Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization

Prescott G. Woodruff, Richard K. Albert, William C. Bailey, Richard Casaburi, John E. Connett, John A D Cooper, Gerard J. Criner, Jeffrey L. Curtis, Mark T. Dransfield, Meilan K. Han, Sarah M. Harnden, Victor Kim, Nathaniel Marchetti, Fernando J. Martinez, Charlene E. McEvoy, Dennis E. Niewoehner, John J. Reilly, Kathryn Rice, Paul D. Scanlon, Steven M. ScharfFrank C. Sciurba, George R. Washko, Stephen C. Lazarus

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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 LTE4 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 LTE4 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.

Original languageEnglish (US)
Pages (from-to)21-29
Number of pages9
JournalCOPD: Journal of Chronic Obstructive Pulmonary Disease
Issue number1
StatePublished - Feb 2011

Bibliographical note

Funding Information:
FJM has received speaking, consultancy and steering committee fees from GlaxoSmithKline and Nycomed. He has received speaking and consulting fees from Medimmune/Astra Zeneca, Boehringer Ingelheim (BI) and Schering. He has received consulting and steering committee fees from Actelion. He has received consulting and DSMB fees from Novartis. He has received consulting fees from Forest/Almirall, Roche, Bayer and HLS. He has received advisory board fees from Merck, Pearl, UBC, Mpex, Talecris, Comgenix, and Boom-Comm. He has received lecture fees from France Foundation, NACE, MedEd, Potomac, fb Communications, Pfizer, Vox Medic, the American Lung Association, WebMD, epocrates and HIT Global. He has received royalities from Associates in Medical Marketing, and Castle Connolly. He has received sponsored grants from the NIH. His institution has received sponsored grants from BI.

Funding Information:
All authors participated in study design, study enrollment procedures, review of data and manuscript preparation; drafted or revised the article for intellectual content; and provided final approval of the version to be published. Dr. Woodruff takes primary responsibility for the over-all manuscript. The COPD Clinical Research Network is supported by a Cooperative Agreement from the Division of Lung Diseases of the National Heart, Lung, and Blood Institute. At some sites General Clinical Research Centers (GCRC) were utilized; their M01 grants from the National Center for Research Resources are listed. Members of this Network, with their personnel and grant support are: Brigham and Women’s Hospital (Affiliated Sites: Fal-lon Clinic, VA Boston Healthcare System) – J.J. Reilly, Jr, (PI), G.R. Washko (Co-PI), M.L. Moy (Investigator), S. Pe-terson, C. Mayo, A. McDonald, K. Allain, K. Matthess, V. Danilack (Coordinators). Grant HL074428, GCRC Grant RR02635. Denver Health Medical Center (Affiliated Sites: National Jewish Medical & Research Center, University of Colorado) – R.K. Albert (PI), B. Make (Co-PI), M. Schwarz, C.Welsh (Investigators), M. Gilmartin, C.Verano, J. Binford (Coordinators). Grant HL074409, GCRC Grant RR00051. Los Angeles Biomedical Research Institute at Harbor-UCLA


  • Acute exacerbation of COPD (AECOPD)
  • Chronic Obstructive Pulmonary Disease (COPD)
  • Clinical trial
  • Leukotrienes
  • Zileuton


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