Browse EPPT > UAZ2013-02-01
Clinical Study of the Effect of Combined Treatment of Aspirin and Zileuton on Biomarkers of Tobacco-Related Carcinogenesis in Current Smokers

The following datasets contain the data available for EPPT UAZ2013-02-01. The description and documentation for each file is listed below. SAS7bdat and CSV versions of the actual data will be available to CDAS projects approved to use this study's data.

Analysis Datasets

Files	Description
Data Dictionary (PDF - 1.2 MB)	1. The Enhanced Person dataset contains all relevant information from every dataset received (except ae dataset). Each record represents one participant and contains updated variable names, formats, and labels. All information coming from non-person-based datasets has been converted into a person-based format.
Data Dictionary (PDF - 57.8 KB)	2. The Adverse Events dataset contains adverse event information, including onset date, grade of severity, attribution to the study agent, and outcome. This version of the dataset includes updated variable names, formats, and labels.

Raw Datasets

These 23 datasets contain the raw form data received, excluding PII.

Show these datasets

Files	Description
Data Dictionary (PDF - 63.8 KB)	1. The Adverse Events dataset contains adverse events that occurred during the study.
Data Dictionary (PDF - 46.5 KB)	2. The Agent Interruption dataset contains any interruptions of the study agent during the study.
Data Dictionary (PDF - 37.2 KB)	3. The Biomarkers dataset contains PGEM and LTE4 values for the participant obtained from nasal brushing.
Data Dictionary (PDF - 48.4 KB)	4. The Blood Chemistry dataset contains results of blood tests and whether or not they were abnormal/out of range.
Data Dictionary (PDF - 42.5 KB)	5. The Comments dataset contains any comments that could not fit on forms.
Data Dictionary (PDF - 51.0 KB)	6. The Compliance dataset contains information indicating whether participants were compliant with the study protocol since the last visit.
Data Dictionary (PDF - 46.0 KB)	7. The Concomitant Medications dataset contains any concomitant medications taken throughout the study.
Data Dictionary (PDF - 43.6 KB)	8. The Death Report dataset contains participant deaths that occurred during the study. *The 1 observation contains only missing values. There were no deaths during the study.
Data Dictionary (PDF - 48.2 KB)	9. The Demographics dataset contains demographic and eligibility information.
Data Dictionary (PDF - 47.0 KB)	10. The Hematology dataset contains results of hematology tests and whether or not they were abnormal/out of range.
Data Dictionary (PDF - 45.6 KB)	11. The Intervention Administration dataset contains amounts of agent administered, returned, etc. at each visit.
Data Dictionary (PDF - 45.7 KB)	12. The Medical/Surgical History dataset contains medical/surgical history.
Data Dictionary (PDF - 43.0 KB)	13. The Medical/Surgical History Continued dataset contains medical/surgical history (continued).
Data Dictionary (PDF - 47.0 KB)	14. The Off Study dataset contains reason off study.
Data Dictionary (PDF - 47.4 KB)	15. The Other Lab Tests dataset contains results of other lab tests and whether or not they were abnormal/out of range.
Data Dictionary (PDF - 56.0 KB)	16. The Outcome Of Pregnancy dataset contains outcome of any pregnancies during the study. * The 1 observation contains only missing values. There were no pregnancies during the study.
Data Dictionary (PDF - 57.6 KB)	17. The Physical Exam dataset contains anthropometry information.
Data Dictionary (PDF - 44.8 KB)	18. The Pregnancy Specimen Data dataset contains results of pregnancy tests.
Data Dictionary (PDF - 45.4 KB)	19. The Randomization dataset contains randomization information.
Data Dictionary (PDF - 55.3 KB)	20. The Registration dataset contains demographic and eligibility information.
Data Dictionary (PDF - 51.5 KB)	21. The Scores dataset contains gene signature values for the participant obtained from nasal brushing.
Data Dictionary (PDF - 43.0 KB)	22. The Tobacco Alcohol Assessment dataset contains cigarette and alcohol history (used to determine study eligibility).
Data Dictionary (PDF - 40.9 KB)	23. The Verification dataset contains investigator verification.

Trial Summary

This randomized, double-blinded phase II trial studies the safety and effects of acetylsalicylic acid (aspirin) and Zileuton taken together on biomarkers of tobacco-related carcinogenesis in nasal tissue of current smokers. The change (if any) in biomarkers is to be evaluated.

Randomized trial with two arms:

• Arm I: 1:1 to ASA 81 mg QD + zileuton (ZyfloCR) 2x600 mg BID.
• Arm II: Matched Placebos BID.

Target Randomizable Enrollment: 44

Statistical Analysis

A two-sided two-sample t test was used to test whether or not there are significant differences in changes in gene signature scores (changes from baseline) between the treatment and placebo groups. A two-sided two-sample t test was also used to compare the baseline values of gene signature scores between the intervention arms and the baseline values of PGEM and LTE4 and changes in PGEM and LTE4 levels between the intervention arms. A two-sided paired t test was performed to evaluate the changes in gene signature scores, PGEM and LTE4 overall, by intervention arm, and by gender. All of the secondary analyses are considered exploratory so no correction for multiple comparisons were used. The Fisher's exact test was used to compare the frequency of adverse events between the intervention arms.

Enrollment Statistics

Actual Registration: 123

• 63 people randomized(63 of 123 registered)
  • 31 in Arm I: ASA+Zileuton (31 of 63 randomized)
    • 21 participants completed study
    • 21 participants completed study
      • 1 due to adverse event
      • 6 lost to follow-up
      • 2 withdrew from study
      • 1 for other reasons
  • 32 in Arm II: Placebo (32 of 63 randomized)
    • 22 participants completed study
    • 10 participants did not complete study
      • 1 due to adverse event
      • 5 lost to follow-up
      • 4 withdrew from study
• 60 people not eligible and not randomized (60 of 123 registered)

Final Analysis Population: 63

Eligibility Criteria

Inclusion Criteria

• Current tobacco smokers with ≥ 20 pack years of self-reported smoking exposure and an average use of ≥ 10 cigarettes/day
• Karnofsky ≥ 70%
• Leukocytes ≥ 3,000/microliter
• Absolute neutrophil count ≥ 1,500/microliter
• Hematocrit ≥ the lower institutional limit
• Platelets ≥ the lower institutional limits
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) within normal institutional limits
• Creatinine ≤ the upper institutional limits
• Prothrombin time (PT)/partial thromboplastin time (PTT) within normal institutional limits
• Fertile subjects must use adequate contraception (abstinence, barrier methods, or birth control pills) prior to study entry and for the duration of study participation; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Participants may have a history of indeterminate pulmonary nodule(s) by chest imaging if nodule follow-up has been completed or the study procedures would not interfere with nodule follow-up
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• History of allergic reaction to aspirin or attributed to compounds of similar chemical or biologic composition to aspirin, including other nonsteroidal anti-inflammatory drugs (NSAIDs)
• Gastric intolerance attributable to ASA or NSAIDs
• History of gastric ulcer within the past 5 years (with or without bleeding)
• Use of ASA or NSAIDs for more than 5 days per month within 3 months of enrollment
• Not willing or are unable to refrain from use of any non-study ASA, NSAIDs and leukotriene antagonists during the study period
• Adult asthma
• Chronic, current or recent (within the past three months) use of leukotriene antagonists
• Require chronic anticoagulation or anti-platelet therapy
• History of bleeding disorder or hemorrhagic stroke
• Chronic, current or recent (within the past three months) use of glucocorticoids (systemic, topical and/or nasal sprays or steroid topical creams to large body surface area); use of steroid topical creams for small body areas (≤ 10% body surface) during study intervention is allowed
• History of chronic sinusitis or recent nasal polyps
• History of, or current, active or chronic liver disease even if transaminases have normalized
• History of allergic reaction to zileuton or attributed to compounds of similar chemical or biologic composition to zileuton
• Are taking drugs known to interact with zileuton, including theophylline, warfarin, and propranolol
• Not willing or are unable to limit alcohol consumption to ≤ 2 alcoholic beverages a day during the study period
• Pregnant or lactating women; breastfeeding should be discontinued if the mother is treated with aspirin; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Participants may not be receiving any other investigational agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Have a known history of inability to absorb an oral agent
• Invasive cancer within the past five years except non-melanoma skin cancer
• Urine cotinine level, if collected at screening, does not confirm active smoking status

Schema

The Schema is a timeline of the study. It indicates start/end points, visits expected, major testing to be done, and any other information that is crucial to understanding how the study was completed.

Results/Findings:

Aspirin plus zilueton had minimal effects on the modulation of the nasal or bronchial gene expression signatures of smoking, lung cancer, and COPD but favorably modulated a bronchial gene expression signature of squamous dysplasia. Aspirin plus zileuton suppressed urinary leukotriene but not prostaglandin E2, suggesting shunting through the cyclooxygenase pathway when combined with 5-lipoxygenase inhibition. Continued investigation of leukotriene inhibitors is needed to confirm these findings, understand the long-term effects on the airway epithelium, and identify the safest, optimally dosed agents.