Clinical Trial: Risk of Acute Liver Injury in Users of Antimicrobials

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

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

Brief Summary:

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.


Detailed Summary: Study design is called 'Cohort study with nested case-control analysis"
Sponsor: Bayer

Current Primary Outcome:

  • 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) ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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) ]


Original Secondary Outcome: Same as current

Information By: Bayer

Dates:
Date Received: July 8, 2011
Date Started: July 2001
Date Completion:
Last Updated: July 7, 2014
Last Verified: July 2014