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Risk of Acute Liver Injury in Users of Antimicrobials

This study has been completed.
Sponsor:
Collaborator:
RTI Health Solutions
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01434173
First received: July 8, 2011
Last updated: July 7, 2014
Last verified: July 2014
  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) ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: Yes ]

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) ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: Yes ]

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01434173     History of Changes
Other Study ID Numbers: 14705
Study First Received: July 8, 2011
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

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:
Drug-Induced Liver Injury
Chemically-Induced Disorders
Digestive System Diseases
Drug-Related Side Effects and Adverse Reactions
Liver Diseases
Poisoning
Amoxicillin
Amoxicillin-Potassium Clavulanate Combination
Anti-Infective Agents
Cefuroxime
Cefuroxime axetil
Clarithromycin
Clavulanic Acid
Clavulanic Acids
Doxycycline
Levofloxacin
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Ofloxacin
Telithromycin
Anti-Bacterial Agents
Anti-Infective Agents, Urinary
Antimalarials
Antineoplastic Agents
Antiparasitic Agents
Antiprotozoal Agents
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Combined

ClinicalTrials.gov processed this record on November 27, 2014