Clinical Trial: Rechallenge, Potential Drug Induced Liver Injury (Kaiser)

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

Official Title: Rechallenge Analysis: Detection of Potential Drug-Induced Liver Injury Using Kaiser California Database

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.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome: Liver injury rechallenge [ Time Frame: Up to seven and a half years ]

Liver injury in relation to rechallenge types (positive, negative, indeterminate and intermediate) for hepatocellular, cholestatic and mixed DILI, respectively, defined according to Danan & Benichou, 1993, J Clin Epidemiol, 46(11): p. 1323-30.


Original Primary Outcome: Same as current

Current Secondary Outcome: Severe positive rechallenge [ Time Frame: Up to seven and a half years ]

Severe positive rechallenge, 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<26 weeks in the absence of underlying cirrhosis; other organ failure considered due to DILI; or liver-related hospitalization. In subjects not meeting the definition of chronic liver injury and exhibiting persistent ALT≥3xULN or AP or bilirubin ≥2xULN after initial injury, positive drug rechallenge is defined as a doubling of ALT, alkaline phosphatase or bilirubin.


Original Secondary Outcome: Same as current

Information By: GlaxoSmithKline

Dates:
Date Received: April 12, 2012
Date Started: February 2012
Date Completion:
Last Updated: July 3, 2014
Last Verified: July 2014