NEW ORLEANS – In patients with interstitial lung diseases at risk of pulmonary hypertension, inhaled nitric oxide produced meaningful improvements in activity that have been maintained over the long term, an investigator reported here.
Inhaled nitric oxide, which improved moderate to vigorous physical activity by 34% versus placebo in an 8-week controlled trial, has demonstrated long-term maintenance of activity parameters in open-label extension data, presented at the annual meeting of the American College of Chest Physicians.
The treatment was safe and well tolerated in this cohort of subjects at risk of pulmonary hypertension associated with pulmonary fibrosis (PH-PF), said, director of the advanced lung disease and lung transplant program at Inova Fairfax (Va.) Hospital.
The findings to date suggest inhaled nitric oxide (iNO) is a potentially effective treatment option for patients at risk for pulmonary hypertension, which is associated with poor outcomes in various forms of interstitial lung disease, Dr. Nathan said in his presentation, adding that a second cohort of PH-PF patients has been fully recruited and continue to be followed.
“Hopefully, once we show that iNO is positive and validate what we’ve seen with cohort one, then we’ll be moving on to cohort three, which will be a pivotal phase 3 clinical study with actigraphy activity–monitoring being the primary endpoint, and that has been agreed upon by the Food and Drug Administration,” he said.
The actigraph device used in the study, worn on the wrist of the nondominant arm, continuously measures patient movement in acceleration units and allows for categorization of intensity, from sedentary to vigorous, Dr. Nathan explained in this presentation.
“To me, actigraphy activity–monitoring is kind of a step beyond the 6-minute walk test,” he said. “We get a sense of how [patients] 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. So I think this is emerging as a very viable and valuable endpoint in clinical trials.”
Dr. Nathan reported on 23 patients with a variety of pulmonary fibrotic interstitial lung diseases randomized to receive iNO 30 mcg/kg based on their ideal body weight (IBW) per hour, and 18 who were randomized to placebo, for 8 weeks of blinded treatment. After that, patients from both arms transitioned to open-label treatment, stepping up to 45 mcg/kg IBW/hr for at least 8 weeks, and then to 75 mcg/kg IBW/hr.
After the 8 weeks of blinded treatment, activity as measured by actigraphy was maintained in the patients receiving iNO, and decreased in the placebo arm (P = .05), according to Dr. Nathan, who added that this difference was largely driven by changes in levels of moderate to vigorous physical activity, which improved in the treatment arm, while declining substantially in the placebo arm.
Clinically significant improvements in moderate to vigorous physical activity were seen in 23.1% of patients in the treatment arm and 0% of the placebo arm, while clinically significant declines in that measure were seen in 38.5% of the treatment group versus 71.4% of the placebo group.
Data from the open-label extension phase, which included a total of 18 patients, show that activity was “well maintained” over a total of 20 weeks, with patients formerly in the placebo arm demonstrating levels of activity comparable to what was achieved in the patients randomized to treatment: “We felt like this supports the clinical efficacy of the nitric oxide effect, that the placebo arm started to behave like the treatment arm,” Dr. Nathan said.
Some adverse events were reported in the study, but none were felt to be attributable to the iNO, according to Dr. Nathan.
Dr. Nathan provided disclosures related to Roche-Genentech, Boehringer Ingelheim, Promedior, Bellerophon, and United Therapeutics.
SOURCE: Nathan SD et al. CHEST 2019. .