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Published ahead of print on January 21, 2005, doi:10.1164/rccm.200404-571OC
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American Journal of Respiratory and Critical Care Medicine Vol 171. pp. 1040-1047, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200404-571OC

Original Article

Double-blind, Placebo-controlled Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis

Arata Azuma, Toshihiro Nukiwa, Eiyasu Tsuboi, Moritaka Suga, Shosaku Abe, Koichiro Nakata, Yoshio Taguchi, Sonoko Nagai, Harumi Itoh, Motoharu Ohi, Atsuhiko Sato, Shoji Kudoh for the members of the Research Group for Diffuse Lung Diseases in Japan; and Ganesh Raghu

Fourth Department of Internal Medicine, Nippon Medical School; Division of Respiratory Disease, Toranomon Hospital, Tokyo; Department of Respiratory Oncology and Molecular Medicine Division of Cancer Control Institute of Development, Aging, and Cancer, Tohoku University, Sendai; Department of Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto; Third Department of Internal Medicine and Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo; Department of Respiratory Medicine, Tenri Hospital, Tenri; Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University; Kyoto Preventive Medical Center, Kyoto; Department of Radiology, Fukui Medical School, Fukui; Sleep Medical Center, Osaka Kaisei Hospital, Osaka, Japan; and University of Washington Medical Center, Seattle, Washington

Correspondence and requests for reprints should be addressed to Ganesh Raghu, M.D., Division of Pulmonary & Critical Care Medicine, Campus Box 356522, University of Washington, Seattle, WA 98195-6522. E-mail: graghu{at}u.washington.edu

Idiopathic pulmonary fibrosis (IPF) is a fatal disorder without an effective therapy to date. In a double-blind, randomized, placebo-controlled trial, 107 patients were prospectively evaluated for efficacy of a novel compound, pirfenidone. The difference in the change in the lowest oxygen saturation by pulse oximetry (SpO2) during a 6-minute exercise test, the primary endpoint, from baseline to 6 months was not significant between the two groups (p = 0.0722). In a prespecified subset of patients who maintained a SpO2 greater than 80% during a 6-minute exercise test at baseline, the lowest SpO2 improved during a 6-minute exercise test in the pirfenidone group at 6 and 9 months (p = 0.0069 and 0.0305, respectively). Positive treatment effect was demonstrated in secondary endpoints: (1) change in VC measurements at 9 months (p = 0.0366) and (2) episodes of acute exacerbation of IPF occurring exclusively in the placebo group during the 9 months (p = 0.0031). Significant adverse events were associated with pirfenidone; however, adherence to treatment regimen was similar between pirfenidone and placebo groups. In conclusion, treatment with pirfenidone improved VC and prevented acute exacerbation of IPF during the 9 months of follow-up. Future long-term studies are needed to clarify the overall safety and efficacy of pirfenidone in IPF.

Key Words: acute exacerbation • antifibrotic agent • idiopathic pulmonary fibrosis • pirfenidone • 6-minute steady-state exercise test




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