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

Sponsor
Center for Epidemiology and Health Research, Germany (Other)
Overall Status
Completed
CT.gov ID
NCT01009684
Collaborator
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma (Industry)
50,203
1
94
534.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase

    Detailed 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'.

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    50203 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    INAS-SCORE International Active Surveillance Study - Safety of Contraceptives: Role of Estrogens
    Study Start Date :
    Aug 1, 2009
    Actual Primary Completion Date :
    Feb 1, 2017
    Actual Study Completion Date :
    Jun 1, 2017

    Arms and Interventions

    Arm Intervention/Treatment
    DNG/EV

    Users of the oral contraceptive containing Dienogest and Estradiol valerate

    Other OCs

    Users of oral contraceptives (OCs) containing other progestins and estrogens

    Outcome Measures

    Primary Outcome Measures

    1. Venous Thromboembolic Events (VTE) [up to 7 years]

    2. Acute Myocardial Infarction (AMI) [up to 7 years]

    3. Cerebrovascular Accidents (CVA) [up to 7 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Berlin Center for Epidemiology and Health Research Berlin Germany 10115

    Sponsors and Collaborators

    • Center for Epidemiology and Health Research, Germany
    • Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma

    Investigators

    • Principal Investigator: Klaas Heinemann, PhD, MD, MSc, Berlin Center for Epidemiology and Health Research

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Klaas Heinemann, MD, PhD, Principal Investigator, Center for Epidemiology and Health Research, Germany
    ClinicalTrials.gov Identifier:
    NCT01009684
    Other Study ID Numbers:
    • ZEG2009_01
    First Posted:
    Nov 9, 2009
    Last Update Posted:
    Jun 17, 2019
    Last Verified:
    Jun 1, 2019
    Keywords provided by Klaas Heinemann, MD, PhD, Principal Investigator, Center for Epidemiology and Health Research, Germany

    Study Results

    No Results Posted as of Jun 17, 2019