Safety of estetrol (E4) combined with drospirenone (DRSP) birth control

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

Observational Center for Epidemiology and Health Research, Germany · NCT06186271

This study will test whether a birth control pill combining estetrol (E4) and drospirenone (DRSP) has similar risks of blood clots compared with other commonly used combined oral contraceptives in women of reproductive age.

Quick facts

Study typeObservational
Enrollment68100 (estimated)
SexFemale
SponsorCenter for Epidemiology and Health Research, Germany Academic / other
Locations1 site (Berlin, State of Berlin)
Trial IDNCT06186271 on ClinicalTrials.gov

What this trial studies

This is an international observational post‑marketing safety study comparing new users of the estetrol/drospirenone (E4/DRSP) oral contraceptive with new users of EE/DRSP and with a pooled cohort of EE/LNG, EE/NETA, and EE/NGM users. The main clinical outcomes are venous thromboembolism (VTE) and arterial thromboembolism (ATE), measured in routine clinical practice across participating sites. The study enrolls new users, includes an adequate number of obese women for subgroup analyses, and is sized to rule out a two‑fold increase in VTE risk for the primary comparisons. It is being conducted to meet FDA post‑market requirements and is coordinated by the Center for Epidemiology and Health Research in Germany.

Who should consider this trial

Good fit: Women of reproductive age who are new users of combined oral contraceptives—specifically those starting E4/DRSP, EE/DRSP, or EE combined with levonorgestrel, norethisterone/NETA, or norgestimate—are the intended participants.

Not a fit: Women who are not starting one of these combined oral pills, those who gave birth within the past six weeks, or users of non‑combined or non‑oral contraceptives are unlikely to benefit from joining.

Why it matters

Potential benefit: If successful, the results could reassure patients and clinicians that E4/DRSP does not carry a higher risk of blood clots than other combined oral contraceptives, expanding safe contraceptive choices.

How similar studies have performed: Early clinical trials and laboratory data indicated E4/DRSP may have less impact on hepatic parameters and hemostasis than EE combinations, and E4/DRSP has regulatory approval in several regions, but large real‑world comparative safety data on clotting risks remain limited.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

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

Exclusion Criteria:

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

Where this trial is running

Berlin, State of Berlin

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions ContraceptionBirth control
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.