NEW ORLEANS — Patients with pulmonary fibrosis who are at risk for pulmonary hypertension experienced improvements in physical activity after treatment with inhaled nitric oxide, according to a study presented at the CHEST Annual Meeting.
In a randomized, double-blind, placebo-controlled study, Steven D. Nathan, MD, FCCP, from the advanced lung disease and lung transplant program at Inova Fairfax Hospital, and colleagues sought to assess the safety and efficacy of pulsed inhaled nitric oxide at 30 µg/kg based on ideal body weight per hour (n = 23), as compared with placebo (n = 18), in patients at risk for pulmonary hypertension associated with pulmonary fibrosis on long-term oxygen therapy.
Patients had a wide range of pulmonary fibrosing interstitial lung diseases, according to Nathan.
Results showed that patients experienced a placebo-corrected 34% improvement in physical activity, as measured by a wrist-worn medical grade actigraph, with inhaled nitric oxide during the 8-week blinded treatment period. Notably, whereas overall physical activity was maintained in the treatment arm, there was a significant decrease in the placebo arm (P = .05).
“What was most interesting and most important was a lot of this decrease was driven by moderate and vigorous physical activity, which is where you see an improvement in the treatment arm and deterioration in the placebo arm after 8 weeks,” Nathan said during a presentation of the data.
The researchers also conducted a responder analysis in which they chose a 15% change, either improvement or decline, as likely clinically significant. Overall, 13% of the treatment arm experienced improvement vs. 0% of the placebo arm. Regarding moderate to vigorous physical activity, 23% of the treatment arm experienced improvement vs. 0% of the placebo arm. Further, more patients who received placebo vs. inhaled nitric oxide experienced a 15% decline in moderate to vigorous physical activity (71% vs. 38%).
After the 8-week blinded treatment period, 18 patients entered the open-label extension study during which they were transitioned to inhaled nitric oxide at a dose of 45 µg/kg based on ideal body weight per hour for at least 8 weeks and then to treatment at a dose of 75 µg/kg based on ideal body weight per hour.
During open-label treatment with inhaled nitric oxide 45 µg/kg based on ideal body weight per hour, the average increase in moderate to vigorous physical activity was 1% per week , including among patients who were on placebo and transitioned from a decline in physical activity during the blinded treatment period. The 10 patients who continued to the higher dose of inhaled nitric oxide also maintained an average increase of 1% per week in moderate to vigorous physical activity.
Inhaled nitric oxide was generally well tolerated, with equivalent rates of adverse events occurring in both the treatment and placebo arms (65.2% and 72.2%, respectively) and only four patients — two in each arm — discontinuing the study.
“This is a sick group of patients obviously, so there were adverse events reported, but none were thought to be attributable to the inhaled nitric oxide,” Nathan said.
Looking ahead, patients in the open-label extension will continue to be monitored and should results be positive, the researchers will enter a pivotal phase 3 study with actigraphy activity monitoring as the primary endpoint, which has been agreed upon by the FDA, according to Nathan.
“Actigraphy and activity monitoring is kind of a step beyond the 6-minute walk test. What we’re interested in is how patients feel and function. They tell us how they feel, and we get a sense of how they might function based on the 6-minute walk test, but what actigraphy gives us is actually how they do function once they leave the clinic. I think this is emerging as a viable and valuable endpoint in clinical trials,” he said. – by Melissa Foster
Nathan SD. Late Breaking Abstracts. Presented at: CHEST Annual Meeting; Oct. 19-23, 2019; New Orleans.
Disclosures: Nathan reports he has received honoraria from Boehringer Ingelheim and consulting fees from Bellerophon, Promedior, Roche-Genentech, and United Therapeutics.