Purpose

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 5 tertiary care medical centers including Weill Cornell Medicine/NewYork-Presbyterian Hospital, Brigham and Women's Hospital (BWH), Massachusetts General Hospital (MGH), Duke University Hospital, and the Durham Veterans Administration Medical Center. 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

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

All intubated patients ≥ 18 years old with ARDS 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

An individual who meets any of the following criteria will be excluded from participation in this study: 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 < 80 on FiO2 ≥ 0.8 12. Hemoglobin < 7.5 g/dL or hemoglobin < 8 g/dL and actively bleeding 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) or anoxic/hypoxic brain injury or traumatic brain injury (TBI) within the prior 3 months 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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Care Provider)
Masking Description
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.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Inhaled Carbon Monoxide
Inhaled Carbon Monoxide at 200 ppm for up to 90 minutes daily for 5 days.
  • Drug: Inhaled Carbon Monoxide at 200 ppm
    Inhaled Carbon Monoxide at 200 ppm for 90 minutes daily for 5 days.
    Other names:
    • iCO
Placebo Comparator
Medical air
Inhaled Medical Air for up to 90 minutes daily for 5 days.
  • Other: Inhaled Medical air
    Inhaled Medical Air for up to 90 minutes daily for 5 days.

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Marcos Vidal Melo, MD

More Details

Status
Recruiting
Sponsor
Brigham and Women's Hospital

Study Contact

Laura E Fredenburgh, MD
617-525-9563
lfredenburgh@bwh.harvard.edu

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.