Study name | Treatment 1 | Treatment 2 | Study design | Primary endpoint(s) | Results |

IFIGENIA [14] | Prednisone + azathioprine + NAC (n=80) | Prednisone + azathioprine (n=75) | Phase-III, randomised | Change in VC and D_{LCO} from baseline at month 12 | Significant benefits from triple therapy were demonstrated for both endpoints Absolute between-group differences for mean change from baseline in VC and D_{LCO} at month 12 were 0.18 L (95% CI: 0.03–0.32; p=0.02) and 0.75 mmol·min^{−1}·kPa^{−1} (95% CI: 0.27–1.23; p=0.003), respectively |

PANTHER-IPF [15] | NAC + prednisone + azathioprine (n=77)^{#} | Placebo (n=131) | Phase-III, randomised | Change in FVC from baseline at week 60 | The NAC + prednisone + azathioprine arm was terminated due to an increased rate of death and hospitalisation versus a placebo |

PANTHER-IPF [16] | NAC (n=133) | Placebo (n=131) | Phase-III, randomised | Change in FVC from baseline at week 60 | No significant difference was observed between NAC and a placebo for the primary endpoint (mean changes in FVC of −0.18 L and −0.19 L, respectively; p=0.77) |

Interferon gamma-1b trial [17] | Interferon gamma-1b (n=162) | Placebo (n=168) | Phase-III, randomised | Time to disease progression (decline in FVC ≥10% of predicted or increase in P_{(A–a)O2} of ≥5 mmHg at rest) or death | No significant difference was observed between interferon gamma-1b and a placebo for the primary endpoint (median of 439 and 344 days, respectively; p=0.5) |

INSPIRE [18] | Interferon gamma-1b (n=551) | Placebo (n=275) | Phase-III, randomised | Survival | Trial was terminated when an interim analysis showed no significant difference between interferon gamma-1b and a placebo for the primary endpoint (HR 1.15; 95% CI: 0.77–1.71; p=0.50) |

ACE-IPF [19] | Warfarin (n=72) | Placebo (n=73) | Phase-III, randomised | Composite of time to death, hospitalisation (non-bleeding, non-elective), or absolute decline in FVC ≥10% of predicted | Trial terminated after mean follow-up of 28 weeks, when interim analysis showed higher mortality with warfarin versus a placebo (14 deaths versus 3 deaths; p=0.005) |

BUILD-1 [20] | Bosentan (n=74) | Placebo (n=84) | Phase-III, randomised | Change in 6-MWD from baseline at month 12 | No significant difference was observed between bosentan and a placebo for the primary endpoint (mean changes of −52 m and −34 m, respectively; p=0.23) |

BUILD-3 [21] | Bosentan (n=407) | Placebo (n=209) | Phase-III, randomised | Time to worsening of IPF (decline in FVC ≥10% of predicted and decline in D_{LCO} ≥15% of predicted, or acute exacerbation) or death | No significant difference was observed between bosentan and a placebo for the primary endpoint (HR 0.85; 95% CI: 0.66–1.10; p=0.21) |

MUSIC [22] | Macitentan (n=119) | Placebo (n=59) | Phase-II, randomised | Change in FVC from baseline at month 12 | No significant difference was observed between macitentan and a placebo for the primary endpoint (median change of −0.20 L in both groups) |

ARTEMIS-IPF [23] | Ambrisentan (n=329) | Placebo (n=163) | Phase-III, randomised | Time to disease progression (defined as death, respiratory hospitalisation, or categorical decline in lung function (FVC ≥10% of predicted plus D_{LCO} ≥5% of predicted, or FVC ≥5% of predicted plus D_{LCO} ≥15% of predicted) (event-driven) | Trial terminated after interim analysis showed a low likelihood of demonstrating efficacy on the primary endpoint |

Etanercept trial [24] | Etanercept (n=46) | Placebo (n=41) | Phase-II, randomised | Changes in FVC (% predicted), D_{LCO} (% predicted), and P_{(A–a)O2} (at rest) from baseline at week 48 | No significant differences were observed between etanercept and a placebo for the lung function endpoints |

STEP-IPF [25] | Sildenafil (n=89) | Placebo (n=91) | Phase-III, randomised for 12 weeks followed by 12-week open-label extension | ≥20% increase in 6-MWD at week 12 | No significant difference was observed between sildenafil and a placebo on the primary endpoint (10% and 7% of patients, respectively; p=0.39) |

Imatinib trial [26] | Imatinib (n=59) | Placebo (n=60) | Phase-II, randomised for 96 weeks | Time to disease progression (defined as decline in FVC from baseline of >10% of predicted) or death | No significant difference was observed between imatinib and a placebo on the primary endpoint (HR 1.05; 95% CI: 0.56–1.96; p=0.89) |

Simtuzumab trial [27] | Simtuzumab (n=272) | Placebo (n=272) | Phase-II, randomised | Progression-free survival (defined as death or a categorical decline in FVC (% predicted) from baseline, i.e. ≥10% relative decline and ≥5% absolute decline) | Trial was terminated when interim analysis showed no significant difference between simtuzumab and a placebo on progression-free survival (HR 1.13; 95% CI: 0.88–1.45; p=0.33) |

Pirfenidone trial [28] | Pirfenidone (n=72)^{¶} | Placebo (n= 35) | Phase-II, randomised, in Japanese patients | Change from baseline in lowest S_{pO2} during a 6-min steady-state exercise test at month 6 | Trial terminated when interim analysis showed no significant difference between pirfenidone and a placebo for the primary endpoint at month 6 (increase of 0.64% versus decrease of 0.55%, respectively; p=0.15) |

Pirfenidone trial [29] | Pirfenidone (n=55-108)^{+} | Placebo (n=104) | Phase-III, randomised in Japanese patients | Original: change from baseline in lowest S_{pO2} during a 6-min steady-state exercise test at week 52Revised: change in VC from baseline at week 52 | Significant benefits were seen with high-dose pirfenidone versus a placebo for change in VC at week 52 (−0.09 L versus −0.16 L; p=0.0416) |

CAPACITY [30] | Pirfenidone (n=87–345)^{§} | Placebo (n=347) | Phase-III, randomised (two trials) | Change in FVC (% predicted) from baseline at week 72 | Significant benefits were observed with pirfenidone (dose: 2403 mg·day^{−1}) versus a placebo for the primary endpoint in CAPACITY-2 (−8.0% versus −12.4%; p=0.001) but not in CAPACITY-1 (−9.0% versus −9.6%, respectively; p=0.50) |

ASCEND [31] | Pirfenidone (n=278)^{ƒ} | Placebo (n=277) | Phase-III, randomised | Change in FVC (% predicted) from baseline at week 52 | Significant benefits were observed for pirfenidone versus a placebo for the primary endpoint (p<0.001) |

TOMORROW [32] | Nintedanib (n=85–86)^{##} | Placebo (n=85) | Phase-II, randomised | Annual rate of decline in FVC | Reduced FVC decline with nintedanib (150 mg twice daily) versus a placebo (−0.06 L versus −0.19 L; p=0.06 with closed testing procedure; p=0.01 with hierarchical testing procedure) |

INPULSIS [33] | Nintedanib (n=638)^{¶¶} | Placebo (n=423) | Phase-III, randomised (two trials) | Annual rate of decline in FVC | Significant benefits were observed for nintedanib versus a placebo for the primary endpoint in INPULSIS-1 (−114.7 mL versus −239.9 mL; p<0.001) and INPULSIS-2 (−113.6 mL versus −207.3 mL; p<0.001) |

NAC: N-acetylcysteine; VC: vital capacity; *D*_{LCO}: diffusing capacity of the lung for carbon monoxide; FVC: forced vital capacity; HR: hazard ratio; *P*_{(A-a)O2}: alveolar to arterial oxygen pressure difference; 6-MWD: 6-min walk distance; *S*_{pO2}: arterial oxygen saturation measured by pulse oximetry. ^{#}: compared with NAC (n=81) and placebo (n=78); ^{¶}: 200–600 mg (three times daily); ^{+}: pirfenidone dose: high (n=108), low (n=55); ^{§}: pirfenidone dose: 1197 mg·day^{−1} (n=87), 2403 mg·day^{−1} (n=345); ^{ƒ}: pirfenidone dose: 2403 mg·day^{−1}; ^{##}: nintedanib dose: 50 mg once daily (n=86), 50 mg twice daily (n=86), 100 mg twice daily (n=86), 150 mg twice daily (n=85); ^{¶¶}: nintedanib dose: 150 mg twice daily.