Clinical trial NCT01449825: Hepatic Monitoring for Pazopanib
Official title: Postmarketing Hepatic Monitoring for Pazopanib Using Observational Databases
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Carcinoma, Renal Cell
Keywords: hepatic safety
prescriber compliance
pazopanib
epidemiology
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-10-10
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population consists of adult (18+years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib.

Two U.S. healthcare databases and one Dutch-linked medical registry system will contribute de-identified and anonymised data from electronic medical records to the surveillance program.

Brief summary: Pazopanib is approved by the FDA and EMA as targeted therapy for the indication of advanced renal cell carcinoma (RCC). Hepatic safety events were observed in the pazopanib pivotal clinical trial and the U.S. pazopanib label information contains a 'black box warning' regarding hepatotoxicity. These clinical observations have prompted GSK to undertake a proactive pharmacovigilance strategy focused on hepatic safety that goes beyond spontaneous reporting of adverse events.

The goals of the study are to assess prescriber compliance with pazopanib label guidelines for liver monitoring among patients with RCC, as well as to quantify and characterize the hepatic safety profile of the product in real-world clinical practice compared to other anti-vascular endothelial growth factor (anti-VEGF) drugs. As part of regulatory commitments, GSK will conduct parallel epidemiologic analyses in different patient populations as represented in multiple databases of electronic medical records. To enhance accrual of data, GSK will conduct this safety surveillance program simultaneously across datasets in order to detect and characterize all cases of liver enzyme elevations in diverse populations of patients receiving pazopanib. Two additional goals of this study are to evaluate the incidence of cases of combinations of liver enzyme elevations indicative of Hy's Law and drug-induced acute liver failure among users of pazopanib compared to users of other anti-VEGF drugs. This research effort will be coordinated by an external coordinating center.

An epidemiologic cohort study design, nested in several databases of electronic medical information, will be employed for the research questions. Following the availability of pazopanib in the relevant medical care system, the study will collect retrospective data at regular intervals over the course of four years among persons exposed to pazopanib and other anti-VEGF agents. Each patient will be characterized based on additional available information in the database (e.g., demographics, concomitant medications). Elevations in liver enzymes will be identified through laboratory data captured in these databases. Potential Hy's Law and acute liver failure cases will be identified through established screening criteria, and screen-positive cases will be reviewed by an adjudication committee of hepatologists for final determination of drug-associated causality.


Eligibility criteria: Inclusion Criteria:

* In the prescriber compliance analysis, all adult (18+ years) new users of pazopanib with an indication of RCC will be eligible for the analysis.
* In the liver enzyme elevation analysis, all adult (18+ years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib in monotherapy for any cancer type who have a baseline liver enzyme value will be eligible for the analysis.
* In the drug-induced liver injury analyses, all adult (18+ years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib with RCC (as defined by ICD-9 codes) will be longitudinally followed up in order to capture occurrences of liver enzyme elevations consistent with Hy's Law and ICD-9 codes indicative of possible ALF to evaluate for drug-induced liver injury.

Exclusion Criteria:

* N/A

Primary outcomes:
measure: Prescriber compliance with pazopanib label guidelines for liver monitoring
timeFrame: Over four years of treatment with pazopanib
measure: Incidence of liver enzyme elevations including combination liver enzyme elevations suggestive of Hy's Law
timeFrame: Over four years of treatment with pazopanib
measure: Incidence of acute liver failure (ALF)
timeFrame: Over four years of treatment with pazopanib
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: