Safety Study of Inhaled Carbon Monoxide to Treat Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS)

• Status: Not yet recruiting
• Trial end date: 2025-09-01
• Target enrollment: 0
• Participant gender: All

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 syndrome (ARDS). The purpose of this study is to evaluate the safety and accuracy of a Coburn-Forster-Kane (CFK) equation-based personalized iCO dosing algorithm to achieve a target carboxyhemoglobin (COHb) level of 6-8% in patients with sepsis-induced ARDS. We will also examine the biologic readouts of low dose iCO therapy in patients with sepsis-induced ARDS.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brigham and Women's Hospital
• Collaborators: Duke University; Massachusetts General Hospital; National Heart, Lung, and Blood Institute (NHLBI); Weill Medical College of Cornell University
• Treatments: Carbon Monoxide

Criteria

Inclusion Criteria:

All patients (age 18 and older) will be eligible for inclusion if they meet all of the following consensus criteria for sepsis and ARDS.

Patients with sepsis are defined as those with life-threatening organ dysfunction caused by a dysregulated host response to infection:

1. Suspected or proven infection: Sites of infection include thorax, urinary tract, abdomen, skin, sinuses, central venous catheters, and central nervous system

2. Increase in Sequential Organ Failure Assessment (SOFA) Score ≥ 2 over baseline

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 is present

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 line 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. Severe cardiopulmonary disease classified as New York Heart Association (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

20. Severe airway inhalational injury

21. Use of high frequency oscillatory ventilation

22. Use of extracorporeal membrane oxygenation (ECMO)

23. 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