Trial Outcomes & Findings for Zileuton to Treat Adults With Chronic Obstructive Pulmonary Disease (The LEUKO Study) (NCT NCT00493974)

Last Updated: 2019-11-18

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

119 participants

Primary outcome timeframe

Measured at Day 30

Results posted on

2019-11-18

Participant Flow

Participants were recruited from ER's and inpatient units from 10 main clinical sites (and their affiliated hospitals) between September 2007 and October 2008.

Participants were screened using the eligibility criteria before randomization.

Participant milestones

Participant milestones
Measure	Zileuton Zileuton (Zyflo, 600 mg 4 times a day)	Placebo Matching placebo 4 times a day
Overall Study STARTED	60	59
Overall Study COMPLETED	47	45
Overall Study NOT COMPLETED	13	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Zileuton Zileuton (Zyflo, 600 mg 4 times a day)	Placebo Matching placebo 4 times a day
Overall Study Death	1	2
Overall Study Withdrawal by Subject	8	6
Overall Study Lost to Follow-up	4	6

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zileuton n=60 Participants Zileuton (Zyflo, 600 mg 4 times a day)	Placebo n=59 Participants Matching placebo 4 times a day	Total n=119 Participants Total of all reporting groups
Age, Continuous	62.2 years STANDARD_DEVIATION 8.2 • n=5 Participants	64.3 years STANDARD_DEVIATION 9.5 • n=7 Participants	63.2 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	18 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	41 Participants n=7 Participants	78 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	56 Participants n=5 Participants	57 Participants n=7 Participants	113 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	16 Participants n=5 Participants	24 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants	31 Participants n=7 Participants	67 Participants n=5 Participants
Race (NIH/OMB) More than one race	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Measured at Day 30

Population: Participants were analyzed following intention to treat (ITT) method. One participant randomized to Zileuton withdrew consent before hospital discharge. Days to discharge are set at a maximum of 10 days.

Outcome measures

Outcome measures
Measure	Zileuton n=59 Participants Zileuton (Zyflo, 600 mg 4 times a day)	Placebo n=59 Participants Matching placebo 4 times a day
Length of Hospital Stay	3 Days Standard Deviation 2.19	3 Days Standard Deviation 3.06

SECONDARY outcome

Timeframe: Measured at Baseline and Day 30

Population: Participants were analyzed using the intent to treat method. The N is lower than total randomized due to participants that were unable to perform spirometry at baseline.

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

Outcome measures

Outcome measures
Measure	Zileuton n=14 Participants Zileuton (Zyflo, 600 mg 4 times a day)	Placebo n=9 Participants Matching placebo 4 times a day
Change in FEV1% Predicted	6.8 percent predicted Standard Error 4.2	8.0 percent predicted Standard Error 4.4

SECONDARY outcome

Timeframe: from baseline to day of discharge

Population: Participants were analyzed using the intent to treat method. The N is lower than total randomized due to participants that were unable to perform spirometry at baseline and missing discharge data.

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

Outcome measures

Outcome measures
Measure	Zileuton n=8 Participants Zileuton (Zyflo, 600 mg 4 times a day)	Placebo n=8 Participants Matching placebo 4 times a day
Change in FEV1/FEV6 Levels	0.02 ratio Standard Error 0.03	0.03 ratio Standard Error 0.02

SECONDARY outcome

Timeframe: Baseline to day 30 visit

Population: Participants were analyzed following intention to treat (ITT) method.

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.

Outcome measures

Outcome measures
Measure	Zileuton n=60 Participants Zileuton (Zyflo, 600 mg 4 times a day)	Placebo n=59 Participants Matching placebo 4 times a day
Treatment Failure Death	1 Participants	2 Participants
Treatment Failure Intubation	1 Participants	1 Participants
Treatment Failure Hospital Readmission	7 Participants	7 Participants
Treatment Failure Urgent Visit	7 Participants	6 Participants
Treatment Failure Intensification of therapy	11 Participants	11 Participants
Treatment Failure Any Treatment Failure	14 Participants	16 Participants

SECONDARY outcome

Timeframe: Change from Baseline and 1 Month

Population: Participants were analyzed using the intent to treat method and included those that had SGRQ data at 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.

Outcome measures

Outcome measures
Measure	Zileuton n=46 Participants Zileuton (Zyflo, 600 mg 4 times a day)	Placebo n=43 Participants Matching placebo 4 times a day
Health-related Quality of Life	-10.6 Units on a scale Standard Deviation 14.8	-8.5 Units on a scale Standard Deviation 14.6

SECONDARY outcome

Timeframe: Baseline and 24 hours

Population: Intent to Treat. Participants with urine sample at both visits.

Change in natural log-transformed LTE4 (ng/mg Cr.) from Baseline to 24 Hours

Outcome measures

Outcome measures
Measure	Zileuton n=46 Participants Zileuton (Zyflo, 600 mg 4 times a day)	Placebo n=42 Participants Matching placebo 4 times a day
Change in Urinary Leukotriene (LTE4) Levels	-1.38 (ng/mg Cr.) Standard Error 0.17	0.14 (ng/mg Cr.) Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline and 72 hours later

Population: Intent to Treat. Participants with urine sample at both visits.

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

Outcome measures

Outcome measures
Measure	Zileuton n=22 Participants Zileuton (Zyflo, 600 mg 4 times a day)	Placebo n=20 Participants Matching placebo 4 times a day
Change in Urinary Leukotriene (LTE4) Levels	-1.32 (ng/mg Cr.) Standard Error 0.40	0.26 (ng/mg Cr.) Standard Error 0.38

Adverse Events

Zileuton

Serious events: 17 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 20 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Zileuton n=60 participants at risk Zileuton (Zyflo, 600 mg 4 times a day)	Placebo n=59 participants at risk Matching placebo 4 times a day
Respiratory, thoracic and mediastinal disorders Dyspnea	15.0% 9/60 • Number of events 19 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	10.2% 6/59 • Number of events 14 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Respiratory, thoracic and mediastinal disorders COPD worsening	6.7% 4/60 • Number of events 4 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	10.2% 6/59 • Number of events 6 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.

Additional Information

Sarah Lindberg

University of Minnesota

Phone: 612-626-9011

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Zileuton n=60 participants at risk Zileuton (Zyflo, 600 mg 4 times a day)	Placebo n=59 participants at risk Matching placebo 4 times a day
Immune system disorders Allergic Reaction( to amiodarone)	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	0.00% 0/59 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Respiratory, thoracic and mediastinal disorders COPD Exacerbation	13.3% 8/60 • Number of events 8 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	16.9% 10/59 • Number of events 10 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Skin and subcutaneous tissue disorders Cellulitis	0.00% 0/60 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	1.7% 1/59 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Musculoskeletal and connective tissue disorders Chest Pain	0.00% 0/60 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	1.7% 1/59 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Gastrointestinal disorders Colitis	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	0.00% 0/59 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Cardiac disorders Congestive Heart Failure	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	0.00% 0/59 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Psychiatric disorders Depressive disorder	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	1.7% 1/59 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Cardiac disorders Heart Failure	0.00% 0/60 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	1.7% 1/59 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Cancer	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	0.00% 0/59 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Infections and infestations MRSA bursitis	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	0.00% 0/59 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Infections and infestations Mycobacterium Avium Intracellular Complex	0.00% 0/60 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	1.7% 1/59 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Cardiac disorders Myocardial Infarction	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	0.00% 0/59 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/60 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	1.7% 1/59 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Gastrointestinal disorders Rectal bleeding	0.00% 0/60 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	1.7% 1/59 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Renal and urinary disorders Renal Mass	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	1.7% 1/59 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.7% 1/60 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	0.00% 0/59 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Vascular disorders Stroke	0.00% 0/60 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	1.7% 1/59 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.
Gastrointestinal disorders Urinary Tract Infection	0.00% 0/60 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.	1.7% 1/59 • Number of events 1 • Participants were followed for adverse events from randomization to the 30 day follow-up visit. AEs that continued past the end of the study period were followed until the Investigator believed it reached a stable clinical endpoint or resolved.