Hepatic Monitoring for Pazopanib

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01449825
First received: October 6, 2011
Last updated: February 21, 2013
Last verified: February 2013

October 6, 2011
February 21, 2013
December 2010
December 2014   (final data collection date for primary outcome measure)
  • Prescriber compliance with pazopanib label guidelines for liver monitoring [ Time Frame: Over four years of treatment with pazopanib ] [ Designated as safety issue: Yes ]
    Prescriber compliance with pazopanib label guidelines for liver monitoring
  • Incidence of liver enzyme elevations including combination liver enzyme elevations suggestive of Hy's Law [ Time Frame: Over four years of treatment with pazopanib ] [ Designated as safety issue: Yes ]
    Incidence of liver enzyme elevations including combination liver enzyme elevations suggestive of Hy's Law
  • Incidence of acute liver failure (ALF) [ Time Frame: Over four years of treatment with pazopanib ] [ Designated as safety issue: Yes ]
    Incidence of ALF
Same as current
Complete list of historical versions of study NCT01449825 on ClinicalTrials.gov Archive Site
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Hepatic Monitoring for Pazopanib
Postmarketing Hepatic Monitoring for Pazopanib Using Observational Databases

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.

Not Provided
Observational
Observational Model: Cohort
Time Perspective: Retrospective
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Non-Probability Sample

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.

Carcinoma, Renal Cell
  • Drug: Pazopanib use
    Treatment with pazopanib
  • Drug: Use of sunitinib, bevacizumab, or sorafenib
    Treatment with any of the three other marketed anti-VEGF drugs: sunitinib, bevacizumab, and sorafenib
  • Prescriber compliance group
    Adult (18+ years) new users of pazopanib with an indication of RCC evaluated for prescriber compliance
    Intervention: Drug: Pazopanib use
  • Incidence of liver chemistry test (LCT) elevation group
    Adult (18+ years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib in monotherapy who have a baseline LCT evaluated for LCT elevations
    Interventions:
    • Drug: Pazopanib use
    • Drug: Use of sunitinib, bevacizumab, or sorafenib
  • Incidence of drug induced liver injury (DILI) cases group
    Adult (18+ years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib with RCC (as defined by ICD-9 codes) longitudinally followed up in order to capture occurrences of LCT elevations consistent with Hy's Law to evaluate for drug-induced liver injury
    Interventions:
    • Drug: Pazopanib use
    • Drug: Use of sunitinib, bevacizumab, or sorafenib
  • Incidence of cases of ALF group
    Adult (18+ years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib with RCC (as defined by ICD-9 codes) longitudinally followed up in order to capture occurrences of ICD-9 codes indicative of possible ALF to evaluate for drug-induced liver injury
    Interventions:
    • Drug: Pazopanib use
    • Drug: Use of sunitinib, bevacizumab, or sorafenib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
1
December 2014
December 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
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NCT01449825
114430, WEUKSTV4601
No
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP