title: Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis.
abstract: BACKGROUND
  A combination of prednisone, azathioprine, and N-acetylcysteine (NAC) has been widely used as a treatment for idiopathic pulmonary fibrosis. The safety and efficacy of this three-drug regimen is unknown.
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled trial, we assigned patients with idiopathic pulmonary fibrosis who had mild-to-moderate lung-function impairment to one of three groups -- receiving a combination of prednisone, azathioprine, and NAC (combination therapy), NAC alone, or placebo -- in a 1:1:1 ratio. The primary outcome was the change in longitudinal measurements of forced vital capacity during a 60-week treatment period.
  
  
  RESULTS
  When approximately 50% of data had been collected (with 77 patients in the combination-therapy group and 78 in the placebo group), a planned interim analysis revealed that patients in the combination-therapy group, as compared with the placebo group, had an increased rate of death (8 vs. 1, P=0.01) and hospitalization (23 vs. 7, P<0.001). These observations, coupled with no evidence of physiological or clinical benefit for combination therapy, prompted the independent data and safety monitoring board to recommend termination of the combination-therapy group at a mean follow-up of 32 weeks. Data from the ongoing comparison of the NAC-only group and the placebo group are not reported here.
  
  
  CONCLUSIONS
  Increased risks of death and hospitalization were observed in patients with idiopathic pulmonary fibrosis who were treated with a combination of prednisone, azathioprine, and NAC, as compared with placebo. These findings provide evidence against the use of this combination in such patients. (Funded by the National Heart, Lung, and Blood Institute and the Cowlin Family Fund; ClinicalTrials.gov number, NCT00650091.).
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raghu
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Anstrom
authors.forename: Talmadge E
authors.initials: TE
authors.lastname: King
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Lasky
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
mesh_terms: D000111:Acetylcysteine / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D001379:Azathioprine; D011241:Prednisone; D000111:Acetylcysteine