A Controlled Trial of Sildenafil in Advanced Idiopathic Pulmonary Fibrosis

N Engl J Med. 2010 Aug 12;363(7):620-8. doi: 10.1056/NEJMoa1002110. Epub 2010 May 18.

Abstract

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.)

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Double-Blind Method
  • Dyspnea / drug therapy
  • Dyspnea / etiology
  • Exercise Test
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Idiopathic Pulmonary Fibrosis / mortality
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Male
  • Middle Aged
  • Oxygen / blood
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Pulmonary Diffusing Capacity
  • Purines / adverse effects
  • Purines / therapeutic use
  • Quality of Life*
  • Respiratory Function Tests
  • Sildenafil Citrate
  • Sulfones / adverse effects
  • Sulfones / therapeutic use*
  • Treatment Outcome
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / therapeutic use*

Substances

  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • Sildenafil Citrate
  • Oxygen

Associated data

  • ClinicalTrials.gov/NCT00517933