Status: Ongoing First registered on: 24/03/2017
Last updated on: 05/05/2021
1. Study identification
EU PAS Register NumberEUPAS18214
Official titleNon-interventional post-authorization multi-database safety study to characterize the risk of angioedema and other specific safety events of interest in association with use of Entresto® (sacubitril/valsartan) in adult patients with heart failure
Study title acronym
Study typeObservational study
Brief description of the studySacubitril/valsartan exhibits a novel mechanism of action to treat heart failure (HF) by simultaneously inhibiting neprilysin (neutral endopeptidase; NEP) via LBQ657, the active metabolite of the prodrug sacubitril, and by blocking the angiotensin II type-1 (AT1) receptor via valsartan. It was approved in the European Union (EU) in November 2015 for treatment of symptomatic chronic heart failure with reduced ejection fraction. As agreed with the Committee for Medicinal Products for Human Use (CHMP), the Marketing Authorisation Holder of Sacubitril/valsartan will conduct a non-imposed non-interventional Post-Authorization Safety Study (PASS; category 3) to estimate the incidence and relative risks of angioedema, as well as the incidence of hypotension, hyperkalaemia, hepatotoxicity, and renal impairment in adult patients diagnosed with HF (prevalent and incident) newly starting sacubitril/valsartan or using angiotensin-converting enzyme inhibitors (ACEIs). Therefore, a multi-database cohort study with secondary use of five European healthcare databases will be performed. The following databases will be used: CPRD (The 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 applicableCLCZ696B2014
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 Officer
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
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed01/04/201708/06/2017
Start date of data collection30/06/201701/09/2017
Start date of data analysis
Date of interim report, if expected31/03/201815/03/2018
Date of final study report31/12/2022
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 Officer
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 Officer 
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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