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

Phase 3
Terminated
Conditions
Pulmonary Disease, Chronic Obstructive
Interventions
Drug: Placebo
Registration Number
NCT00493974
Lead Sponsor
University of Minnesota
Brief Summary

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.

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
119
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo
ZileutonZileutonZileuton (Zyflo, 600 mg 4 times a day)
Primary Outcome Measures
NameTimeMethod
Length of Hospital StayMeasured at Day 30

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.

Secondary Outcome Measures
NameTimeMethod
Change in FEV1% PredictedMeasured at Baseline and Day 30

Change in Post-bronchodilator FEV1% predicted comparing data at 30 day visit with baseline.

Change in FEV1/FEV6 Levelsfrom baseline to day of discharge

Change in Post-bronchodilator FEV1/FEV6 ratio comparing data at discharge visit with baseline.

Treatment FailureBaseline to day 30 visit

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.

Health-related Quality of LifeChange from Baseline and 1 Month

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 in Urinary Leukotriene (LTE4) LevelsBaseline and 72 hours later

Change in natural log-transformed LTE4 (ng/mg Cr.) from Baseline to 72 Hours

Trial Locations

Locations (14)

University of Pittsburgh Emphysema Research Center

🇺🇸

Pittsburgh, Pennsylvania, United States

HealthPartners Research Foundation

🇺🇸

Minneapolis, Minnesota, United States

University of California San Francisco-Airway Clinical Research Center

🇺🇸

San Francisco, California, United States

LA BioMed at Harbor, University of California

🇺🇸

Los Angeles, California, United States

Veteran's Administration Medical Center

🇺🇸

Minneapolis, Minnesota, United States

Denver Health Medical Center

🇺🇸

Denver, Colorado, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

University of Alabama Lung Health Center

🇺🇸

Birmingham, Alabama, United States

University of Maryland Hospital

🇺🇸

Baltimore, Maryland, United States

National Jewish Medical and Research Center

🇺🇸

Denver, Colorado, United States

Temple University Lung Center

🇺🇸

Philadelphia, Pennsylvania, United States

Fallon Clinic

🇺🇸

Boston, Massachusetts, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

University of Michigan Medical Center

🇺🇸

Ann Arbor, Michigan, United States

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