TY - JOUR
T1 - A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis
AU - Noth, Imre
AU - Anstrom, Kevin J.
AU - Calvert, Sara Bristol
AU - De Andrade, Joao
AU - Flaherty, Kevin R.
AU - Glazer, Craig
AU - Kaner, Robert J.
AU - Olman, Mitchell A.
PY - 2012/7/1
Y1 - 2012/7/1
N2 - 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.
AB - 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.
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U2 - 10.1164/rccm.201202-0314OC
DO - 10.1164/rccm.201202-0314OC
M3 - Article
C2 - 22561965
AN - SCOPUS:84863450246
SN - 1073-449X
VL - 186
SP - 88
EP - 95
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 1
ER -