Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials.

摘要: Summary Background Idiopathic pulmonary fibrosis is a progressive and fatal lung disease with inevitable loss of function. The CAPACITY programme (studies 004 006) was designed to confirm the results phase 2 study that suggested pirfenidone, novel antifibrotic anti-inflammatory drug, reduces deterioration in function patients idiopathic fibrosis. Methods In two concurrent trials (004 006), (aged 40–80 years) were randomly assigned oral pirfenidone or placebo for minimum 72 weeks 110 centres Australia, Europe, North America. 004, 2:1:2 ratio 2403 mg/day, 1197 placebo; 006, 1:1 mg/day placebo. randomisation code (permuted block design) computer generated stratified by region. All personnel masked treatment group assignment until after final database lock. Treatments administered orally, 801 mg 399 three times day. primary endpoint change percentage predicted forced vital capacity (FVC) at week 72. Analysis intention treat. studies are registered ClinicalTrials.gov, numbers NCT00287729 NCT00287716. Findings 174 435 87 171 344 173 both analysed. reduced decline FVC (p=0·001). Mean −8·0% (SD 16·5) −12·4% (18·5) (difference 4·4%, 95% CI 0·7 9·1); 35 (20%) versus 60 (35%) patients, respectively, had least 10%. A significant effect noted all timepoints from 24 an analysis over (p=0·0007). intermediate groups. difference between groups not (p=0·501). −9·0% 19·6) −9·6% (19·1) group, (0·6%, −3·5 4·7); however, consistent apparent 48 (p=0·005) (p=0·007). Patients higher incidences nausea (125 [36%] 345 vs [17%] 347), dyspepsia (66 [19%] 26 [7%]), vomiting (47 [14%] 15 [4%]), anorexia (37 [11%] 13 photosensitivity (42 [12%] 6 [2%]), rash (111 [32%] 40 [12%]), dizziness (63 [18%] [10%]) than did those group. Fewer overall deaths (19 [6%] 29 [8%]) fewer related (12 [3%] 25 [7%]) occurred Interpretation data show has favourable benefit risk profile represents appropriate option Funding InterMune.