Status:
ACTIVE_NOT_RECRUITING
Safety Study of Inhaled Carbon Monoxide to Treat Pneumonia and Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS)
Lead Sponsor:
Brigham and Women's Hospital
Collaborating Sponsors:
Weill Medical College of Cornell University
Massachusetts General Hospital
Conditions:
Acute Respiratory Distress Syndrome
Sepsis
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
This study is a multi-center, randomized, partially double-blind, and placebo-controlled Phase Ib clinical trial of inhaled CO (iCO) for the treatment of sepsis-induced acute respiratory distress synd...
Detailed Description
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 manage...
Eligibility Criteria
Inclusion
- All patients (age 18 and older) will be eligible for inclusion if they meet all of the following consensus criteria for sepsis and ARDS3,4 or if they meet the criteria for pneumonia as described below.
- Patients with sepsis are defined as those with life-threatening organ dysfunction caused by a dysregulated host response to infection:
- Suspected or proven infection: Sites of infection include thorax, urinary tract, abdomen, skin, sinuses, central venous catheters, and central nervous system
- Increase in Sequential Organ Failure Assessment (SOFA) Score ≥ 2 over baseline
- 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 is present
- Pneumonia (without ARDS or sepsis) will be defined as a unilateral or bilateral lung infiltrate on chest X-ray or chest CT (not fully explained by effusions, lobar/lung collapse or nodules) in the setting of receiving mechanical ventilation, a new suspected respiratory infection, an increase in SOFA score less than 2 at the time of randomization (baseline).
- Pneumonia (with sepsis, without ARDS) will be defined as a unilateral or bilateral lung infiltrate on chest X-ray or chest CT (not fully explained by effusions, lobar/lung collapse or nodules) in the setting of receiving mechanical ventilation and a new suspected respiratory infection with an increase in SOFA score of ≥ 2 over baseline at the time of randomization. Pneumonia with bilateral opacities, PaO2/FiO2 ratio ≤ 300, or an increase in SOFA score greater than or equal to 2 over baseline will continue to be considered ARDS and sepsis.
Exclusion
- 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 line 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
- Severe cardiopulmonary disease classified as New York Heart Association (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
- Severe airway inhalational injury
- Use of high frequency oscillatory ventilation
- Use of extracorporeal membrane oxygenation (ECMO)
- Use of inhaled pulmonary vasodilator therapy (eg. nitric oxide \[NO\] or prostaglandins)
- Diffuse alveolar hemorrhage from vasculitis
- Concurrent participation in other investigational drug study
Key Trial Info
Start Date :
December 6 2023
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 31 2026
Estimated Enrollment :
5 Patients enrolled
Trial Details
Trial ID
NCT04870125
Start Date
December 6 2023
End Date
March 31 2026
Last Update
December 8 2025
Active Locations (6)
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1
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
2
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
3
Washington University
St Louis, Missouri, United States, 63110
4
New York-Presbyterian Brooklyn Methodist Hospital
Brooklyn, New York, United States, 11215