Hepatotoxicity Related to Protein Kinase Inhibitors

Hepatotoxicity Related to Protein Kinase Inhibitors in Cancer Patients : an Observational and Retrospective Study Using the FDA Adverse Event Reporting System (FAERS)

Although protein kinase inhibitors (PKIs) have proved effective in treating many cancers, few patients receiving PKIs may experience rare but life-threatening hepatotoxicity such as hepatic failure. Today, there is no large-scale retrospective pharmacovigilance study focusing on protein kinase inhibitors-related hepatotoxicity.

The objective was to investigate reports of hepatotoxicity related to protein kinase inhibitors using FDA Adverse Event Reporting System (FAERS).

Study Overview

• Status: Recruiting
• Conditions: Cancer
• Intervention / Treatment: Drug: Protein Kinase Inhibitor

Detailed Description

The investigators plan to include FDA approved PKIs from PKIDB, a curated, annotated and updated database of protein kinase inhibitors (https://www.icoa.fr/pkidb/).

The search terms of hepatotoxicities will be extracted from "Drug related hepatic disorders-comprehensive search (SMQ)" in MedDRA (Medical Dictionary for Regulatory Activities).

• Study Type: Observational
• Enrollment (Anticipated): 600000

Contacts and Locations

• Study Contact: Name: Miao Yan, PhD; Phone Number: +8615708460624; Email: yanmiao@csu.edu.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410000
      • Recruiting
      • Central South University
      • Contact: Miao Yan; Phone Number: +8615708460624; Email: yanmiao@csu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Cancer patients treated with protein kinase inhibitors and experiencing hepatotoxicities.

Description

Inclusion Criteria:

• Case reported in the FAERS database of individual safety case reports at the time of the extraction,
• Patients treated with at least 1 PKIs.

Exclusion Criteria:

• Chronology not compatible between the PKIs and hepatotoxicities

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatotoxicities cases reports related to PKIs (from FAERS database).	The investigators plan to identify number of cases of hepatotoxicities (especially severe toxicities such as hepatic failure) reports related to PKIs reported in the FAERS database by using reporting odds ratios (ROR) and information component (IC), two common method in disproportionality analysis. Clinical features such as gender, age and indications will be displayed, too.	From 2004 to Sep, 2021

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of the time to onset of hepatotoxicities after PKIs exposure.	The investigators plan to conduct a time to onset analysis of PKIs-related hepatotoxicities using weibull distribution	From 2004 to Sep, 2021
Description of the fatality cases.	Fatality cases of PKIs-related hepatotocities will be described.	From 2004 to Sep, 2021

Collaborators and Investigators

• Sponsor: Central South University

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2022
• Primary Completion (Anticipated): July 20, 2022
• Study Completion (Anticipated): August 10, 2022

Study Registration Dates

• First Submitted: June 19, 2022
• First Submitted That Met QC Criteria: June 19, 2022
• First Posted (Actual): June 24, 2022

Study Record Updates

• Last Update Posted (Actual): June 28, 2022
• Last Update Submitted That Met QC Criteria: June 23, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors
• Other Study ID Numbers: CSU20220619

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No