Zileuton to Treat Adults With Chronic Obstructive Pulmonary Disease (The LEUKO Study) (LEUKO)

Antileukotriene Therapy for COPD Exacerbations

Chronic obstructive pulmonary disease (COPD) is a long-term lung disease that is caused by cigarette smoking or by breathing in other lung irritants, including pollution, dust, or chemicals. The purpose of this study is to evaluate the effectiveness of zileuton, a medication that is used to control asthma symptoms, at reducing the length of a hospital stay for adults who are hospitalized for a COPD exacerbation, or worsening of COPD symptoms.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Zileuton; Drug: Placebo

Detailed Description

COPD is a disease in which the lung airways are partly damaged and obstructed, making it difficult to breathe. COPD is the fourth leading cause of death in the United States. Symptoms include coughing, excess mucus production, shortness of breath, wheezing, and chest tightness. Treatment usually includes inhaled bronchodilator or steroid medications that work by relaxing the muscles around the lung airways and reducing inflammation. Zileuton, a medication that is used to prevent asthma symptoms, may be beneficial in treating people who experience COPD exacerbations. Zileuton works by blocking the formation of substances that cause inflammation, fluid retention, and constriction in the lungs. The purpose of this study is to evaluate the effectiveness of zileuton at reducing the length of a hospital stay for adults who are hospitalized for a COPD exacerbation.

This study will enroll adults who are admitted to the hospital due to severe COPD symptoms. Participants will be randomly assigned to receive either zileuton or placebo four times a day for up to 14 days. While in the hospital, lung function testing and urine collection will occur. Study visits will occur at Days 14 and 30, and will include lung function testing, a medical history review, and a study drug adverse effects review.

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Veteran's Administration Medical Center
    • Birmingham, Alabama, United States, 35249
      • University of Alabama Lung Health Center
  • California
    • Los Angeles, California, United States, 90502
      • LA BioMed at Harbor, University of California
    • San Francisco, California, United States, 94143
      • University of California San Francisco-Airway Clinical Research Center
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center
    • Denver, Colorado, United States, 80206
      • National Jewish Medical and Research Center
    • Denver, Colorado, United States, 80220
      • Veteran's Administration Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02132
      • Veteran's Administration Medical Center
    • Boston, Massachusetts, United States, 01605
      • Fallon Clinic
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Veteran's Administration Medical Center
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55440
      • HealthPartners Research Foundation
    • Minneapolis, Minnesota, United States, 55417
      • Veteran's Administration Medical Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Lung Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Emphysema Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Admitted to the hospital for a COPD exacerbation
• FEV1 less than 60% of predicted level
• At least 10 pack years of smoking

Exclusion Criteria:

• Any uncontrolled systemic disease
• Known hypersensitivity to zileuton
• Asthma
• Lobar pneumonia or pulmonary edema
• Interstitial lung disease
• Medical condition that is likely to limit survival to less than 30 days at the time of study entry
• History of liver disease
• Current use of theophylline
• Participation in another clinical trial in the COPD Clinical Research Network
• Incarceration
• Institutionalization
• Pregnant
• History of a suicide attempt
• Prior inpatient admission for a psychiatric disorder
• Bipolar disorder

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo 4 x daily; Other Names: Inactive Matching Placebo
Active Comparator: Zileuton; Zileuton (Zyflo, 600 mg 4 times a day)	Drug: Zileuton; Zyflo tablets, 600 mg, 4 times a day; Other Names: Zyflo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Hospital Stay	Admission will begin at the time the subject has been admitted to an inpatient service. Length of Stay (LOS) will be recorded in days. The LOS will be based on the number of days spent in an acute medical ward or in the ICU. Subjects that are admitted and discharged in the same 24 hour period will be recorded as a LOS of 1 day, as will subjects discharged in the ensuing 24 hour period. LOS's greater than 10 days will be truncated to 10 days.	Measured at Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in FEV1% Predicted	Change in Post-bronchodilator FEV1% predicted comparing data at 30 day visit with baseline.	Measured at Baseline and Day 30
Change in FEV1/FEV6 Levels	Change in Post-bronchodilator FEV1/FEV6 ratio comparing data at discharge visit with baseline.	from baseline to day of discharge
Treatment Failure	Treatment failure is defined as death, intubation, readmission to a hospital for COPD, urgent visit to an outpatient or ED provider for symptoms of COPD or intensification of therapy [including second course of antibiotics for COPD, and second course of systemic steroids for COPD]) in the first 30 days after randomization.	Baseline to day 30 visit
Health-related Quality of Life	St. George's Respiratory Questionnaire - Total Score The SGRQ was asked with respect to the last one month as validated for acute exacerbations of COPD by Doll et al. Scale from 0 (no disability) to 100 (maximum disability). The SGRQ total score summarizes the impact of airway specific disease on overall health status. Scores range from zero (no impairment) to 100 (maximum impairment). Scores were calculated using the SGRQ scoring Algorithm.	Change from Baseline and 1 Month
Change in Urinary Leukotriene (LTE4) Levels	Change in natural log-transformed LTE4 (ng/mg Cr.) from Baseline to 24 Hours	Baseline and 24 hours
Change in Urinary Leukotriene (LTE4) Levels	Change in natural log-transformed LTE4 (ng/mg Cr.) from Baseline to 72 Hours	Baseline and 72 hours later

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Study Chair: Prescott Woodruff, MD, University of California at San Francisco

Publications and helpful links

General Publications

• 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. Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization. COPD. 2011 Feb;8(1):21-9. doi: 10.3109/15412555.2010.540273.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: June 28, 2007
• First Submitted That Met QC Criteria: June 28, 2007
• First Posted (Estimate): June 29, 2007

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: COPD; Chronic Obstructive Pulmonary Disease; Exacerbation; Length of Stay; LOS; Anti-leukotriene
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Leukotriene Antagonists; Hormone Antagonists; Lipoxygenase Inhibitors; Zileuton
• Other Study ID Numbers: 0701M00621; U10HL074424 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO