ContraceptionINAS-SCORENCT01009684
International Active Surveillance Study - Safety of Contraceptives: Role of Estrogens
An observational study of Contraception, run by Center for Epidemiology and Health Research, Germany at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception
- Type of treatment
- Pill or oral medicine
- How many people
- 50,203 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2009to Jun 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Study participants are recruited by their attending gynecologists. The sample should be representative of users of oral contraceptives (OCs).
Who may be able to join
- women who have a new prescription for an OC
- women who are willing to participate in this long-term follow-up study
Who cannot join
- women who are not cooperative
- women with a language barrier
- There are no specific medical inclusion or exclusion criteria.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Berlin Center for Epidemiology and Health Research
Berlin, 10115
About this study
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.
Read the 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'.
- Conditions
- Contraception
- Keywords
- Contraception, Estradiol valerate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
Venous Thromboembolic Events (VTE)
Measured: up to 7 years
Acute Myocardial Infarction (AMI)
Measured: up to 7 years
Cerebrovascular Accidents (CVA)
Measured: up to 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2009 (estimated)
- Study startAug 2009
- Primary completionFeb 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50,203 participants (actual)
Sponsor and investigators
- Lead sponsor
- Center for Epidemiology and Health Research, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
- Responsible party
- Principal investigator, Klaas Heinemann, MD, PhD, Center for Epidemiology and Health Research, Germany
- Investigators
- Klaas Heinemann, PhD, MD, MSc, Principal investigator, Berlin Center for Epidemiology and Health Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01009684
- Sponsor's protocol ID
- ZEG2009_01
- Acronym
- INAS-SCORE
- Status last verified
- Jun 2019
- First submitted
- 6 Nov 2009
- Last updated
- 17 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dinger J, Do Minh T, Heinemann K. Impact of estrogen type on cardiovascular safety of combined oral contraceptives. Contraception. 2016 Oct;94(4):328-39. doi: 10.1016/j.contraception.2016.06.010. Epub 2016 Jun 22.
PubMed 27343748Barnett C, Hagemann C, Dinger J, Do Minh T, Heinemann K. Fertility and combined oral contraceptives - unintended pregnancies and planned pregnancies following oral contraceptive use - results from the INAS-SCORE study. Eur J Contracept Reprod Health Care. 2017 Feb;22(1):17-23. doi: 10.1080/13625187.2016.1241991. Epub 2016 Oct 17.
PubMed 27749101
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INAS-SCORE International Active Surveillance Study - Safety of Contraceptives: Role of Estrogens
- ClinicalTrials.gov ID
- NCT01009684
- Acronym / sponsor ID
- INAS-SCORE / ZEG2009_01
- Conditions
- Contraception
- Keywords
- Contraception, Estradiol valerate
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50,203 participants (actual)
- Lead sponsor
- Center for Epidemiology and Health Research, GermanyUniversity, hospital or other
- Collaborators
- Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
- Study start
- Aug 2009
- Primary completion
- Feb 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 9 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DNG/EV | – | –Users of the oral contraceptive containing Dienogest and Estradiol valerate |
| Other OCs | – | –Users of oral contraceptives (OCs) containing other progestins and estrogens |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Study participants are recruited by their attending gynecologists. The sample should be representative of users of oral contraceptives (OCs).
Key inclusion criteria (2 listed)
- women who have a new prescription for an OC
- women who are willing to participate in this long-term follow-up study
Key exclusion criteria (3 listed)
- women who are not cooperative
- women with a language barrier
- There are no specific medical inclusion or exclusion criteria.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2019.
- Results publication: PubMed 27343748Dinger J, Do Minh T, Heinemann K. Impact of estrogen type on cardiovascular safety of combined oral contraceptives. Contraception. 2016 Oct;94(4):328-39. doi: 10.1016/j.contraception.2016.06.010. Epub 2016 Jun 22.
- Results publication: PubMed 27749101Barnett C, Hagemann C, Dinger J, Do Minh T, Heinemann K. Fertility and combined oral contraceptives - unintended pregnancies and planned pregnancies following oral contraceptive use - results from the INAS-SCORE study. Eur J Contracept Reprod Health Care. 2017 Feb;22(1):17-23. doi: 10.1080/13625187.2016.1241991. Epub 2016 Oct 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Klaas Heinemann, PhD, MD, MSc principal investigator
Berlin Center for Epidemiology and Health Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Contraception, run by Center for Epidemiology and Health Research, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Venous Thromboembolic Events (VTE) (time frame: up to 7 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01009684, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2019.