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

Research output: Contribution to journalArticle

293 Citations (Scopus)

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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Idiopathic Pulmonary Fibrosis
Warfarin
Randomized Controlled Trials
Placebos
International Normalized Ratio
Hospitalization
Clinical Trials Data Monitoring Committees
Point-of-Care Systems
Mortality
Pulmonary Fibrosis
Therapeutics
Home Care Services
Outcome Assessment (Health Care)
Equipment and Supplies

ASJC Scopus subject areas

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

Cite this

A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. / Noth, Imre; Anstrom, Kevin J.; Calvert, Sara Bristol; De Andrade, Joao; Flaherty, Kevin R.; Glazer, Craig; Kaner, Robert J.; Olman, Mitchell A.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 186, No. 1, 01.07.2012, p. 88-95.

Research output: Contribution to journalArticle

Noth, Imre ; Anstrom, Kevin J. ; Calvert, Sara Bristol ; De Andrade, Joao ; Flaherty, Kevin R. ; Glazer, Craig ; Kaner, Robert J. ; Olman, Mitchell A. / A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. In: American Journal of Respiratory and Critical Care Medicine. 2012 ; Vol. 186, No. 1. pp. 88-95.
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