Status: Ongoing First registered on: 31/03/2017
Last updated on: 05/05/2021
1. Study identification
EU PAS Register NumberEUPAS18358
Official titleNon-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®)
Study title acronym
Study typeObservational study
Brief description of the studySacubitril/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).
Was this study requested by a regulator?Yes: EMA
Is the study required by a Risk Management Plan (RMP)? EU RMP category 3 (required)
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicableCLCZ696B2015
2. Research centres and Investigator details
Coordinating study entity
Centre nameNovartis Pharma AG
Centre locationBasel, Switzerland
Details of (Primary) lead investigator
Title Ms
Last name Clinical Disclosure Office
First name Novartis
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Multiple centres

In total how many centres are involved in this Study?6

Basel Pharmacoepidemiology Unit, Switzerland
Countries in which this study is being conducted
International study

Denmark
Italy
Netherlands
Spain
United Kingdom
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed01/04/201702/06/2017
Start date of data collection30/06/201701/09/2017
Start date of data analysis
Date of interim report, if expected31/12/201715/03/2018
Date of final study report30/12/2022
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesNovartis Pharma AG100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Ms
Last name Clinical Disclosure Office
First name Novartis
Address line 1Novartis Pharma AG
Address line 2CH-4002 
Address line 3 
CityBasel 
Postcode 
CountrySwitzerland
Phone number (incl. country code)41613241111 
Alternative phone number 
Fax number (incl. country code)41613248001 
Public Enquiries
Title Ms 
Last name Clinical Disclosure Office 
First name Novartis 
Address line 1Novartis Pharma AG 
Address line 2CH-4002 
Address line 3 
CityBasel 
Postcode 
CountrySwitzerland 
Phone number (incl. country code)41613241111 
Alternative phone number 
Fax number (incl. country code)41613248001 
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