Rationale: Patients with fibrotic
interstitial lung disease often progress to the point of requiring supplemental
oxygen. This is invariably accompanied by an impaired quality of life and limitations on
activities of daily living. Objectives: This study aimed to assess the improvement in physical activity in patients with
interstitial lung disease requiring supplemental
oxygen treated with pulsed inhaled
nitric oxide via INOpulse (Bellerophon
Therapeutics). In addition, it sought to explore the safety and clinical benefits of INOpulse on multiple patient-reported outcomes. Methods: Ambulatory patients with fibrotic
lung disease on supplemental
oxygen were randomized in a 2:1 ratio to inhaled
nitric oxide at 45 μg/kg ideal body weight/h (iNO45) or placebo for 4 months (3 months after baseline) of blinded treatment. The study assessed multiple exploratory efficacy endpoints, including moderate to vigorous physical activity as measured by actigraphy and patient-reported outcomes using the University of California San Diego
shortness of breath questionnaire and the St. George's Respiratory Questionnaire (SGRQ). Results: A total of 44 patients (30 iNO45 and 14 placebo) were enrolled. A placebo-corrected clinical benefit of 12.3 min/d increase in MVPA was observed in the iNO45 group. Clinically meaningful beneficial trends were observed for the University of California San Diego
shortness of breath questionnaire (6.05 points) and the SGRQ total (3.75) scores, as well as the SGRQ activity (5.84), and SGRQ impact (6.30) domains. Conclusions: INOpulse was well tolerated and associated with maintenance of physical activity and improved symptomatology in patients with
interstitial lung disease who require supplemental
oxygen. Further validation of this beneficial effect warrants further study in a phase-3 trial that is currently underway.