Risk of Acute Liver Injury in Users of Antimicrobials

July 7, 2014 updated by: Bayer

Risk of Acute Liver Injury in Users of Antimicrobials in the HealthCore Integrated Research Database Population

Moxifloxacin is a broad-spectrum antibacterial agent used to treat common community-acquired respiratory tract infections, complicated intra-abdominal infections, and pelvic inflammatory disease. In the clinical development program, moxifloxacin was associated with some hepatic adverse drug reactions. To evaluate further the hepatic safety profile of moxifloxacin, a retrospective cohort study with nested case-control analysis will be conducted to assess the rate of noninfectious acute liver injury among new users of moxifloxacin and of other antimicrobials prescribed for similar indications, including amoxicillin, amoxicillin plus clavulanic acid, cefuroxime, clarithromycin, doxycycline, levofloxacin, and telithromycin.

The study will be implemented in the population included in the HealthCore Integrated Research Database (HIRD). Eligible patients are adults aged 18 years and older with continuous enrollment in the HIRD for at least 6 months before their first claim for a prescription for a study antimicrobial. Follow-up will start at the date of the first prescription until the date of the earliest of the following events: noninfectious acute liver injury, occurrence of an exclusion criterion, end of study period, disenrollment from database, or death. Patients with chronic alcoholism or cirrhosis, infectious hepatitis, HIV/AIDS, or pregnant women will not be included.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study design is called 'Cohort study with nested case-control analysis"

Study Type

Observational

Enrollment (Actual)

1299056

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The source of study cohort will be the HealthCore Integrated Research DatabaseTM (HIRD) population, which comprises a broad, clinically rich and geographically diverse spectrum of longitudinal claims data from health plans in the United States of America (US)

Description

Inclusion Criteria:

  • All persons meeting the following criteria during the study period (July 1, 2001, through March 31, 2009) are eligible for study inclusion:
  • First insurance claim for a dispensing of one of the study antimicrobials during the study period ("new users")
  • Aged 18 years old or older
  • Continuous enrollment in the study database for at least 6 months prior to start of follow-up (which is the date of the first claim for any of the study antimicrobials)
  • Patient data defined as acceptable for research purposes according to the quality criteria of the HIRD

Exclusion Criteria:

  • Pregnant women
  • Patients with chronic alcoholism or cirrhosis
  • Patients with history of acute and/or chronic infectious hepatitis or HIV/AIDS

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group 1
Drug: Moxifloxacin (Avelox, BAY12-8039)
Eligible patients who are new users of moxifloxacin during the study period. A new user is defined as a person who has a first recorded dispensing of moxifloxacin during the study period and who has not had a previous recorded dispensing for any of the study antimicrobials during the previous 180 days
Group 2
Drug: Amoxicillin, Amoxicillin plus clavulanic acid, Cefuroxime, Clarithromycin, Doxycycline, Levofloxacin, Telithromycin
Eligible patients who are new users of one of the other study antimicrobials (amoxicillin, amoxicillin plus clavulanic acid, cefuroxime, clarithromycin, doxycycline, levofloxacin, or telithromycin) during the study period. A new user is defined as a person who has a first recorded dispensing of a study a study antimicrobial during the study period and who has not had a previous recorded dispensing for any of the study antimicrobials during the previous 180 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence ratio of noninfectious acute liver injury fulfilling the International Consensus Meeting criteria for drug-induced liver disorders in the study population during periods of treatment with each of the study antimicrobials and nonuse
Time Frame: From the first day of full exposure of a study antimicrobial (day after the date of dispensing) to the end of follow-up (up to 8 years)
From the first day of full exposure of a study antimicrobial (day after the date of dispensing) to the end of follow-up (up to 8 years)
Incidence rate ratio of noninfectious acute liver injury fulfilling the International Consensus Meeting criteria for drug-induced liver disorders during treatment with each of the study antimicrobials compared to that during of nonuse
Time Frame: From the first day of full exposure of a study antimicrobial (day after the date of dispensing) to the end of follow-up (up to 8 years)
From the first day of full exposure of a study antimicrobial (day after the date of dispensing) to the end of follow-up (up to 8 years)

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence rate and incidence rate ratio of noninfectious severe hepatocellular injury as defined by the Hy's Law criteria modified by the FDA Working Group (FDA Working group, 2000; Temple, 2006; Navarro and Senior, 2006)
Time Frame: From the first day of full exposure of a study antimicrobial (day after the date of dispensing) to the end of follow-up (up to 8 years)
From the first day of full exposure of a study antimicrobial (day after the date of dispensing) to the end of follow-up (up to 8 years)
Incidence rate and incidence rate ratio of noninfectious acute liver failure, defined as acute liver injury with evidence of coagulation abnormality and any degree of mental alteration (encephalopathy) (Polson and Lee, 2005)
Time Frame: From the first day of full exposure of a study antimicrobial (day after the date of dispensing) to the end of follow-up (up to 8 years)
From the first day of full exposure of a study antimicrobial (day after the date of dispensing) to the end of follow-up (up to 8 years)
Cumulative incidence of noninfections acute liver injury, noninfectious severe hepatocellular injury, and noninfectious acute liver failure at weekly intervals after the start of first episode of treatment with each of the study antimicrobials
Time Frame: From the first day of full exposure of a study antimicrobial (day after the date of dispensing) to the end of follow-up (up to 8 years)
From the first day of full exposure of a study antimicrobial (day after the date of dispensing) to the end of follow-up (up to 8 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bayer

Collaborators

RTI Health Solutions

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2001

Primary Completion (ACTUAL)

March 1, 2009

Study Completion (ACTUAL)

March 1, 2009

Study Registration Dates

First Submitted

July 8, 2011

First Submitted That Met QC Criteria

September 13, 2011

First Posted (ESTIMATE)

September 14, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

July 8, 2014

Last Update Submitted That Met QC Criteria

July 7, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14705

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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