Study identification

EU PAS number

EUPAS18358

Study ID

49003

Official title and acronym

Non-interventional post-authorization multi-database safety study to assess the risk of myotoxicity, hepatotoxicity and acute pancreatitis in statin-exposed heart failure patients with or without concomitant use of sacubitril/valsartan (Entresto®)

DARWIN EU® study

No

Study countries

Denmark
Germany
Italy
Netherlands
Spain
United Kingdom

Study description

Sacubitril/valsartan is a novel treatment initially approved in the United States, and the EU in 2015. It is indicated in adult patients for treatment of symptomatic chronic heart failure with reduced ejection fraction.
Based on the observation that sacubitril inhibits OATP1B1 and OATP1B3 transporters in vitro, a drug-drug interaction (DDI) study with atorvastatin (a HMG-CoA reductase inhibitor statin and OATP1B1 and OATP1B3 substrate) showed that sacubitril/valsartan increased the maximal plasma concentrations of atorvastatin and its metabolites by up to 2-fold.
However, the areas under the curve of atorvastatin and its metabolites were not increased to a clinically significant extent.
Based on the above, and given the high proportion of patients expected to be on a concomitant statin post-marketing, the Committee for Medicinal Products for Human Use (CHMP) requested Novartis to further evaluate this potential DDI in the post-marketing setting.
Novartis therefore committed to perform a case-control study to assess specific statin-associated safety events (namely myotoxicity, hepatotoxicity, and acute pancreatitis) in statin-exposed heart failure (HF) patients with or without concomitant use of sacubitril/valsartan using information from five European healthcare databases (i.e. CPRD Clinical Practice Research Datalink from the UK, PHARMO The PHARMO Database Network from the Netherlands, SIDIAP Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària) from Catalonia, Spain, HSD Health Search IMS Health Longitudinal Patient Database from Italy, and the Aarhus University Prescription Database and Danish National Patient Registry from Denmark).

Study status

Finalised
Research institutions and networks

Institutions

Contact details

Novartis Clinical Disclosure Office

Primary lead investigator

Study timelines

Date when funding contract was signed

Planned:
Actual:

Study start date

Planned:
Actual:

Date of interim report, if expected

Planned:
Actual:

Date of final study report

Planned:
Actual:
Sources of funding
Pharmaceutical company and other private sector 

More details on funding

Novartis Pharma AG
Regulatory

Was the study required by a regulatory body?

Yes

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

EU RMP category 3 (required)