This trial is active, not recruiting.

Condition contraception
Sponsor Center for Epidemiology and Health Research, Germany
Collaborator Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Start date August 2009
End date December 2016
Trial size 50203 participants
Trial identifier NCT01009684, ZEG2009_01


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model cohort
Time perspective prospective
Users of the oral contraceptive containing Dienogest and Estradiol valerate
Users of oral contraceptives (OCs) containing other progestins and estrogens

Primary Outcomes

Venous Thromboembolic Events (VTE)
time frame: up to 7 years
Acute Myocardial Infarction (AMI)
time frame: up to 7 years
Cerebrovascular Accidents (CVA)
time frame: up to 7 years

Eligibility Criteria

Female participants of any age.

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.

Additional Information

Official title INAS-SCORE International Active Surveillance Study - Safety of Contraceptives: Role of Estrogens
Principal investigator Klaas Heinemann, PhD, MD, MSc
Description 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 was 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. Study amendment: Follow-up was initially expected to last until 2014 for the United States and Europe. However, the European regulatory authorities were concerned about the low proportion of Qlaira users in the United States and requested that the primary analysis should be based on the European study arm only. However, this reduction in sample size results in a reduction of the statistical power. Therefore it was agreed upon with the European regulatory authorities to extend the follow-up period in Europe till 2016. This will ensure that the statistical power in the European study arm will be as high as the originally planned power for the complete study population (European and US study population combined). The total exposure in Europe will be sufficient to exclude a twofold risk of VTE and a threefold risk of ATE for Qlaira compared to 'Other COCs'.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Center for Epidemiology and Health Research, Germany.