Rechallenge, Potential Drug Induced Liver Injury (Kaiser)

GlaxoSmithKline (GSK)

Status: Completed

Conditions: Drug-induced Liver Injury

Treatments: Drug: Prescription drugs with known hepatotoxicity

Study type: Observational

Funder types: Industry

Identifiers

NCT01584765

WEUKBRE5538 (Other Identifier)

115983

Details and patient eligibility

About

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.

Enrollment: 1 patient

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

1 participants in 2 patient groups

Rechallenge

Description:

positive, negative, indeterminate and intermediate rechallenge subtypes

Treatment:

Drug: Prescription drugs with known hepatotoxicity

Severe positive rechallenge

Description:

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

Treatment:

Drug: Prescription drugs with known hepatotoxicity