International Active Surveillance Study - Safety of Contraceptives: Role of Estrogens

Official Title: “INAS-SCORE International Active Surveillance Study - Safety of Contraceptives: Role of Estrogens”

The primary objective of the study is to assess the risks of short and long-term use of estradiol valerate/dienogest (EV/DNG) and of established oral contraceptives (OCs) in a study population that is representative for the actual users of the individual preparations.

This includes an estimate of the absolute risk of rare serious adverse outcomes.

During the development of oral contraceptives (OCs) over the last decades, ethinyl-estradiol (EE) has been reduced under the hypothesis that lower EE doses lead to a better safety profile and specifically to a lower venous thromboembolism (VTE) incidence. However, the reduction of the EE dose led to a less favorable bleeding control.

Though EE has been utilized within numerous OCs, efforts have been made to utilize estradiol (E2) and estradiol valerate (EV) which have lower impact on the hepatic system and subsequently on hemostatic parameters. Bayer Schering Pharma has developed a new EV based OC in a dosing regimen that combines both reliable contraception and acceptable bleeding profile.

The INAS-SCORE study was designed as an international, prospective, controlled, non-interventional cohort study. The study was started in Europe and will be extended to the US after the launch of the new regimen. New users of an OC (starters or switchers) are accrued by a network of prescribing physicians. Even in the event of high drop-out rates, a 3 to 5-year follow-up of 50,000 women should be sufficient to document about 150,000 women-years. Baseline and follow-up information are collected via a self-administered questionnaire. All self-reported clinical outcomes of interest will be validated via health care professionals. Classification of reported outcomes as "confirmed" or "unconfirmed" will be checked via blinded, independent adjudication. A multifaceted 4-level follow-up procedure proved to ensure low loss to follow-up rates.

The main clinical outcomes of interest for the short and long-term follow-up are cardiovascular events, primarily deep venous thrombosis, pulmonary embolism, acute myocardial infarction, and cerebrovascular accidents.

Data analysis will be based on life-table methods. All analyses will make allowance for confounding, using multivariate techniques such as Cox regression.

Arms, Groups and Cohorts in this Clinical Trial

• : DNG/EV
  • Users of the oral contraceptive containing Dienogest and Estradiol valerate
• : Other OCs
  • Users of oral contraceptives (OCs) containing other progestins and estrogens

Primary Measures

• Venous Thromboembolic Events (VTE)
  • Time Frame: September 2009 - September 2014
    Safety Issue?: Yes
• Acute Myocardial Infarction (AMI)
  • Time Frame: September 2009 - September 2014
    Safety Issue?: Yes
• Cerebrovascular Accidents (CVA)
  • Time Frame: September 2009 - September 2014
    Safety Issue?: Yes

Inclusion Criteria:

• women who have a new prescription for an OC
• women who are willing to participate in this long-term follow-up study

Exclusion Criteria:

• women who are not cooperative
• women with a language barrier
• There are no specific medical inclusion or exclusion criteria.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: Center for Epidemiology and Health Research, Germany Other

Overall Clinical Trial Officials and Contacts

Juergen C Dinger, MD, PhD Principal Investigator Berlin Center for Epidemiology and Health Research  

Overall Contact: Kristina Bardenheuer, MSc +49 30 945101 bardenheuer@zeg-berlin.de

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01009684

Study ID Number: ZEG2009_01

ClinicalTrials.gov Identifier: NCT01009684

Health Authority: European Union: European Medicines Agency