A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis

Imre Noth, Kevin J. Anstrom, Sara Bristol Calvert, Joao De Andrade, Kevin R. Flaherty, Craig Glazer, Robert J. Kaner, Mitchell A. Olman

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296 Scopus citations

Abstract

Rationale: Animal and human studies support the importance of the coagulation cascade in pulmonary fibrosis. Objectives: In a cohort of subjects with progressive idiopathic pulmonary fibrosis (IPF), we tested the hypothesis that treatment with warfarin at recognized therapeutic doses would reduce rates of mortality, hospitalization, and declines in FVC. Methods: This was a double-blind, randomized, placebo-controlled trial of warfarin targeting an international normalized ratio of 2.0 to 3.0 in patients with IPF. Subjects were randomized in a 1:1 ratio to warfarin or matching placebo for a planned treatment period of 48 weeks. International normalized ratios were monitored using encrypted home point-of-care devices that allowed blinding of study therapy. Measurements and Main Results: The primary outcome measure was the composite outcome of time to death, hospitalization (nonbleeding, nonelective), or a 10%or greater absolute decline in FVC. Due to a low probability of benefit and an increase in mortality observed in the subjects randomized to warfarin (14 warfarin versus 3 placebo deaths; P = 0.005) an independent Data and Safety Monitoring Board recommended stopping the study after 145 of the planned 256 subjects were enrolled (72 warfarin, 73 placebo). The mean follow-up was 28 weeks.

Original languageEnglish (US)
Pages (from-to)88-95
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume186
Issue number1
DOIs
StatePublished - Jul 1 2012

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ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Noth, I., Anstrom, K. J., Calvert, S. B., De Andrade, J., Flaherty, K. R., Glazer, C., Kaner, R. J., & Olman, M. A. (2012). A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine, 186(1), 88-95. https://doi.org/10.1164/rccm.201202-0314OC