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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Antileukotriene Therapy for COPD Exacerbations

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Zileuton
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 '

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Zileuton<br>Zileuton (Zyflo, 600 mg 4 times a day) | Drug: Zileuton<br>* Zyflo tablets, 600 mg, 4 times a day<br>* Other names: Zyflo;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo 4 x daily<br>* Other names: Inactive Matching Placebo;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, COPD, Exacerbation, Anti-leukotriene, Length of Stay, LOS