A Placebo-Controlled Randomized Trial of Warfarin in Idiopathic Pulmonary Fibrosis

A Placebo-Controlled Randomized Trial of Warfarin in
Idiopathic Pulmonary Fibrosis

Imre Noth¹, Kevin J. Anstrom², Sara Bristol Calvert², Joao de Andrade³, Kevin R. Flaherty⁴,
Craig Glazer⁵, Robert J. Kaner⁶, and Mitchell A. Olman⁷; for the Idiopathic Pulmonary Fibrosis Clinical Research Network (IPFnet)*

¹University of Chicago, Chicago, Illinois; ²Duke Clinical Research Institute, Durham, North Carolina; ³University of Alabama, Birmingham, Alabama; ⁴National Jewish Medical Center, Denver, Colorado; ⁵University of Texas Southwestern, Dallas, Texas; ⁶Weill Cornell Medical College, New York,
New York; and ⁷Cleveland Clinic, Cleveland, Ohio

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 encryptedhomepoint-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 a10%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.

Conclusions: This study did not show a benefit for warfarin in the treatment of patients with progressive IPF. Treatment with warfarin was associated with an increased risk of mortality in an IPF population who lacked other indications for anticoagulation.

Clinical trial registered with www.clinicaltrials.gov (NCT00957242).

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