Interstitial lung disease (ILD) randomised controlled trials using 6-min walk test (6MWT) as the primary end-point
| Patient population | Treatment arms | Primary end-point | Primary end-point findings | |
| Studies in advanced ILD/ILD-PH populations | ||||
| STEP-IPF (NCT00517933) [17] | Patients with advanced IPF, defined as DLCO <35% predicted (n=180) | Sildenafil (a PAH drug) versus placebo | The proportion of patients with ≥20% improvement in 6MWD from baseline to week 12 | Primary end-point not met (10% versus 7% for sildenafil versus placebo, respectively; ns) |
| RISE-IIP (NCT02138825) [19] | Patients with IIP-PH (with FVC ≥45% and 6MWD 150–450 m; n=147) | Riociguat (a PAH drug) versus placebo | Change in 6MWD from baseline to week 26 | Primary end-point not met (least squares mean (95% CI) treatment difference of 21 (−9–52) m; ns) |
| INCREASE (NCT02630316) [20] | Patients with ILD-PH (n=326) | Inhaled treprostinil (a PAH drug) versus placebo | Change in peak 6MWD from baseline to week 16 | Primary end-point was met (least squares mean (95% CI) treatment difference of 31.12 (16.85–45.39) m; p<0.001) |
| Studies in general ILD populations | ||||
| Phase 2 trial of pirfenidone [14] | Patients with IPF (n=109) | Pirfenidone (an antifibrotic) versus placebo | Change in the nadir SpO2 during the 6MWT from baseline to months 6 and 9 | Primary end-point not met (mean±sd of 0.47±3.88% versus −0.94±3.36% at month 9 for pirfenidone versus placebo, respectively; ns) |
| BUILD-1 (NCT00071461) [15] | Patients with IPF with severe disease excluded (FVC <50% or DLCO <30%; n=154) | Bosentan (a PAH drug) versus placebo | Change in 6MWD from baseline to month 12 | Primary end-point not met (mean±sd treatment difference of −18±20 m; ns) |
| BUILD-2 (NCT00070590) [16] | Patients with SSc-ILD with severe disease excluded (FVC <40% or DLCO <30%; n=163) | Bosentan (a PAH drug) versus placebo | Change in 6MWD from baseline to month 12 | Primary end-point not met (median (95% CI) treatment difference of −8 (−27–9) m; ns) |
| Phase 2 trial of pirfenidone plus NAC (NCT01504334) [18] | Patients with IPF with severe disease excluded (FVC <45% or DLCO <30%; n=76) | Pirfenidone (an antifibrotic) + oral NAC versus placebo + oral NAC | Change in the maximal 6MWD and the nadir SpO2 during the 6MWT from baseline to week 48 (plus change in FVC from baseline to week 48) | Primary end-point not met (for 6MWD mean±sd of 13.82±125.19 m versus −5.13±85.48 m, ns; for SpO2 mean±sd of −4.25±7.27% versus−5.31±5.49% for pirfenidone + oral NAC versus placebo + oral NAC, ns) |
PH: pulmonary hypertension; IPF: idiopathic pulmonary fibrosis; IIP: idiopathic interstitial pneumonia; NAC: N-acetylcysteine; DLCO: diffusing capacity of the lung for carbon monoxide; PAH: pulmonary arterial hypertension; 6MWD: 6-min walk distance; ns: nonsignificant; FVC: forced vital capacity; SpO2: peripheral oxygen saturation; SSc: systemic sclerosis.