Randomized trial of zileuton for treatment of COPD exacerbations requiring
hospitalization.
Author(s): Woodruff PG, Albert RK, Bailey WC, Casaburi R, Connett JE, Cooper JA Jr, Criner
GJ, Curtis JL, Dransfield MT, Han MK, Harnden SM, Kim V, Marchetti N, Martinez
FJ, McEvoy CE, Niewoehner DE, Reilly JJ, Rice K, Scanlon PD, Scharf SM, Sciurba
FC, Washko GR, Lazarus SC; Copd Clinical Research Network.
Affiliation(s): Division of Pulmonary and Critical Care Medicine, University of California, San
Francisco, San Francisco, California, USA. Prescott.woodruff@ucsf.edu
Publication date & source: 2011, COPD. , 8(1):21-9
RATIONALE: Leukotrienes have been implicated in the pathogenesis of acute
exacerbations of COPD, but leukotriene modifiers have not been studied as a
possible therapy for exacerbations.
OBJECTIVE: We sought to test the safety and efficacy of adding oral zileuton (a
5-lipoxygenase inhibitor) to usual treatment for acute exacerbations of COPD
requiring hospitalization.
METHODS: Randomized double-blind, placebo-controlled, parallel group study of
zileuton 600 mg orally, 4 times daily versus placebo for 14 days starting within
12 hours of hospital admission for COPD exacerbation. Primary outcome measure was
hospital length of stay; secondary outcomes included treatment failure and
biomarkers of leukotriene production.
MAIN FINDINGS: Sixty subjects were randomized to zileuton and 59 to placebo (the
study was stopped short of enrollment goals because of slow recruitment). There
was no difference in hospital length of stay (3.75 +/- 2.19 vs. 3.86 +/- 3.06
days for zileuton vs. placebo, p = 0.39) or treatment failure (23% vs. 27% for
zileuton vs. placebo, p = 0.63) despite a decline in urinary LTE(4) levels in the
zileuton-treated group as compared to placebo at 24 hours (change in natural
log-transformed ng/mg creatinine -1.38 +/- 1.19 vs. 0.14 +/- 1.51, p < 0.0001)
and 72 hours (-1.32 +/- 2.08 vs. 0.26 +/- 1.93, p<0.006). Adverse events were
similar in both groups.
PRINCIPAL CONCLUSIONS: While oral zileuton during COPD exacerbations that require
hospital admission is safe and reduces urinary LTE(4) levels, we found no
evidence suggesting that this intervention shortened hospital stay, with the
limitation that our sample size may have been insufficient to detect a modest but
potentially meaningful clinical improvement.
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