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

June 14, 2019 updated by: Klaas Heinemann, MD, PhD, Center for Epidemiology and Health Research, Germany

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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

50203

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 10115
        • Berlin Center for Epidemiology and Health Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Study participants are recruited by their attending gynecologists. The sample should be representative of users of oral contraceptives (OCs).

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Venous Thromboembolic Events (VTE)
Time Frame: up to 7 years
up to 7 years
Acute Myocardial Infarction (AMI)
Time Frame: up to 7 years
up to 7 years
Cerebrovascular Accidents (CVA)
Time Frame: up to 7 years
up to 7 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Center for Epidemiology and Health Research, Germany

Collaborators

Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2009

Primary Completion (ACTUAL)

February 1, 2017

Study Completion (ACTUAL)

June 1, 2017

Study Registration Dates

First Submitted

November 6, 2009

First Submitted That Met QC Criteria

November 6, 2009

First Posted (ESTIMATE)

November 9, 2009

Study Record Updates

Last Update Posted (ACTUAL)

June 17, 2019

Last Update Submitted That Met QC Criteria

June 14, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • ZEG2009_01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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