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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01009684
Recruitment Status : Completed
First Posted : November 9, 2009
Last Update Posted : June 17, 2019
Sponsor:
Collaborator:
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Information provided by (Responsible Party):
Klaas Heinemann, MD, PhD, Center for Epidemiology and Health Research, Germany

Tracking Information
First Submitted Date November 6, 2009
First Posted Date November 9, 2009
Last Update Posted Date June 17, 2019
Study Start Date August 2009
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 25, 2015)
  • 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 ]
Original Primary Outcome Measures
 (submitted: November 6, 2009)
  • Venous Thromboembolic Events (VTE) [ Time Frame: September 2009 - September 2014 ]
  • Acute Myocardial Infarction (AMI) [ Time Frame: September 2009 - September 2014 ]
  • Cerebrovascular Accidents (CVA) [ Time Frame: September 2009 - September 2014 ]
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title International Active Surveillance Study - Safety of Contraceptives: Role of Estrogens
Official Title INAS-SCORE International Active Surveillance Study - Safety of Contraceptives: Role of Estrogens
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.
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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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).
Condition Contraception
Intervention Not Provided
Study Groups/Cohorts
  • DNG/EV
    Users of the oral contraceptive containing Dienogest and Estradiol valerate
  • Other OCs
    Users of oral contraceptives (OCs) containing other progestins and estrogens
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: March 25, 2015)
50203
Original Estimated Enrollment
 (submitted: November 6, 2009)
500000
Actual Study Completion Date June 2017
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria

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.

Sex/Gender
Sexes Eligible for Study: Female
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Germany
Removed Location Countries  
 
Administrative Information
NCT Number NCT01009684
Other Study ID Numbers ZEG2009_01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Klaas Heinemann, MD, PhD, Center for Epidemiology and Health Research, Germany
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
PRS Account Center for Epidemiology and Health Research, Germany
Verification Date June 2019