Title: A Phase II Clinical Trial of Low-Dose Inhaled Carbon Monoxide in Idiopathic Pulmonary Fibrosis.

Authors: Rosas, Ivan O; Goldberg, Hilary J; Collard, Harold R; El-Chemaly, Souheil; Flaherty, Kevin; Hunninghake, Gary M; Lasky, Joseph A; Lederer, David J; Machado, Roberto; Martinez, Fernando J; Maurer, Rie; Teller, Danielle; Noth, Imre; Peters, Elizabeth; Raghu, Ganesh; Garcia, Joe G N; Choi, Augustine M K

Published In Chest, (2018 01)

Abstract: BACKGROUND: Preclinical studies have demonstrated that low-dose carbon monoxide (CO) can abrogate experimental lung fibrosis. To test the therapeutic role of inhaled CO, we designed a clinical study in patients with idiopathic pulmonary fibrosis (IPF). METHODS: We conducted a multicenter, phase IIa, double-blinded, sham-controlled, clinical trial. Patients with IPF were randomized to treatment with inhaled CO at 100 to 200 parts per million or to inhaled 21% oxygen for 2 h daily, twice weekly, for 12 weeks. The primary study end point was the difference in change in matrix metalloproteinase-7 (MMP7) serum concentration after 12 weeks of treatment. Secondary end points included pulmonary function test measures, 6-min walk distance, rates of adverse events, acute exacerbation, hospitalization and death, and quality of life measures. RESULTS: Fifty-eight subjects were randomized to treatment with inhaled CO (n = 29) or placebo (n = 29). Despite modest increases in CO blood levels, the change in MMP7 concentrations after 12 weeks of treatment did not significantly differ between the study arms (MMP7 difference at week 12, -0.90 ng/mL; 95% CI, -4.18 to 2.38 ng/mL). No differences were observed in physiologic measures, incidence of acute exacerbations, hospitalization, death, or patient-reported outcomes. Importantly, no differences in distribution of adverse events were noted between the treatment arms. CONCLUSIONS: Inhaled CO is well tolerated and can be safely administered to patients with IPF in the ambulatory setting; however, inhaled CO did not result in significant changes in study end points. Our findings support testing the efficacy of inhaled therapies in future IPF clinical trials. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01214187; URL: www.clinicaltrials.gov.

PubMed ID: 29100885

MeSH Terms: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Carbon Monoxide/administration & dosage*; Carbon Monoxide/adverse effects; Carboxyhemoglobin/metabolism; Double-Blind Method; Female; Forced Expiratory Volume/physiology; Humans; Idiopathic Pulmonary Fibrosis/blood; Idiopathic Pulmonary Fibrosis/physiopathology; Idiopathic Pulmonary Fibrosis/therapy*; Male; Middle Aged; Patient Reported Outcome Measures; Treatment Outcome; Vital Capacity/physiology; Young Adult