A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis.

Published

Journal Article

BACKGROUND: Sildenafil, a phosphodiesterase-5 inhibitor, may preferentially improve blood flow to well-ventilated regions of the lung in patients with advanced idiopathic pulmonary fibrosis, which could result in improvements in gas exchange. We tested the hypothesis that treatment with sildenafil would improve walk distance, dyspnea, and quality of life in patients with advanced idiopathic pulmonary fibrosis, defined as a carbon monoxide diffusion capacity of less than 35% of the predicted value. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of sildenafil in two periods. The first period consisted of 12 weeks of a double-blind comparison between sildenafil and a placebo control. The primary outcome was the proportion of patients with an increase in the 6-minute walk distance of 20% or more. Key secondary outcomes included changes in oxygenation, degree of dyspnea, and quality of life. The second period was a 12-week open-label evaluation involving all patients receiving sildenafil. RESULTS: A total of 180 patients were enrolled in the study. The difference in the primary outcome was not significant, with 9 of 89 patients (10%) in the sildenafil group and 6 of 91 (7%) in the placebo group having an improvement of 20% or more in the 6-minute walk distance (P=0.39). There were small but significant differences in arterial oxygenation, carbon monoxide diffusion capacity, degree of dyspnea, and quality of life favoring the sildenafil group. Serious adverse events were similar in the two study groups. CONCLUSIONS: This study did not show a benefit for sildenafil for the primary outcome. The presence of some positive secondary outcomes creates clinical equipoise for further research. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00517933.)

Full Text

Duke Authors

Cited Authors

  • Idiopathic Pulmonary Fibrosis Clinical Research Network, ; Zisman, DA; Schwarz, M; Anstrom, KJ; Collard, HR; Flaherty, KR; Hunninghake, GW

Published Date

  • August 12, 2010

Published In

Volume / Issue

  • 363 / 7

Start / End Page

  • 620 - 628

PubMed ID

  • 20484178

Pubmed Central ID

  • 20484178

Electronic International Standard Serial Number (EISSN)

  • 1533-4406

Digital Object Identifier (DOI)

  • 10.1056/NEJMoa1002110

Language

  • eng

Conference Location

  • United States