7 days

• Primary Efficacy Outcome: Change in Mitochondrial DNA (mtDNA) Level From Day 1 to Day 5

  Mitochondrial DNA (mtDNA) plasma levels will be measured by quantitative PCR of human NADH dehydrogenase 1. The number presented is the percentage average difference from beginning to end of treatment. Limited number of measurements prevents variance analyses; therefore we present the data from the subjects available in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.

  5 days

Secondary Outcomes (7)

• Lung Injury Score (LIS) on Days 1-5, and on Days 1-7

  7 days

• Percent Change in PaO2/FiO2 Ratio on Days 1-5, and on Days 1-7

  7 days

• Percent Change in Oxygenation Index (OI) on Days 1-5, and Days 1-7

  7 days

• Percent Change in Dead Space Fraction (Vd/Vt) on Days 1-3, and Days 1-7

  7 days

• Percent Change in Sequential Organ Failure Assessment (SOFA) Score on Days 1-5, and Days 1-7.

  1-5 and 1-7 days

Other Outcomes (6)

• Ventilator-free Days at Day 28

  28 days

• ICU-free Days at Day 28

  28 days

• Hospital-free Days at Day 60

  60 days

Study Arms (2)

Inhaled Carbon Monoxide

EXPERIMENTAL

Inhaled Carbon Monoxide at 200 ppm for up to 90 minutes daily for 3 days.

Drug: Inhaled Carbon Monoxide at 200 ppm

Medical air

PLACEBO COMPARATOR

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

Other: Inhaled Medical air

Interventions

Inhaled Carbon Monoxide at 200 ppm DRUG

Inhaled Carbon Monoxide at 200 ppm for 90 minutes daily for 3 days.

Also known as: iCO

Inhaled Carbon Monoxide

Inhaled Medical air OTHER

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

Medical air

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All intubated patients ≥ 18 years old with ARDS
• 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
• A need for positive pressure ventilation by an endotracheal or tracheal tube
• Respiratory failure not fully explained by cardiac failure or fluid overload; need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present.
• ARDS onset is defined as the time the last of criteria 1-4 are met. ARDS must persist through the enrollment time window of 168 hours.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Age less than 18 years
• Greater than 168 hours since ARDS onset
• Pregnant or breastfeeding
• Prisoner
• Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
• No consent/inability to obtain consent or appropriate legal representative not available
• Physician refusal to allow enrollment in the trial
• Moribund patient not expected to survive 24 hours
• No arterial or central line/no intent to place an arterial or central line
• No intent/unwillingness to follow lung protective ventilation strategy
• Severe hypoxemia defined as SpO2 \< 95 or PaO2 \< 90 on FiO2 ≥ 0.9
• Hemoglobin \< 7.0 g/dL
• Subjects who are Jehovah's Witnesses or are otherwise unable or unwilling to receive blood transfusions during hospitalization
• Acute myocardial infarction (MI) or acute coronary syndrome (ACS) within the last 90 days

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Massachusetts General Hospital: collaborator
• Weill Medical College of Cornell University: collaborator
• Duke University: collaborator
• Durham VA Medical Center: collaborator
• New York Presbyterian Brooklyn Methodist Hospital: collaborator
• Duke Regional Hospital: collaborator
• U.S. Army Medical Research Acquisition Activity: collaborator
• Washington University School of Medicine: collaborator

Study Sites (7)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

New York-Presbyterian Brooklyn Methodist Hospital

Brooklyn, New York, 11215, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Duke Regional Hospital

Durham, North Carolina, 27704, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

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MeSH Terms

Conditions

Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Limitations and Caveats

Due to low enrollment, a limited number of measurements prevents us from estimating measures of variance and dispersion.

Results Point of Contact

• Title: Rebecca Baron MD, Co-PI
• Organization: Brigham and Women's Hospital

rbaron@bwh.harvard.edu

6177326660

Study Officials

• Rebecca Baron, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: The study drug will be blinded to the study staff using identical tanks containing either CO or placebo air. The administering respiratory therapist (RT) and a physician study staff member will be unblinded to the treatment assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: January 10, 2019
• Study Start: September 30, 2019
• Primary Completion: April 13, 2021
• Study Completion: April 13, 2021
• Last Updated: June 16, 2026
• Results First Posted: June 16, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)