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Risk of Acute Liver Injury in Users of Antimicrobials

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01434173
First Posted: September 14, 2011
Last Update Posted: July 8, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
RTI Health Solutions
Information provided by (Responsible Party):
Bayer
  Purpose

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.


Condition Intervention
Drug-Induced Liver Injury Drug: Moxifloxacin (Avelox, BAY12-8039) Drug: Amoxicillin, Amoxicillin plus clavulanic acid, Cefuroxime, Clarithromycin, Doxycycline, Levofloxacin, Telithromycin

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Risk of Acute Liver Injury in Users of Antimicrobials in the HealthCore Integrated Research Database Population

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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) ]
  • 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) ]

Secondary Outcome Measures:
  • 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) ]
  • 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) ]
  • 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) ]

Enrollment: 1299056
Study Start Date: July 2001
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

Detailed Description:
Study design is called 'Cohort study with nested case-control analysis"
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01434173


Locations
United States, Delaware
Many Locations, Delaware, United States
Sponsors and Collaborators
Bayer
RTI Health Solutions
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01434173     History of Changes
Other Study ID Numbers: 14705
First Submitted: July 8, 2011
First Posted: September 14, 2011
Last Update Posted: July 8, 2014
Last Verified: July 2014

Keywords provided by Bayer:
Liver Diseases
Anti-Bacterial Agents
Fluoroquinolones
Amoxicillin
Amoxicillin-Potassium Clavulanate Combination
Clarithromycin
Doxycycline
Cefuroxime
Case-Control Studies
Retrospective Studies
Cohort Studies
Epidemiologic Research Design
Epidemiologic Studies
HealthCore Integrated Research Database (non-MESH)
United States
Human
Insurance Claim Review

Additional relevant MeSH terms:
Wounds and Injuries
Chemical and Drug Induced Liver Injury
Liver Diseases
Digestive System Diseases
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Poisoning
Amoxicillin
Moxifloxacin
Clarithromycin
Doxycycline
Anti-Bacterial Agents
Levofloxacin
Ofloxacin
Clavulanic Acids
Clavulanic Acid
Cefuroxime
Cefuroxime axetil
Telithromycin
Amoxicillin-Potassium Clavulanate Combination
Anti-Infective Agents
Norgestimate, ethinyl estradiol drug combination
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female