Pulmonary hypertension (PH) complicating idiopathic interstitial pneumonias (IIPs) is associated with impaired functional ability and poor outcomes. Whether treating PH in IIP is beneficial remains unknown.
RISE-IIP (NCT02138825) was a randomised, placebo (PBO)-controlled study to evaluate the efficacy and safety of riociguat in patients with IIP, FVC ≥45% predicted and mean pulmonary artery pressure ≥25 mmHg.
Patients were randomised to riociguat up to 2.5 mg tid or PBO for 26 weeks followed by an open-label extension where all patients received riociguat. The primary endpoint was change from baseline to week 26 in 6-minute walk distance (6MWD). Secondary endpoints included clinical worsening (all-cause mortality, hospitalisation due to worsening cardiopulmonary status, 15% decrease in 6MWD or worsening of WHO FC).
Of 147 randomised patients, 73 received riociguat and 74 PBO. The study was stopped early (mean treatment duration 121±66 days) at the recommendation of the Data Monitoring Committee due to increased SAEs (37% riociguat vs 23% PBO in the blinded phase) and increased mortality in riociguat patients. There were 11 deaths in the blinded phase (8 riociguat, 3 PBO), and 9 in the extension (1 former riociguat, 8 former PBO). Riociguat did not improve 6MWD vs PBO at 26 week (least squares mean difference +21 m; 95% CI –9 to +52 m). There was no difference in proportion of subjects with clinical worsening: 47% riociguat vs 49% PBO.
In patients with PH-IIP, riociguat was associated with increased SAEs and mortality, and an unfavourable risk:benefit ratio. The current study did not reveal a potential aetiology for the observed mortality effect.