Study identification

PURI

https://redirect.ema.europa.eu/resource/49019

EU PAS number

EUPAS18214

Study ID

49019

Official title and acronym

Non-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

DARWIN EU® study

No

Study countries

Denmark
Germany
Italy
Netherlands
Spain
United Kingdom

Study description

Sacubitril/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.

Study status

Finalised
Research institutions and networks

Institutions

Contact details

Novartis Clinical Disclosure Officer

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
Study protocol
Initial protocol

LCZ696B2014-Redacted-Protocol

English (1.23 MB - PDF)View document
Updated protocol

LCZ696B2014-v01.1--protocol_15Sep2022_Redacted

English (1.58 MB - PDF)View document
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)