Inhaled Nitric Oxide at Higher Dose Improves Activity in PH Associated With ILD

After careful consideration, the American Thoracic Society canceled its annual meeting that was to take place in Philadelphia, Pennsylvania from May 15-20, because of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Although the live events will not proceed as planned, our readers can still find coverage of research that was scheduled to be presented at the meeting. A virtual event is being planned for later this year.

Inhaled nitric oxide 45 mcg/kg of ideal body weight per hour (iNO45) was safe, well tolerated, and effective for improving moderate to vigorous physical activity (MVPA) in patients at risk for pulmonary hypertension (PH) associated with fibrotic interstitial lung disease (ILD) who were on long-term oxygen therapy, according to the results of a placebo-controlled study intended to be presented at the American Thoracic Society (ATS) International Conference,. (Select research is slated to be presented in a virtual format later this year.)

The study included patients on supplemental oxygen therapy who were considered at low and intermediate or high risk of PH-fibrotic ILD. Patients were randomly assigned to either iNO45 (n=30) or placebo (n=14) for a 16-week blinded treatment period. The primary end point was MVPA, which was assessed by measures of activities of daily living (ADL).

Changes in activity levels were assessed at 4 months and compared with baseline. Activity levels were measured with a wrist-worn medical grade activity monitor. Patient-reported outcomes (PROs) using the St. George’s Respiratory Questionnaire (SGRQ) and University of California, San Diego Shortness of Breath Questionnaire (UCSD SOBQ) were included as secondary end points. These end points were considered clinically important if there were a 5-point change in the UCSD SOBQ and a 4-point change in the SGRQ domains.

Treatment with iNO45 resulted in a statistically significant clinical benefit compared with placebo in terms of MVPA (+14 min/d; P =.02). Activity levels deteriorated throughout the study in patients who were randomly assigned to placebo, whereas activity levels remained stable in patients randomly assigned to active therapy. The investigators observed a 7% benefit in overall activity with iNO45 vs placebo.

Significant changes of 4.8 points in the UCSD SOBQ, 3.3 points in the SGRQ Total, 4.8 points in the Activity domain, and 5.7 points in the Impact domain scores were also observed with iNO45. The percentage of patients who experienced serious adverse events was lower in the group that received iNO45 vs placebo (10% vs 21%). There were no reported deaths during the study period.

The researchers concluded that another phase 3 study, the iNOpulse, is currently planned to further evaluate inhaled nitric oxide in patients with fibrotic ILD.

Reference

Nathan SD, Flaherty KR, Glassberg M, et al. A randomized, double-blind, placebo-controlled study to assess the safety and efficacy of pulsed, inhaled nitric oxide (iNO) in subjects at risk of pulmonary hypertension (PH) associated with fibrotic interstitial lung disease (fILD) on long term oxygen therapy. Am J Respir Crit Care Med. 2020;201:A2757.

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