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Background: The interstitial lung diseases include a variety of disorders, many of which are characterized by fibrotic changes (fILD). Of the fILDs, Idiopathic pulmonary fibrosis is the most common. Pulmonary hypertension (PH) frequently complicates fILD and is associated with impaired functional capability, lower physical activity, and significantly reduced life expectancy. There is no proven treatment for patients with fILD-PH. We report results from the first cohort of a phase 2b/3 trial with pulsed inhaled nitric oxide (iNO) in patients with fILD-PH., Methods: Subjects in cohort 1 were randomized to iNO 30 μg/kg ideal body weight/h (iNO30) or placebo for 8 weeks of blinded treatment; subjects then transitioned to open-label extension (OLE) on iNO30 followed by dose escalation to iNO45 then iNO75. Activity monitoring was used to assess changes in daily activity. Safety and efficacy were evaluated., Results: Twenty-three patients were randomized to iNO30 and 18 to placebo. During blinded treatment, iNO30 subjects showed an average improvement in moderate/vigorous physical activity (MVPA) and remained stable in overall activity. Placebo subjects showed an average drop of 26% in MVPA and a 12% drop in overall activity. The iNO group had an improvement in oxygen saturation. During OLE, subjects maintained their activity levels including placebo subjects who transitioned from a decline to a maintenance in all activity parameters. Inhaled nitric oxide at all doses (30, 45, and 75) was safe and well tolerated., Conclusions: Treatment with iNO30 demonstrated clinically and statistically significant benefit in MVPA and clinically significant benefit in overall activity. In the OLE, higher doses of iNO were also safe and well tolerated while showing maintenance in activity parameters., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Rationale: Inhaled nitric oxide (iNO) has been shown to result in benefits in moderate to vigorous physical activity (MVPA) in patients with fibrotic interstitial lung disease (f-ILD) receiving supplemental oxygen in two independent trials. Objective: This phase III randomized, double-blind, placebo-controlled study sought to validate the benefit of ambulatory iNO in patients with f-ILD requiring supplemental oxygen. Methods: Patients with f-ILD receiving supplemental long-term oxygen were randomized in a 1:1 fashion to iNO at 45 μg/kg ideal body weight per hour or placebo for 16 weeks. The primary outcome was the change from baseline to Week 16 in MVPA assessed by accelerometry. Secondary outcomes included overall activity, 6-minute-walk distance and patient-reported outcomes. Results: 145 patients were enrolled; 75 were assigned to receive iNO and 70 placebo. The changes from baseline in MVPA at 16 weeks were −9.2 min/d (standard error, 3.51) in the iNO45 group and −3.7 min/d (3.76) in the placebo group (difference, 5.5; P = 0.265). No statistically significant differences between the two treatment arms were found for any of the secondary outcomes. A subgroup analysis of patients with an intermediate or high probability of pulmonary hypertension on echocardiography did not demonstrate any benefit. The most common adverse events reported were respiratory tract infections, but the therapy was generally very well tolerated. Conclusions: There was no demonstrable benefit to iNO in patients with f-ILD receiving supplemental oxygen in daily physical activity assessed by actigraphy, a potential novel clinical trial endpoint. Clinical trial registered with (NCT 03267108). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The interstitial lung diseases include a variety of disorders, many of which are characterized by fibrotic changes (fILD). Of the fILDs, Idiopathic pulmonary fibrosis is the most common. Pulmonary hypertension (PH) frequently complicates fILD and is associated with impaired functional capability, lower physical activity, and significantly reduced life expectancy. There is no proven treatment for patients with fILD-PH. We report results from the first cohort of a phase 2b/3 trial with pulsed inhaled nitric oxide (iNO) in patients with fILD-PH.Methods: Subjects in cohort 1 were randomized to iNO 30 μg/kg ideal body weight/h (iNO30) or placebo for 8 weeks of blinded treatment; subjects then transitioned to open-label extension (OLE) on iNO30 followed by dose escalation to iNO45 then iNO75. Activity monitoring was used to assess changes in daily activity. Safety and efficacy were evaluated.Results: Twenty-three patients were randomized to iNO30 and 18 to placebo. During blinded treatment, iNO30 subjects showed an average improvement in moderate/vigorous physical activity (MVPA) and remained stable in overall activity. Placebo subjects showed an average drop of 26% in MVPA and a 12% drop in overall activity. The iNO group had an improvement in oxygen saturation. During OLE, subjects maintained their activity levels including placebo subjects who transitioned from a decline to a maintenance in all activity parameters. Inhaled nitric oxide at all doses (30, 45, and 75) was safe and well tolerated.Conclusions: Treatment with iNO30 demonstrated clinically and statistically significant benefit in MVPA and clinically significant benefit in overall activity. In the OLE, higher doses of iNO were also safe and well tolerated while showing maintenance in activity parameters. [ABSTRACT FROM AUTHOR]

(PH-PF) ON LONG TERM OXYGEN THERAPY B PURPOSE: b Pulmonary fibrosis (PF) is made up of a variety of fibrotic lung diseases, the largest of which is IPF (Idiopathic Pulmonary Fibrosis). Inhaled Nitric Oxide (iNO) at a dose of 30 mcg/kg IBW/hr (Cohort 1) has been demonstrated to improve moderate to vigorous physical activity (MVPA) by 34% (placebo-corrected) in an 8-week controlled trial. [Extracted from the article]