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 journalArticle

22 Citations (Scopus)

Abstract

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
Volume8
Issue number1
DOIs
StatePublished - Feb 2011

Fingerprint

zileuton
Chronic Obstructive Pulmonary Disease
Hospitalization
Placebos
Length of Stay
Leukotrienes
Leukotriene E4
Treatment Failure
Therapeutics
Lipoxygenase Inhibitors
Double-Blind Method
Sample Size
Creatinine
Biomarkers
Outcome Assessment (Health Care)

Keywords

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

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Woodruff, P. G., Albert, R. K., Bailey, W. C., Casaburi, R., Connett, J. E., Cooper, J. A. D., ... Lazarus, S. C. (2011). Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization. COPD: Journal of Chronic Obstructive Pulmonary Disease, 8(1), 21-29. https://doi.org/10.3109/15412555.2010.540273

Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization. / Woodruff, Prescott G.; Albert, Richard K.; Bailey, William C.; Casaburi, Richard; Connett, John E.; Cooper, John A D; Criner, Gerard J.; Curtis, Jeffrey L.; Dransfield, Mark T.; Han, Meilan K.; Harnden, Sarah M.; Kim, Victor; Marchetti, Nathaniel; Martinez, Fernando J.; McEvoy, Charlene E.; Niewoehner, Dennis E.; Reilly, John J.; Rice, Kathryn; Scanlon, Paul D; Scharf, Steven M.; Sciurba, Frank C.; Washko, George R.; Lazarus, Stephen C.

In: COPD: Journal of Chronic Obstructive Pulmonary Disease, Vol. 8, No. 1, 02.2011, p. 21-29.

Research output: Contribution to journalArticle

Woodruff, PG, Albert, RK, Bailey, WC, Casaburi, R, Connett, JE, Cooper, JAD, 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 2011, 'Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization', COPD: Journal of Chronic Obstructive Pulmonary Disease, vol. 8, no. 1, pp. 21-29. https://doi.org/10.3109/15412555.2010.540273
Woodruff, Prescott G. ; Albert, Richard K. ; Bailey, William C. ; Casaburi, Richard ; Connett, John E. ; Cooper, John A D ; Criner, Gerard J. ; Curtis, Jeffrey L. ; Dransfield, Mark T. ; Han, Meilan K. ; Harnden, Sarah M. ; Kim, Victor ; Marchetti, Nathaniel ; Martinez, Fernando J. ; McEvoy, Charlene E. ; Niewoehner, Dennis E. ; Reilly, John J. ; Rice, Kathryn ; Scanlon, Paul D ; Scharf, Steven M. ; Sciurba, Frank C. ; Washko, George R. ; Lazarus, Stephen C. / Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization. In: COPD: Journal of Chronic Obstructive Pulmonary Disease. 2011 ; Vol. 8, No. 1. pp. 21-29.
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AU - Woodruff, Prescott G.

AU - Albert, Richard K.

AU - Bailey, William C.

AU - Casaburi, Richard

AU - Connett, John E.

AU - Cooper, John A D

AU - Criner, Gerard J.

AU - Curtis, Jeffrey L.

AU - Dransfield, Mark T.

AU - Han, Meilan K.

AU - Harnden, Sarah M.

AU - Kim, Victor

AU - Marchetti, Nathaniel

AU - Martinez, Fernando J.

AU - McEvoy, Charlene E.

AU - Niewoehner, Dennis E.

AU - Reilly, John J.

AU - Rice, Kathryn

AU - Scanlon, Paul D

AU - Scharf, Steven M.

AU - Sciurba, Frank C.

AU - Washko, George R.

AU - Lazarus, Stephen C.

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N2 - 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.

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