Increased risks of death and hospitalization were observed in patients with idiopathic pulmonary fibrosis who were treated with a combination of prednisone, azathioprine, and N–acetylcysteine (NAC), as compared with placebo. These findings provide evidence against the use of this combination in such patients.Methods
- In this randomized, double–blind, placebo–controlled trial, the authors 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.
- 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.