Status:

RECRUITING

Checkpoint Inhibitor-induced Liver Injury

Lead Sponsor:

University of Nottingham

Collaborating Sponsors:

Pfizer

Conditions:

Immune-Mediated Hepatitis

Eligibility:

All Genders

18+ years

Brief Summary

In this multi-center prospective observational study, the investigators plan to identify the incidence and risk factors for checkpoint inhibitor-induced liver injury and characterize biochemical, gene...

Detailed Description

Checkpoint inhibitor-induced liver injury (ChILI) is a new incompletely understood category of hepatotoxicity which is distinct from other types of drug-induced liver injury (DILI) such as direct or i...

Eligibility Criteria

Inclusion

  • Both patient groups and control group:
  • • Able to give written informed consent OR Potential participants who have developed encephalopathy related to ChILI as a response to checkpoint inhibitor therapy, who lack the capacity to give written informed consent and have a consultee (personal or nominated) - for ChILI patient group only
  • ChILI group:
  • Patients who developed checkpoint inhibitor-induced liver injury and meet the following criteria:
  • Meets one of the following analytical thresholds at enrolment (visit 1)
  • Alanine transaminase (ALT) exceeding 5 times the upper limit of normal (ULN) OR
  • ALT exceeding 3 times ULN plus bilirubin exceeding 2 times ULN OR
  • Alkaline phosphatase (ALP) exceeding 2 times ULN with accompanying elevations of gamma-glutamyl transferase in the absence of known bone metastases driving the rise in ALP level
  • Absence of other known causes of liver injury after detailed investigations
  • Patients who developed ChILI but did not meet the above criteria at enrolment or who were found to have a different cause for their liver injury after further investigations will be excluded from the analysis
  • Control group:
  • Consecutive patients with cancer who have a clinical indication to start checkpoint inhibitors. A small proportion of patients will develop ChILI following their checkpoint inhibitor treatment and will be classified as cases.

Exclusion

  • Patients who are treated with cytotoxic chemotherapy concurrently with checkpoint inhibitors.
  • On the judgment of chief investigator that the person has certain alternative explanations to the acute event (rather than ChILI).

Key Trial Info

Start Date :

October 13 2020

Trial Type :

OBSERVATIONAL

Allocation :

ESTIMATED

End Date :

December 1 2025

Estimated Enrollment :

160 Patients enrolled

Trial Details

Trial ID

NCT04476563

Start Date

October 13 2020

End Date

December 1 2025

Last Update

September 29 2025

Active Locations (1)

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1

University of Nottingham

Nottingham, United Kingdom, NG72RD