Study identification

PURI

https://redirect.ema.europa.eu/resource/40864

EU PAS number

EUPAS2181

Study ID

40864

Official title and acronym

Study of Acute Liver Transplant: A study of NSAIDs-exposed acute liver failure in European transplant centres (SALT-I)

DARWIN EU® study

No

Study countries

Greece
Ireland
Italy
Netherlands
Portugal
United Kingdom

Study description

The European Medicines Agency (EMA) has expressed concern about the possibility of an increased relative frequency of acute liver failure (ALF) subsequent to nimesulide exposure. The SALT-1 study was initiated to evaluate the risk of ALF in patients exposed to non-steroidal anti-inflammatory drugs (NSAIDs) at the request of the CHMP. The protocol was approved by the CHMP in November 2008 and the final version was sent to the CHMP in December 2008. The SALT-1 study was a multicenter, multinational retrospective case-population study of patients exposed to NSAIDs registered for liver transplantation (LT) because of ALF between 01/01/2005 and 31/12/2007. Seven countries participated, France, Italy, Portugal, Greece, Ireland, Netherlands, UK. The primary objectives were to estimate the absolute frequency and population exposure of ALF leading to registration for LT in patients exposed to the different NSAIDs. Exclusively pediatric (n=4) or oncology centres (n=1) were not eligible, 57 centres were contacted. Criteria for inclusion were: adults ≥18 years of age at the time of registration on LT list with ALF, whether the LT is actually performed or not, and resident of the participating countries. Index date (ID) was the date of initial symptoms of liver disease. Exposure was considered within 90 days prior to ID. ALF cases were classified as “with identified clinical cause”, “possibly drug-exposed/no identified clinical cause" "exposed to NSAIDs" "exposed to drugs without NSAIDs" "without drug exposure and no identified clinical cause" or "acute drug intoxication". A descriptive analysis of all drug-exposed cases of ALF was performed. Per country rates of NSAID-exposed transplantation registered ALF among subjects exposed to NSAIDs within 30 days prior to the index date were estimated along with its corresponding 95% confidence interval (CI) from a Poisson distribution and expressed in cases per million treatment-years. Estimation was irrespective of any causality.

Study status

Finalised
Research institutions and networks

Institutions

RTI Health Solutions (RTI-HS)
France
Spain
Sweden
United Kingdom
United Kingdom (Northern Ireland)
United States
First published:
13/03/2025
InstitutionNot-for-profitENCePP partner

Contact details

Ezgi Gulmez

Primary lead investigator
Study timelines

Date when funding contract was signed

Planned:
Actual:

Study start date

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Data analysis start date

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Date of interim report, if expected

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Date of final study report

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Sources of funding
Pharmaceutical company and other private sector 

More details on funding

Helsinn Healthcare S.A.
Regulatory

Was the study required by a regulatory body?

Yes

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

EU RMP category 1 (imposed as condition of marketing authorisation)