Rechallenge, Potential Drug Induced Liver Injury (Kaiser)

NCT ID: NCT01584765

Last Updated: 2014-07-08

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2013-04-30

Brief Summary

Drug re-administration or rechallenge should be avoided after drug-induced liver injury (DILI) to avoid recurrent and fatal injury. Rechallenge outcomes vary considerably by drug and patient subjects. In order to better predict these outcomes, the objective of this analysis is to assess clinical outcomes of positive drug rechallenge following possible drug-induced liver injury. Electronic medical records from Kaiser Permanente California (KPSC), a managed care organization, will be utilized to identify patients who experience possible drug-induced liver injury following exposure to medications associated with hepatotoxicity, and who are then rechallenged with the medication.

Conditions

Drug-induced Liver Injury

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Rechallenge

positive, negative, indeterminate and intermediate rechallenge subtypes

Prescription drugs with known hepatotoxicity

Intervention Type: DRUG

14 prescription drugs with known hepatotoxicity : Amoxicillin/clavulanate, nitrofurantoin, isoniazid, trimethoprim-sulfamethoxazole, duloxetine, valproate, interferon-beta, ciprofloxacin, lamotrigine, phenytoin, diclofenac, terbinafine, levofloxacin, aripiprazole

Severe positive rechallenge

Subtype of positive rechallenge is defined as: ALT≥5 xULN or AP ≥2 xULN and bilirubin ≥2 xULN with one of the following: INR ≥1.5, Ascites, or Encephalopathy where time from liver chemistry elevation to INR≥1.5,ascites, or encephalopathy is less than 26 weeks in the absence of underlying cirrhosis; other organ failure considered due to DILI; liver-related hospitalization

Prescription drugs with known hepatotoxicity

Intervention Type: DRUG

14 prescription drugs with known hepatotoxicity : Amoxicillin/clavulanate, nitrofurantoin, isoniazid, trimethoprim-sulfamethoxazole, duloxetine, valproate, interferon-beta, ciprofloxacin, lamotrigine, phenytoin, diclofenac, terbinafine, levofloxacin, aripiprazole

Interventions

Prescription drugs with known hepatotoxicity

14 prescription drugs with known hepatotoxicity : Amoxicillin/clavulanate, nitrofurantoin, isoniazid, trimethoprim-sulfamethoxazole, duloxetine, valproate, interferon-beta, ciprofloxacin, lamotrigine, phenytoin, diclofenac, terbinafine, levofloxacin, aripiprazole

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients who received at least one prescription for a suspect drug between Jan 1, 2003 and June 30, 2009 (drug initiation period)
• Patients who experienced incident DILI event (identified by ALT ≥3xULN or AP ≥2xULN within 6 months of suspect drug administration) during the first exposure period that:

1. Resolved to within normal limits of ALT (for hepatocellular & mixed) or AP (for cholestatic) within 180 days or

2. Resolved to ALT < 3xULN (for hepatocellular & mixed) within 90 days or AP<2xULN (for cholestatic) within 180 days or

3. Dropped by ≥50% of (Peak ALT - ULN) for hepatocellular or of (Peak AP - ULN) for cholestatic or mixed within 180 days

• Patients who were rechallenged with the same suspect drug; rechallenge will include first rechallenge event for the analysis.
• Patients who had at least of 12 months of continuous membership and drug benefit prior to and on the dispensing index date (inclusive). There is no minimum restriction of continuous membership plus drug benefit after the start date.
• Patients who were 18 years of age or older at the time of the first drug dispensing (index date) during the drug initiation period Jan 1, 2003 and June 30, 2009. Each patient's first prescription for the study drugs during the drug initiation period will be identified as index prescription.
• Patients who had health insurance coverage with full medical, pharmacy and lab benefits at the index date.

Exclusion Criteria

• Patients meeting the definition of chronic liver injury and exhibiting persistent ALT≥3xULN or AP or bilirubin ≥2xULN within 90 days after initial injury
• Patients with chronic liver injury diagnostic codes or included in KPSC disease registries preceding the initial or rechallenge liver injury

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Other Identifiers

WEUKBRE5538

Identifier Type: OTHER

Identifier Source: secondary_id

115983

Identifier Type: -

Identifier Source: org_study_id