Safety and Efficacy Study of Inhaled Carbon Monoxide to Treat Acute Respiratory Distress Syndrome (ARDS)
NCT ID: NCT03799874
Last Updated: 2025-08-24
Study Results
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Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2
32 participants
INTERVENTIONAL
2019-07-01
2026-01-31
Brief Summary
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Detailed Description
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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
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Inhaled Carbon Monoxide
Inhaled Carbon Monoxide at 200 ppm for up to 90 minutes daily for 3 days.
Inhaled Carbon Monoxide at 200 ppm
Inhaled Carbon Monoxide at 200 ppm for 90 minutes daily for 3 days.
Medical air
Inhaled Medical Air for up to 90 minutes daily for 3 days.
Inhaled Medical air
Inhaled Medical Air for up to 90 minutes daily for 3 days.
Interventions
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Inhaled Carbon Monoxide at 200 ppm
Inhaled Carbon Monoxide at 200 ppm for 90 minutes daily for 3 days.
Inhaled Medical air
Inhaled Medical Air for up to 90 minutes daily for 3 days.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
1. ARDS is defined when all four of the following criteria are met:
1. A PaO2/FiO2 ratio ≤ 300 with at least 5 cm H2O positive end-expiratory airway pressure (PEEP)
2. 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
3. A need for positive pressure ventilation by an endotracheal or tracheal tube
4. 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.
2. 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.
Exclusion Criteria
1. Age less than 18 years
2. Greater than 168 hours since ARDS onset
3. Pregnant or breastfeeding
4. Prisoner
5. 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)
6. No consent/inability to obtain consent or appropriate legal representative not available
7. Physician refusal to allow enrollment in the trial
8. Moribund patient not expected to survive 24 hours
9. No arterial or central line/no intent to place an arterial or central line
10. No intent/unwillingness to follow lung protective ventilation strategy
11. Severe hypoxemia defined as SpO2 \< 95 or PaO2 \< 90 on FiO2 ≥ 0.9
12. Hemoglobin \< 7.0 g/dL
13. Subjects who are Jehovah's Witnesses or are otherwise unable or unwilling to receive blood transfusions during hospitalization
14. Acute myocardial infarction (MI) or acute coronary syndrome (ACS) within the last 90 days
15. Coronary artery bypass graft (CABG) surgery within 30 days
16. Angina pectoris or use of nitrates with activities of daily living
17. Cardiopulmonary disease classified as NYHA class IV
18. 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
19. Burns \> 40% total body surface area (TBSA)
20. Severe airway inhalational injury
21. Use of high frequency oscillatory ventilation
22. Use of extracorporeal membrane oxygenation (ECMO)
23. Concomitant use of inhaled pulmonary vasodilator therapy (eg. nitric oxide \[NO\] or prostaglandins)
24. Diffuse alveolar hemorrhage from vasculitis
25. Concurrent participation in other investigational drug study
18 Years
ALL
No
Sponsors
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Massachusetts General Hospital
OTHER
Weill Medical College of Cornell University
OTHER
Duke University
OTHER
Durham VA Medical Center
FED
New York Presbyterian Brooklyn Methodist Hospital
OTHER
Duke Regional Hospital
OTHER
U.S. Army Medical Research Acquisition Activity
FED
Washington University School of Medicine
OTHER
Brigham and Women's Hospital
OTHER
Responsible Party
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Rebecca Baron
Associate Professor of Medicine
Principal Investigators
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Rebecca Baron, MD
Role: PRINCIPAL_INVESTIGATOR
Brigham and Women's Hospital
Locations
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Massachusetts General Hospital
Boston, Massachusetts, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
Washington University
St Louis, Missouri, United States
New York-Presbyterian Brooklyn Methodist Hospital
Brooklyn, New York, United States
Weill Cornell Medical College
New York, New York, United States
Duke Regional Hospital
Durham, North Carolina, United States
Duke University Hospital
Durham, North Carolina, United States
Countries
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References
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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.
Brealey 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.
Jung 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.
Rhodes 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.
Fredenburgh 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.
Hausberg 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.
Mayr 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.
Peterson 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.
Stewart 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.
Zevin 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.
Ren 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.
Pecorella 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.
Fredenburgh 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.
Rosas 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.
Other Identifiers
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CDMRP-PR171025, W81XWH1810667
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
2018P002051
Identifier Type: -
Identifier Source: org_study_id
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