RIVET - Retrospective Cohort Study on the Risk of Venous Thromboembolism

NCT02828904 | Completed DMC

• 1 other identifier: ZEG2014_05
• Study Type: observational
• Target: 124,000
• Locations: 1 country
• Sites: 1

Brief Summary

The risk of venous thromboembolism (VTE) associated with the use of chlormadinone acetate (CMA) compared to the gold-standard progestin levonorgestrel (LNG) as component of combined oral contraceptives (COC) is currently unknown. The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) recommended a pooled analysis of four prospective cohort studies carried out by the Berlin Center for Epidemiology and Health Research (ZEG Berlin) in order to clarify whether CMA-containing COCs carry a different VTE risk compared to LNG-containing COCs.

Conditions

Venous Thromboembolism

Outcome Measures

Primary Outcomes (1)

• The risk of venous thromboembolic events (VTE) in the cohort of users of combined oral contraceptives (COCs) containing 2 mg CMA/30 µg EE compared to 0.15 mg LNG/30 µg EE.

  VTE risk of users of CMA 2mg / EE 30µg compared to the VTE risk of users of LNG 0.15 mg / EE 30µg.

  VTEs will be identified during the follow-up intervals, typically scheduled every 6 - 12 months, with a maximum follow-up of 10 years.

Secondary Outcomes (3)

• To assess the risk of venous thromboembolic events stratified by: COC user type, age and BMI

  During the follow-up intervals, typically scheduled every 6 - 12 months, with a maximum follow-up of 10 years.

• To assess the risk of VTE in the sub-cohort of users of COCs containing CMA compared to LNG both combined with ≤30 µg EE.

  During the follow-up intervals, typically scheduled every 6 - 12 months, with a maximum follow-up of 10 years.

• To characterize the baseline risk of users of the two formulations (lifetime history of co-morbidity, prognostic factors for VTE, co-medication, socio-demographic and life¬style data).

  During the follow-up intervals, typically scheduled every 6 - 12 months, with a maximum follow-up of 10 years.

Study Arms (2)

Users of Chlormadinone Acetate (CMA) combined with Ethinylestradiol (EE)

CMA/EE users are defined as * aged 15 to 49 years * Participation in one of the 4 observational studies conducted between 2000 and 2019 (LASS/EURAS-OC, INAS-OC, INAS-SCORE, INAS-FOCUS) * COC new user (starters, switchers, and re-starters)

Users of Levonorgestrel (LNG) combined with Ethinylestradiol (EE)

LNG/EE users are defined as * aged 15 to 49 years * Participation in one of the 4 observational studies conducted between 2000 and 2019 (LASS/EURAS-OC, INAS-OC, INAS-SCORE, INAS-FOCUS) * COC new user (starters, switchers, and re-starters)

Eligibility Criteria

• Age: 15 Years - 49 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Participants will be identified retrospectively from a pooled dataset which comprises four large, controlled, prospective, non-interventional active surveillance studies that focused on the risk of VTE associated with the use of combined oral contraceptives. All data were prospectively collected by ZEG Berlin and follow the EURAS/INAS study design. Inclusion and exclusion criteria, the method of patient recruitment and follow-up as well as research methods were similar across studies.

Sponsors & Collaborators

• Center for Epidemiology and Health Research, Germany: lead

Study Sites (1)

Center for Epidemiology and Health Research Berlin

Berlin, 10115, Germany

Location

MeSH Terms

Conditions

Venous Thromboembolism

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, MD, MSc, MBA

Study Record Dates

• First Submitted: June 20, 2016
• First Posted: July 12, 2016
• Study Start: March 10, 2022
• Primary Completion: January 15, 2024
• Study Completion: January 31, 2024
• Last Updated: March 5, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)