Acute Respiratory Distress SyndromePhase 2NCT03799874
Safety and Efficacy Study of Inhaled Carbon Monoxide to Treat Acute Respiratory Distress Syndrome (ARDS)
A Phase 2 study testing Inhaled Carbon Monoxide at 200 ppm and Inhaled Medical air in people with Acute Respiratory Distress Syndrome, run by Brigham and Women's Hospital at 7 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- What is being tested?
- Inhaled Carbon Monoxide at 200 ppm and Inhaled Medical air
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 7 sitesUnited States
- Study dates
- 30 Sep 2019to 13 Apr 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 26Show fewer
- 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
- Coronary artery bypass graft (CABG) surgery within 30 days
- Angina pectoris or use of nitrates with activities of daily living
- Cardiopulmonary disease classified as NYHA class IV
- Stroke (ischemic or hemorrhagic) within the prior 1 month, cardiac arrest requiring CPR within the prior 72 hours, or inability to assess mental status following cardiac arrest
- Burns > 40% total body surface area (TBSA)
- Severe airway inhalational injury
- Use of high frequency oscillatory ventilation
- Use of extracorporeal membrane oxygenation (ECMO)
- Concomitant use of inhaled pulmonary vasodilator therapy (eg. nitric oxide [NO] or prostaglandins)
- Diffuse alveolar hemorrhage from vasculitis
- Concurrent participation in other investigational drug study
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
New York-Presbyterian Brooklyn Methodist Hospital
Brooklyn, New York, 11215
Duke Regional Hospital
Durham, North Carolina, 27704
Duke University Hospital
Durham, North Carolina, 27710
Weill Cornell Medical College
New York, New York, 10065
Washington University
St Louis, Missouri, 63130
About this study
Official title: A Phase II Trial of Inhaled Carbon Monoxide for the Treatment of Acute Respiratory Distress Syndrome (ARDS)
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
Read the detailed description
Acute respiratory distress syndrome (ARDS) is a devastating disease affecting military, veteran, and civilian populations. ARDS is a syndrome of severe acute lung inflammation and hypoxemic respiratory failure with an incidence of 180,000 cases annually in the United States. Despite recent advances in critical care management and lung protective ventilation strategies, ARDS morbidity and mortality remain unacceptably high. The lack of specific effective therapies for ARDS indicates a need for new treatments that target novel pathways. Carbon monoxide (CO) represents a novel therapeutic modality in ARDS based on data obtained in experimental models of ARDS over the past decade.
CO has been shown to be protective in experimental models of acute lung injury (ALI) and sepsis. Furthermore, multiple human studies have demonstrated that experimental administration of several different concentrations of CO is well tolerated and that low dose inhaled CO can be safely administered to subjects in a controlled research environment. The investigators have previously conducted a Phase I trial of low dose iCO in ARDS which demonstrated that precise administration of low dose iCO (100 and 200 ppm) is feasible, well-tolerated, and safe in patients with sepsis-induced ARDS.
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.
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- Inhaled Carbon Monoxide at 200 ppm, Inhaled Medical air
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhaled Carbon Monoxide at 200 ppmDrug
Also called iCO
Inhaled Carbon Monoxide at 200 ppm for 90 minutes daily for 3 days.
Inhaled Medical airOther
Inhaled Medical Air for up to 90 minutes daily for 3 days.
| Study group | Role | What they receive |
|---|---|---|
| Inhaled Carbon Monoxide | Experimental | Inhaled Carbon Monoxide at 200 ppm for up to 90 minutes daily for 3 days. Receives: Drug: Inhaled Carbon Monoxide at 200 ppm |
| Medical air | Placebo comparator | Inhaled Medical Air for up to 90 minutes daily for 3 days. Receives: Other: Inhaled Medical air |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
- Acute MI within 48 hours of study drug administration
- Acute cerebrovascular accident (CVA) within 48 hours of study drug administration
- New onset atrial or ventricular arrhythmia requiring DC cardioversion within 48 hours of study drug administration
- 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
- Increase in COHb ≥ 10%
- Increase in lactate by ≥ 2 mmol/L within 6 hours of study drug administration
Measured: 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.
Measured: 5 days
Secondary outcomes (7)
Lung Injury Score (LIS) on Days 1-5, and on Days 1-7
The Lung Injury Score (LIS) is a composite 4-point scoring system including the PaO2/FiO2, PEEP, quasi-static respiratory compliance, and the extent of infiltrates on the chest X-ray. Each of the four components is categorized from 0 to 4, where a higher number is worse. The total Lung Injury Score is obtained by dividing the aggregate sum by the number of components used. Previous randomized clinical trials in ARDS have shown that a decreased LIS correlates with improvement in lung physiology as well as important clinical outcomes including mortality and ventilator-free days (VFDs). The number presented is the average difference from beginning to end of treatment. The limited number of measurements prevent the variance and measures of dispersion calculations; therefore we present the average of data from the available subjects in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
Measured: 7 days
Percent Change in PaO2/FiO2 Ratio on Days 1-5, and on Days 1-7
PaO2/FiO2 will be measured daily on days 1-5 and days 1-7 in ventilated subjects. The limited number of measurements prevent the variance and measures of dispersion calculations; therefore we present the average of data from the available subjects in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
Measured: 7 days
Percent Change in Oxygenation Index (OI) on Days 1-5, and Days 1-7
The oxygenation index will be measured on days 1-5 and on days 1-7 in ventilated subjects. Oxygenation index is calculated as (FiO2 X mean airway pressure)/PaO2. We provide change in Oi from baseline. Oi is only measured when subjects are ventilated, therefore not all timepoints are available. The limited number of measurements prevent the variance and measures of dispersion calculations; therefore we present the average of data from the available subjects in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
Measured: 7 days
Percent Change in Dead Space Fraction (Vd/Vt) on Days 1-3, and Days 1-7
The dead space fraction will be measured days 1-3 and days 1-7 in ventilated subjects. We present change in dead space fraction between initial and final measurements that were available (measurements only taken while the subjects were intubated). The limited number of measurements prevent the variance and measures of dispersion calculations; therefore we present the average of data from the available subjects in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
Measured: 7 days
Percent Change in Sequential Organ Failure Assessment (SOFA) Score on Days 1-5, and Days 1-7.
Organ failure will be assessed using the SOFA score. SOFA scores will be assessed daily on days 1-5 and day 7, as the SOFA score has been shown to be a reliable prognostic indicator of outcomes in critically ill patients. To calculate the Sequential Organ Failure Assessment (SOFA) score, each of the six components (Respiratory, Coagulation, Liver, Cardiovascular, Central Nervous System, Renal) is categorized from 0-4, where a higher number is worse. The SOFA score (0-24) will be calculated by summing all six components. We present changes in SOFA score over the time of hospitalization, over the time of ICU admission (up to days 5 and 7 for the enrolled subjects). The limited number of measurements prevent the variance and measures of dispersion calculations; therefore we present the average of data from the available subjects in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
Measured: 1-5 and 1-7 days
Absolute Value of Biomarkers of Inflammation and Inflammasome Activation
Cytokine plasma levels (eg. IL-1B) will be measured by ELISA daily on days 1-3 and on day 4. We report the absolute Mean Fluorescent Intensity (MFI) of each sample at pretreatment time point of day 4. Limited number of measurements prevents variance and measures of dispersion analyses; therefore we present the data from the subjects available in each group and report as "Number" without standard deviation, since measures of dispersion cannot be calculated.
Measured: 4 days
Percent Change in Lipid Mediators
Lipid mediators (LM) and specialized pro-resolving mediators (SPMs) will be measured in plasma using liquid chromatography-tandem mass spectrometry (LC-MS-MS) based methods daily on days 1-3 and on day 4. The percentage change from baseline at day 1 to post treatment at day 4 is reported. A representative LM is shown (14-HDHA (14-hydroxy-4Z,7Z,10Z,12E,16Z,19Z-docosahexaenoic acid) is an oxidized metabolite of omega-3 docosahexaenoic acid (DHA)). Limited number of measurements prevents variance and measures of dispersion analyses; therefore we present the data from the subjects available in each group and report as "Number" without standard deviation, since measures of dispersion cannot be calculated.
Measured: 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2019
- Study start30 Sep 2019
- Primary completion13 Apr 2021
- Study completion13 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital, Weill Medical College of Cornell University, Duke University, Durham VA Medical Center, New York Presbyterian Brooklyn Methodist Hospital, Duke Regional Hospital, U.S. Army Medical Research Acquisition Activity, Washington University School of Medicine
- Responsible party
- Principal investigator, Rebecca Baron, Brigham and Women's Hospital
- Investigators
- Rebecca Baron, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03799874
- Sponsor's protocol ID
- 2018P002051
- Other IDs
- CDMRP-PR171025, W81XWH1810667
- Status last verified
- May 2026
- First submitted
- 6 Dec 2018
- Last updated
- 16 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nakahira K, Kyung SY, Rogers AJ, Gazourian L, Youn S, Massaro AF, Quintana C, Osorio JC, Wang Z, Zhao Y, Lawler LA, Christie JD, Meyer NJ, Mc Causland FR, Waikar SS, Waxman AB, Chung RT, Bueno R, Rosas IO, Fredenburgh LE, Baron RM, Christiani DC, Hunninghake GM, Choi AM. Circulating mitochondrial DNA in patients in the ICU as a marker of mortality: derivation and validation. PLoS Med. 2013 Dec;10(12):e1001577; discussion e1001577. doi: 10.1371/journal.pmed.1001577. Epub 2013 Dec 31.
PubMed 24391478Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, Davies NA, Cooper CE, Singer M. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 2002 Jul 20;360(9328):219-23. doi: 10.1016/S0140-6736(02)09459-X.
PubMed 12133657Jung SS, Moon JS, Xu JF, Ifedigbo E, Ryter SW, Choi AM, Nakahira K. Carbon monoxide negatively regulates NLRP3 inflammasome activation in macrophages. Am J Physiol Lung Cell Mol Physiol. 2015 May 15;308(10):L1058-67. doi: 10.1152/ajplung.00400.2014. Epub 2015 Mar 13.
PubMed 25770182Rhodes MA, Carraway MS, Piantadosi CA, Reynolds CM, Cherry AD, Wester TE, Natoli MJ, Massey EW, Moon RE, Suliman HB. Carbon monoxide, skeletal muscle oxidative stress, and mitochondrial biogenesis in humans. Am J Physiol Heart Circ Physiol. 2009 Jul;297(1):H392-9. doi: 10.1152/ajpheart.00164.2009. Epub 2009 May 22.
PubMed 19465554Fredenburgh LE, Kraft BD, Hess DR, Harris RS, Wolf MA, Suliman HB, Roggli VL, Davies JD, Winkler T, Stenzler A, Baron RM, Thompson BT, Choi AM, Welty-Wolf KE, Piantadosi CA. Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia. Am J Physiol Lung Cell Mol Physiol. 2015 Oct 15;309(8):L834-46. doi: 10.1152/ajplung.00240.2015. Epub 2015 Aug 28.
PubMed 26320156Hausberg M, Somers VK. Neural circulatory responses to carbon monoxide in healthy humans. Hypertension. 1997 May;29(5):1114-8. doi: 10.1161/01.hyp.29.5.1114.
PubMed 9149675Mayr FB, Spiel A, Leitner J, Marsik C, Germann P, Ullrich R, Wagner O, Jilma B. Effects of carbon monoxide inhalation during experimental endotoxemia in humans. Am J Respir Crit Care Med. 2005 Feb 15;171(4):354-60. doi: 10.1164/rccm.200404-446OC. Epub 2004 Nov 19.
PubMed 15557136Peterson JE, Stewart RD. Predicting the carboxyhemoglobin levels resulting from carbon monoxide exposures. J Appl Physiol. 1975 Oct;39(4):633-8. doi: 10.1152/jappl.1975.39.4.633.
PubMed 1194155Stewart RD, Peterson JE, Baretta ED, Bachand RT, Hosko MJ, Herrmann AA. Experimental human exposure to carbon monoxide. Arch Environ Health. 1970 Aug;21(2):154-64. doi: 10.1080/00039896.1970.10667214. No abstract available.
PubMed 5430001Zevin S, Saunders S, Gourlay SG, Jacob P, Benowitz NL. Cardiovascular effects of carbon monoxide and cigarette smoking. J Am Coll Cardiol. 2001 Nov 15;38(6):1633-8. doi: 10.1016/s0735-1097(01)01616-3.
PubMed 11704374Ren X, Dorrington KL, Robbins PA. Respiratory control in humans after 8 h of lowered arterial PO2, hemodilution, or carboxyhemoglobinemia. J Appl Physiol (1985). 2001 Apr;90(4):1189-95. doi: 10.1152/jappl.2001.90.4.1189.
PubMed 11247913Pecorella SR, Potter JV, Cherry AD, Peacher DF, Welty-Wolf KE, Moon RE, Piantadosi CA, Suliman HB. The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle. Am J Physiol Lung Cell Mol Physiol. 2015 Oct 15;309(8):L857-71. doi: 10.1152/ajplung.00104.2015. Epub 2015 Jul 17.
PubMed 26186946Fredenburgh LE, Perrella MA, Barragan-Bradford D, Hess DR, Peters E, Welty-Wolf KE, Kraft BD, Harris RS, Maurer R, Nakahira K, Oromendia C, Davies JD, Higuera A, Schiffer KT, Englert JA, Dieffenbach PB, Berlin DA, Lagambina S, Bouthot M, Sullivan AI, Nuccio PF, Kone MT, Malik MJ, Porras MAP, Finkelsztein E, Winkler T, Hurwitz S, Serhan CN, Piantadosi CA, Baron RM, Thompson BT, Choi AM. A phase I trial of low-dose inhaled carbon monoxide in sepsis-induced ARDS. JCI Insight. 2018 Dec 6;3(23):e124039. doi: 10.1172/jci.insight.124039.
PubMed 30518685Rosas IO, Goldberg HJ, Collard HR, El-Chemaly S, Flaherty K, Hunninghake GM, Lasky JA, Lederer DJ, Machado R, Martinez FJ, Maurer R, Teller D, Noth I, Peters E, Raghu G, Garcia JGN, Choi AMK. A Phase II Clinical Trial of Low-Dose Inhaled Carbon Monoxide in Idiopathic Pulmonary Fibrosis. Chest. 2018 Jan;153(1):94-104. doi: 10.1016/j.chest.2017.09.052. Epub 2017 Oct 31.
PubMed 29100885
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Inhaled Carbon Monoxide for the Treatment of Acute Respiratory Distress Syndrome (ARDS)
- ClinicalTrials.gov ID
- NCT03799874
- Acronym / sponsor ID
- 2018P002051
- Conditions
- Acute Respiratory Distress Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital, Weill Medical College of Cornell University, Duke University, Durham VA Medical Center, New York Presbyterian Brooklyn Methodist Hospital, Duke Regional Hospital, U.S. Army Medical Research Acquisition Activity, Washington University School of Medicine
- Study start
- 30 Sep 2019 (actual)
- Primary completion
- 13 Apr 2021 (actual)
- Study completion
- 13 Apr 2021 (actual)
- First posted
- 10 Jan 2019 (actual)
- Results
- Posted 16 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Acute respiratory distress syndrome (ARDS) is a devastating disease affecting military, veteran, and civilian populations. ARDS is a syndrome of severe acute lung inflammation and hypoxemic respiratory failure with an incidence of 180,000 cases annually in the United States. Despite recent advances in critical care management and lung protective ventilation strategies, ARDS morbidity and mortality remain unacceptably high. The lack of specific effective therapies for ARDS indicates a need for new treatments that target novel pathways. Carbon monoxide (CO) represents a novel therapeutic modality in ARDS based on data obtained in experimental models of ARDS over the past decade.
CO has been shown to be protective in experimental models of acute lung injury (ALI) and sepsis. Furthermore, multiple human studies have demonstrated that experimental administration of several different concentrations of CO is well tolerated and that low dose inhaled CO can be safely administered to subjects in a controlled research environment. The investigators have previously conducted a Phase I trial of low dose iCO in ARDS which demonstrated that precise administration of low dose iCO (100 and 200 ppm) is feasible, well-tolerated, and safe in patients with sepsis-induced ARDS.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inhaled Carbon Monoxide | Experimental | Drug: Inhaled Carbon Monoxide at 200 ppmInhaled Carbon Monoxide at 200 ppm for up to 90 minutes daily for 3 days. |
| Medical air | Placebo comparator | Other: Inhaled Medical airInhaled Medical Air for up to 90 minutes daily for 3 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- All intubated patients ≥ 18 years old with ARDS
- ARDS is defined when all four of the following criteria are met:
- 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.
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inhaled Carbon Monoxide at 200 ppmAlso: iCOInhaled Carbon Monoxide at 200 ppm for 90 minutes daily for 3 days. | Drug | Inhaled Carbon Monoxide |
| Inhaled Medical airInhaled Medical Air for up to 90 minutes daily for 3 days. | Other | Medical air |
Primary outcome
Primary Safety Outcome: Number of Pre-specified Administration-related Adverse Events.
Time frame: 7 days
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
Primary Efficacy Outcome: Change in Mitochondrial DNA (mtDNA) Level From Day 1 to Day 5
Time frame: 5 days
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.
7 secondary outcomes
Lung Injury Score (LIS) on Days 1-5, and on Days 1-7
Time frame: 7 days
Percent Change in PaO2/FiO2 Ratio on Days 1-5, and on Days 1-7
Time frame: 7 days
Percent Change in Oxygenation Index (OI) on Days 1-5, and Days 1-7
Time frame: 7 days
Percent Change in Dead Space Fraction (Vd/Vt) on Days 1-3, and Days 1-7
Time frame: 7 days
Percent Change in Sequential Organ Failure Assessment (SOFA) Score on Days 1-5, and Days 1-7.
Time frame: 1-5 and 1-7 days
Absolute Value of Biomarkers of Inflammation and Inflammasome Activation
Time frame: 4 days
Percent Change in Lipid Mediators
Time frame: 4 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24391478Nakahira K, Kyung SY, Rogers AJ, Gazourian L, Youn S, Massaro AF, Quintana C, Osorio JC, Wang Z, Zhao Y, Lawler LA, Christie JD, Meyer NJ, Mc Causland FR, Waikar SS, Waxman AB, Chung RT, Bueno R, Rosas IO, Fredenburgh LE, Baron RM, Christiani DC, Hunninghake GM, Choi AM. Circulating mitochondrial DNA in patients in the ICU as a marker of mortality: derivation and validation. PLoS Med. 2013 Dec;10(12):e1001577; discussion e1001577. doi: 10.1371/journal.pmed.1001577. Epub 2013 Dec 31.
- Background: PubMed 12133657Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, Davies NA, Cooper CE, Singer M. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 2002 Jul 20;360(9328):219-23. doi: 10.1016/S0140-6736(02)09459-X.
- Background: PubMed 25770182Jung SS, Moon JS, Xu JF, Ifedigbo E, Ryter SW, Choi AM, Nakahira K. Carbon monoxide negatively regulates NLRP3 inflammasome activation in macrophages. Am J Physiol Lung Cell Mol Physiol. 2015 May 15;308(10):L1058-67. doi: 10.1152/ajplung.00400.2014. Epub 2015 Mar 13.
- Background: PubMed 19465554Rhodes MA, Carraway MS, Piantadosi CA, Reynolds CM, Cherry AD, Wester TE, Natoli MJ, Massey EW, Moon RE, Suliman HB. Carbon monoxide, skeletal muscle oxidative stress, and mitochondrial biogenesis in humans. Am J Physiol Heart Circ Physiol. 2009 Jul;297(1):H392-9. doi: 10.1152/ajpheart.00164.2009. Epub 2009 May 22.
- Background: PubMed 26320156Fredenburgh LE, Kraft BD, Hess DR, Harris RS, Wolf MA, Suliman HB, Roggli VL, Davies JD, Winkler T, Stenzler A, Baron RM, Thompson BT, Choi AM, Welty-Wolf KE, Piantadosi CA. Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia. Am J Physiol Lung Cell Mol Physiol. 2015 Oct 15;309(8):L834-46. doi: 10.1152/ajplung.00240.2015. Epub 2015 Aug 28.
- Background: PubMed 9149675Hausberg M, Somers VK. Neural circulatory responses to carbon monoxide in healthy humans. Hypertension. 1997 May;29(5):1114-8. doi: 10.1161/01.hyp.29.5.1114.
- Background: PubMed 15557136Mayr FB, Spiel A, Leitner J, Marsik C, Germann P, Ullrich R, Wagner O, Jilma B. Effects of carbon monoxide inhalation during experimental endotoxemia in humans. Am J Respir Crit Care Med. 2005 Feb 15;171(4):354-60. doi: 10.1164/rccm.200404-446OC. Epub 2004 Nov 19.
- Background: PubMed 1194155Peterson JE, Stewart RD. Predicting the carboxyhemoglobin levels resulting from carbon monoxide exposures. J Appl Physiol. 1975 Oct;39(4):633-8. doi: 10.1152/jappl.1975.39.4.633.
- Background: PubMed 5430001Stewart RD, Peterson JE, Baretta ED, Bachand RT, Hosko MJ, Herrmann AA. Experimental human exposure to carbon monoxide. Arch Environ Health. 1970 Aug;21(2):154-64. doi: 10.1080/00039896.1970.10667214. No abstract available.
- Background: PubMed 11704374Zevin S, Saunders S, Gourlay SG, Jacob P, Benowitz NL. Cardiovascular effects of carbon monoxide and cigarette smoking. J Am Coll Cardiol. 2001 Nov 15;38(6):1633-8. doi: 10.1016/s0735-1097(01)01616-3.
- Background: PubMed 11247913Ren X, Dorrington KL, Robbins PA. Respiratory control in humans after 8 h of lowered arterial PO2, hemodilution, or carboxyhemoglobinemia. J Appl Physiol (1985). 2001 Apr;90(4):1189-95. doi: 10.1152/jappl.2001.90.4.1189.
- Background: PubMed 26186946Pecorella SR, Potter JV, Cherry AD, Peacher DF, Welty-Wolf KE, Moon RE, Piantadosi CA, Suliman HB. The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle. Am J Physiol Lung Cell Mol Physiol. 2015 Oct 15;309(8):L857-71. doi: 10.1152/ajplung.00104.2015. Epub 2015 Jul 17.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rebecca Baron, MD principal investigator
Brigham and Women's Hospital
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Inhaled Carbon Monoxide at 200 ppm and Inhaled Medical air in people with Acute Respiratory Distress Syndrome, run by Brigham and Women's Hospital at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Safety Outcome: Number of Pre-specified Administration-related Adverse Events. (time frame: 7 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03799874, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2026.