TARGET-EU: Tolvaptan and risk associated to hepatotoxicity in autosomal dominant polycystic kidney disease

20/05/2026
20/05/2026
EU PAS number:
EUPAS1000001005
Study
Ongoing
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Study summary
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Study identification

EU PAS number

EUPAS1000001005

Study ID

1000001005

Official title and acronym

TARGET-EU: Tolvaptan and risk associated to hepatotoxicity in autosomal dominant polycystic kidney disease

DARWIN EU® study

No

Study countries

Netherlands
Spain
United Kingdom

Study description

This case study is part of the broader TARGET EU project (EUPAS1000000539), which aims to advance the regulatory use of real-world data through the application of target trial emulation and estimand methodologies.

Background: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a chronic, inherited systemic disorder with manifestations that occur mainly renally, but also in other organs. Tolvaptan is the only approved drug for treatment of ADPKD in adults who are at risk of a rapidly progressive phenotype. Tolvaptan is a vasopressin V2 receptor agonist that blocks vasopressin signalling, which is an important driver of kidney cyst growth in ADPKD. A potentially serious side effect of tolvaptan is hepatotoxicity. In several clinical trials the risk of hepatotoxicity has been reported, and special warnings and safety measures have been included in the label.

Objectives: The current study aims to investigate the safety of tolvaptan use through assessing the risk of hepatotoxicity associated with tolvaptan treatment in ADPKD patients compared to the risk in patients who are unexposed to tolvaptan.

Methods: We will conduct a cohort study with a prevalent new-user design using linked electronic health records from the UK (CPRD) from 2015 until the latest available data. Eligible individuals are adults (≥ 18 years) with ADPKD who, for the intervention group, initiated tolvaptan treatment since market authorisation or, for the control group, who had a time-matched visit to a physician without a tolvaptan prescription. In the primary estimand, a treatment policy strategy is used for treatment discontinuation, a hypothetical strategy is used for tolvaptan initiation in the control group or the use of medication with hepatotoxic effects, and a while alive strategy is used for all-cause mortality. The primary analysis uses a Cox proportional hazards model, with supplemental analyses using an accelerated failure time model to estimate restricted mean survival time(RMST).

Study status

Ongoing
Research institutions and networks

Institutions

Teamit Institute
Spain
First published:
12/03/2024
Institution Other ENCePP partner

Networks

Contact details

Maarten Lambert 0000-0003-4958-9920

Primary lead investigator
ORCID number:
0000-0003-4958-9920

Study timelines

Date when funding contract was signed

Actual:

Study start date

Actual:

Date of final study report

Planned:
Sources of funding
EMA
Regulatory

Was the study required by a regulatory body?

No

Is the study required by a Risk Management Plan (RMP)?

Not applicable