International Active Surveillance Study: Safety of Estrogen Estetrol (E4) Contraceptive Study (INAS-SEECS)

NCT06186271 | Recruiting

• 1 other identifier: ZEG2022_03
• Study Type: observational
• Target: 68,100
• Locations: 1 country
• Sites: 1

Brief Summary

The combined oral contraceptive (COC) containing estetrol (E4) and drospirenone (DRSP) (E4/DRSP) is a novel oral contraceptive containing a fixed dose of E4 (14.2 mg) and DRSP (3 mg). The proposed study will address post-market requirements for E4/DRSP under section 505(o) in response to the Food and Drug Administration (FDA) request. The primary objective of the study is to characterize and compare the risks of E4/DRSP with EE/DRSP and E4/DRSP with a pooled cohort of users of EE/LNG, EE/NETA, and EE/NGM combinations (non-DRSP-containing COCs) in a study population of actual users of these preparations under routine clinical practice. The main clinical outcome of interest is VTE.

Conditions

Contraception

Keywords

Birth control

Outcome Measures

Primary Outcomes (1)

• Co-primary endpoint considering the time-to-VTE event, specifically: New VTE

  ICD-10 codes: I80.1, I80.2, I80.3, I80.8\*, I80.9, I81, I82.0, I82.2, I82.3, I82.8, I82.9, I26.\*, I63.6, I67.6, H34.8, K55.0, N28.0 The variable to determine the primary endpoint is: The average treatment effect is quantified as the hazard ratio (HR) of E4/DRSP to EE/DRSP and E4/DRSP to non-DRSP COCs. VTE events are measured as the occurrence (or absence) of a new (non-recurrent) confirmed VTE during follow-up.

  Up to 24 months post baseline

Secondary Outcomes (6)

• Incidence rate and time-to-event of ATE, including acute myocardial infarction

  Up to 24 months post baseline

• Incidence rate and time-to-event of deep venous thrombosis (DVT) of the lower extremities

  Up to 24 months post baseline

• Incidence rate and time-to-event of pulmonary embolism (PE)

  Up to 24 months post baseline

• Incidence rate and time-to-event of VTE and ATE, stratified analyses

  Up to 24 months post baseline

• Incidence rate and time-to-event of discontinuation/switching

  Up to 24 months post baseline

Study Arms (3)

E4/DRSP

E4/DRSP: estetrol/drospirenone new users (starters and restarters with at least two months break)

EE/DRSP

EE/DRSP: ethinyl estradiol/drospirenone new users (starters and restarters with at least two months break)

EE/LNG and EE/NETA and EE/NGM

EE/LNG: ethinyl estradiol/levonorgestrel EE/NETA: ethinyl estradiol/norethisterone/norethindrone acetate EE/NGM: ethinyl estradiol/norgestimate new users (starters and restarters with at least two months break)

Eligibility Criteria

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

Study Population

Approximately 68,100 study participants (22,700 E4/DRSP, 22,700 EE/DRSP, and 22,700 EE/LNG, EE/NETA, and EE/NGM users) will be recruited via a network of COC-prescribing HCPs in the USA.

You may qualify if:

• New users of E4/DRSP or EE/DRSP or EE/LNG or EE/NGM or EE/NETA

You may not qualify if:

• Women who have given birth six weeks before treatment starts will be excluded from the study.

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: December 15, 2023
• First Posted: December 29, 2023
• Study Start: April 24, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: August 20, 2025

Record last verified: 2025-03

Locations

DE (1)