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Randomized Controlled Trial
. 2012 Jul 1;186(1):88-95.
doi: 10.1164/rccm.201202-0314OC. Epub 2012 May 3.

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

Imre Noth  1 , Kevin J Anstrom, Sara Bristol Calvert, Joao de Andrade, Kevin R Flaherty, Craig Glazer, Robert J Kaner, Mitchell A Olman; Idiopathic Pulmonary Fibrosis Clinical Research Network (IPFnet)
Affiliations
Randomized Controlled Trial

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

Imre Noth et al. Am J Respir Crit Care Med. .

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.

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.

Trial registration: ClinicalTrials.gov NCT00957242.

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Figures

Figure 1.
Figure 1.
Enrollment and outcomes. IPF = idiopathic pulmonary fibrosis.
Figure 2.
Figure 2.
(A) Comparison of warfarin with placebo for the primary endpoint. (B) Comparison of warfarin versus placebo for time to all-cause mortality. (C) Comparison of warfarin versus placebo for time to all-cause mortality or all-cause hospitalization.
Figure 3.
Figure 3.
Mortality listing with clinical events. IPF = idiopathic pulmonary fibrosis.
Figure 4.
Figure 4.
Subgroup analysis of the key clinical subgroups. DlCO = diffusing capacity of carbon monoxide.
See this image and copyright information in PMC

Comment in

References

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