International Active Surveillance Study: Native Estrogen Estetrol (E4) Safety Study (INAS-NEES)

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Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/49985
• EU PAS number:
  EUPAS49984
• Study ID:
  49985
• Official title and acronym:
  International Active Surveillance Study: Native Estrogen Estetrol (E4) Safety Study (INAS-NEES)
• DARWIN EU® study:
  No
• Study countries:
  Brazil

  Czechia

  France

  Germany

  Hungary

  Italy

  Poland

  Spain

  United Kingdom

  United States
• Study description:
  The primary objective of the study is to characterize and compare the risks of E4/DRSP with EE/LNG, in a study population that is representative of the actual users of these preparations.This includes an estimate of the absolute risk of rare serious adverse outcomes. The main clinical outcome of interest is venous thromboembolism (VTE), i.e., deep venous thrombosis (DVT) of the lower extremities and pulmonary embolism (PE). Secondary objectives include measuring the occurrence of unintended pregnancy, assessing the risk of arterial thromboembolism (ATE), describing the drug utilization pattern, describing the baseline risk profile for VTE and ATE, and investigating outcomes associated with foetal exposure to E4/DRSP. It is a multinational, comparative, prospective, active surveillance study that follows two cohorts. The cohorts consist of new users (starters and restarters) of two different groups of hormonal contraceptives: E4/DRSP and EE/LNG. The study is taking a non-interventional approach to provide comprehensive information on these treatments in a routine clinical practice setting. Study participants will be enrolled via an international network of COC-prescribing health care professionals (HCPs) and then followed up for one to two years. All outcomes of interest will be captured by direct contact with the study participants. Reported outcomes of interest will be validated via attending physicians and relevant source documents. The classification of outcomes of interest into ‘confirmed’ and ‘not confirmed’ will be verified by blinded independent adjudication. Approximately 101,000 study participants (50,500 E4/DRSP and 50,500 EE/LNG new users) will be recruited via a network of COC-prescribing health care professionals in Europe, the USA, and Brazil. All new users (starters and restarters) prescribed E4/DRSP or EE/LNG who are willing to participate may be eligible for enrolment in the study.
• Study status:
  Planned

Research institutions and networks

Institutions

Berlin Center for Epidemiology & Health Research, ZEG Berlin

Germany

Study timelines

Date when funding contract was signed

Actual: 01/07/2022

Study start date

Planned: 31/03/2023

Date of interim report, if expected

Planned: 23/06/2023

Date of final study report

Planned: 22/06/2029

Sources of funding

Pharmaceutical company and other private sector 

More details on funding

Estetra SRL

Study protocol

Initial protocol

INAS-NEES_EMAProtocol_V04-00_20220908

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)