TABLE 1.
Major randomised controlled trials of antifibrotics among patients with idiopathic pulmonary fibrosis (IPF)
| Phase | Patients | Intervention | Duration | Primary outcome(s) | Key secondary outcome(s) | |
| Nintedanib | ||||||
| TOMORROW [25] | II | 432 | Randomised to 1 of 4 doses nintedanib or placebo | 52 weeks | Annual rate of FVC decline 60 mL·year−1 in nintedanib 150 mg twice daily group versus 190 mL·year−1 in placebo group | Lower incidence of AE-IPF, small decrease in SGRQ with nintedanib 150 mg twice daily |
| INPULSUS I [7] | III | 515 IPF patients | Randomised 3:2 ratio to nintedanib 150 mg twice daily or placebo | 52 weeks | Annual rate of decline FVC −114.7 mL nintedanib versus −239.9 mL placebo (p<0.01) | No significant difference in time to first AE or proportion with AE |
| INPULSIS II [7] | III | 551 IPF patients | Randomised 3:2 ratio to nintedanib 150 mg twice daily or placebo | 52 weeks | Annual rate of decline FVC −113.6 mL nintedanib versus −207.3 mL placebo (p<0.01) | Increase in time to first AE in nintedanib group and lower proportion with AE in nintedanib group; significant small increase in SGRQ in nintedanib group |
| Pirfenidone | ||||||
| CAPACITY I (004) [26] | III | 435 IPF patients | Randomised 2:1:2 pirfenidone 2403 mg·day−1, pirfenidone 1197 mg·day−1 or placebo | 72 weeks | Mean decline FVC −8% pirfenidone versus −12.4% placebo (p<0.01) | Decreased proportion of patients with ≥10% decline in FVC; prolonged PFS |
| CAPACITY II (006) [26] | III | 344 IPF patients | Randomised 1:1 pirfenidone 2403 mg·day−1 or placebo | 72 weeks | Mean decline FVC −9% pirfenidone versus −9.6% placebo (p=0.5) | Reduced decline in 6MWD |
| ASCEND [8] | III | 555 with IPF (surgical biopsy required if possible UIP) | Randomised to pirfenidone 801 mg three times daily or placebo | 52 weeks | Proportion of patients with ≥10% decline in FVC or death reduced by 47.9% pirfenidone versus placebo (p<0.01) | Decreased decline in 6MWD, improved PFS |
| Combination nintedanib and pirfenidone | ||||||
| Safety and pharmacokinetics of nintedanib and pirfenidone in IPF [27] | II | n=50: 25 patients on pirfenidone ≥3 months; 25 patients not on antifibrotic | Nintedanib (100 mg twice daily or 150 mg twice daily) or placebo added to pirfenidone | 14 days (100 mg), 28 days (150 mg) | Adverse events: 10 out of 21 patients on combination; 9 out of 17 patients on only nintedanib | Nintedanib did not affect pharmacokinetics of pirfenidone |
FVC: forced vital capacity; AE: adverse event; SGRQ: St George's Respiratory Questionnaire; PFS: progression-free survival; 6MWD: 6-min walk distance; UIP: usual interstitial pneumonia.