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

NCT06028555 | Recruiting

• 1 other identifier: ZEG2022_02
• Study Type: observational
• Target: 101,000
• Locations: 1 country
• Sites: 1

Brief Summary

Multinational, comparative, prospective, active surveillance study that follows two cohorts. The primary objective of the study is to characterize and compare the risks of E4/Drospirenone (DRSP) with levonorgestrel-containing combined oral contraceptives (EE/LNG) in a study population that is representative of the actual users of these preparations. The main clinical outcome of interest is venous thromboembolism (VTE), specifically deep venous thrombosis (DVT) 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.

Conditions

Contraception; Birth Control

Outcome Measures

Primary Outcomes (1)

• Incidence rate of Venous Thromboembolism (VTE)

  * Occurrence (or absence) of a new (non-recurrent) confirmed Deep Venous Thrombosis (DVT) of the lower extremities (International Classification of Diseases, 10th revision (ICD-10) codes: I80.1 and I80.2) and, * Occurrence (or absence) of a new (non-recurrent) confirmed Pulmonary Embolism (PE) (ICD-10 codes: I26.0 and I26.9)

  Up to 24 months post baseline

Secondary Outcomes (5)

• Incidence rate of all VTEs, including thromboses of the renal, mesenteric, portal, cerebral and retinal veins

  Up to 24 months post baseline

• Incidence rate of Arterial Thromboembolism (ATE), including acute myocardial infarction (AMI) and cerebrovascular accidents (CVA)

  Up to 24 months post baseline

• Incident rate of unintended pregnancy

  Up to 24 months post baseline

• Incident rate of neonatal malformations associated with foetal exposure to E4/DRSP and EE/LNG in E4/DRSP users and users of EE/LNG

  Up to 24 months post baseline

• Compare drug utilization pattern between users of both cohorts

  Up to 24 months post baseline

Study Arms (2)

Estetrol/drospirenone (E4/DRSP)

Users: Starters and re-starters

Ethinyl estradiol/levonorgestrel (EE/LNG)

Users: Starters and re-starters

Eligibility Criteria

• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Approximately 50,500 E4/ DRSP users and 50,500 EE/LNG new users, including adolescents (below the age of 18 years eligible based on local legislation) will be recruited via recruitment centres.

You may qualify if:

• New users of E4/DRSP New users of EE/LNG Germany: only recruitment of study participants who are prescribed the COC within on-label use

Sponsors & Collaborators

• Center for Epidemiology and Health Research, Germany: lead
• Estetra: collaborator
• Gedeon Richter Plc.: collaborator

Study Sites (1)

Berlin Center for Epidemiology and Health Research

Berlin, State of Berlin, 10115, Germany

RECRUITING

Study Officials

• Klaas Heinemann, Dr.

  ZEG Berlin GmbH

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Armin Papkalla, Dr.

CONTACT

+49 30 945 101 20; a.papkalla@zeg-berlin.de

Silke Zimmermann, Dr.

CONTACT

+49 30 945 101 20; s.zimmermann@zeg-berlin.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2023
• First Posted: September 8, 2023
• Study Start: June 28, 2023
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2028
• Last Updated: August 17, 2025

Record last verified: 2025-08

Locations

DE (1)