TABLE 5.
Recent seminal studies with vasodilator therapies in IPF and other ILD cohorts.
| Study | Year | Population | Number patients | Primary endpoint | Outcome |
|---|---|---|---|---|---|
|
INCREASE 111 Treprostinil Versus placebo Phase 2/3 |
2021 | ILD with PH confirmed by right heart catheter | 326 | Change in 6MWD at 16‐weeks | Improved 6MWD in treatment arm of 31.12 m (95% CI, 16.85–45.39; p < 0.001); improved NT‐proBNP, reduced clinical worsening, compared with control arm. |
|
Sildenafil plus pirfenidone versus placebo plus pirfenidone 68 Phase 2b |
2021 | IPF with DLCO ≤40% predicted and mPAP ≥20 mm Hg | 177 | Proportion with disease progression (change in 6MWD, respiratory hospitalization, death) at 52‐weeks |
No difference in the primary endpoint, between‐group difference 3.06% (95% CI –11.30 to 17.97; p = 0.65). |
|
RISE‐IIP 112 Riociguat versus placebo Phase 2b |
2019 | IIP with PH confirmed by right heart catheter | 147 | Change in 6MWD at 26‐weeks | No difference in the primary endpoint or time to clinical worsening; trial terminated early due to increased SAEs including death in treatment arm. |
|
INSTAGE 113 Sildenafil plus nintedanib versus placebo plus nintedanib Phase 3 |
2018 | IPF patients with DLCO ≤35% predicted | 274 | Change in baseline total SGRQ score at 12‐weeks |
No difference in mean change in SGRQ score (treatment arm −1.28 points, control arm −0.77 points; p = 0.72). No difference in dyspnoea scores or safety. |
|
BPHIT 114 Bosentan versus placebo Phase 2 |
2014 | Fibrotic IIP with right heart catheter confirmed PH | 60 | Fall from baseline pulmonary vascular resistance index of 20% or more at 16 weeks | No difference in invasive pulmonary haemodynamics, functional capacity or symptoms. |
|
ARTEMIS‐IPF 115 Ambrisentan versus placebo Phase 3 |
2013 | IPF patients with ≤5% honeycombing on HRCT scan | 492 | Time to disease progression (death, respiratory hospitalization, decrease in FVC and DLCO); 48‐week assessment |
Increased disease progression in treatment arm (90 [27.4%] vs. 28 [17.2%] patients; p < 0.010; hazard ratio, 1.74 [95% CI, 1.14–2.66]) |
|
STEP‐IPF 116 Sildenafil versus placebo Phase 3 |
2010 | IPF patients with DLCO ≤35% predicted | 180 |
Proportion of patients with an increase in 6MWD ≥20% |
No difference in proportion meeting primary endpoint (treatment arm 10%, control arm 7%; p = 0.39); some secondary endpoints improved with treatment |
Abbreviations: 6MWD, six‐minute walk distance; DLCO, diffusing capacity for carbon monoxide; FVC, forced vital capacity.; HRCT, high resolution computed tomography; IIP, idiopathic interstitial pneumonia; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; mPAP, mean pulmonary artery pressure; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; PH, pulmonary hypertension; SAE, serious adverse event; SGRQ, St George's Respiratory Questionnaire.