ContraceptionNCT01266408
INAS-FOCUS (International Active Surveillance Study - Folate in Oral Contraceptives Utilization Study)
An observational study of Contraception, run by Center for Epidemiology and Health Research, Germany at 1 site in Germany.
Trial summary
The study compares the risks of short- and long-term use of contraceptives containing drospirenone (DRSP) or dienogest (DNG)/ethinylestradiol (EE) plus levomefolate calcium (metafolin) with the risks of short- and long-term use of other established oral contraceptives (OCs). 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
- 82,921 participants
- Where
- 1 siteGermany
- Study dates
- 22 Nov 2010to 2 Oct 2019
- 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: Women using oral contraceptives
Who may be able to join
- Women starting OC use ("starters")
- Women switching OC use without a pill intake break ("switchers")
- Women restarting OC use after a pill intake break ("restarters")
- Women willing to participate in the active surveillance
Who cannot join
- Long-term users
- Women who do not agree to participate
- Women with a language barrier
Trial locations and contacts
1 site in 1 country.
About this study
Official title: International Active Surveillance Study - Folate in Oral Contraceptives Utilization Study
The study compares the risks of short- and long-term use of contraceptives containing drospirenone (DRSP) or dienogest (DNG)/ethinylestradiol (EE) plus levomefolate calcium (metafolin) with the risks of short- and long-term use of other established oral contraceptives (OCs).
Read the detailed description
New oral contraceptives (OCs) containing drospirenone (DRSP) or dienogest (DNG)/ethinylestradiol (EE) plus levomefolate calcium (metafolin) have been recently introduced and will be introduced in a number of countries in the near future. Although the safety of OCs has improved over the last 50 years with reductions in the estrogen and progestogen dose, special attention regarding oral contraceptive safety amongst women with risk factors for venous and arterial thromboembolism as well as cancer is necessary. Folic acid supplementation has been implicated in both the prevention and the promotion of several cancers, including colorectal cancer (CRC). Chronic folate deficiency seems to be associated with colorectal carcinogenesis, while high folic acid levels may have a tumor-promoting effect. On balance an oral contraceptive containing folate may be advantageous for several reasons. It may increase baseline folate levels with potential for protecting against some malignancies and concurrently decrease the risk of neural tube defects in women who become pregnant due to OC-failure, incorrect OC-use or after stopping the OC for a planned pregnancy. Although unexpected, it is unclear whether combined oral contraceptives plus metafolin in general and specifically DRSP/EE plus metafolin and DNG/EE plus metafolin will alter the risk profile of established oral contraceptives.
This study investigates the safety of these new oral contraceptives with regard to cardiovascular outcomes and colorectal cancer.
INAS-FOCUS is a prospective, controlled, non-interventional cohort study with three study arms: users of DRSP/EE/metafolin, users of DNG/EE/metafolin and users of OCs containing other estrogen/progestogen combinations. The users will be grouped to starters (first-ever users), switchers (women switching OC without a pill intake break) and restarters (women with a pill intake break). Users of an OC are accrued by a network of prescribing physicians. Baseline and follow-up information is collected via a self-administered questionnaire. Data analysis will be based on life-table methods comparing the cohorts.
Amendment, approved by the Safety Monitoring and Advisory Council on 13th May 2018:
During study recruitment, only one combined oral contraceptive was launched containing metafolin (DRSP/EE+) and the planned third cohort arm (users of DNG/EE+) was rendered obsolete.
In addition, early recruitment rates and exposure figures in INAS-FOCUS suggested that the study would be inadequately powered to accurately assess the risk of colorectal cancer at 15 years. Interim reports were presented to the Safety Monitoring and Advisory Council (SMAC) and in consultation with the funder, a decision made to discontinue INAS-FOCUS following analysis of cardiovascular events (Part 1 of study). The current protocol reflects the developments discussed above. The original three cohorts have been reduced to two (DRSP/EE+ and other OCs containing estrogen/progestogen) and Part II (long-term assessment of risk of colorectal cancer) has been removed from the protocol. Colorectal cancer outcomes will be analyzed as a secondary outcome for signal detection purposes only.
For historical accuracy and context, the introduction and background sections of the protocol have been left unchanged.
- Conditions
- Contraception
- Keywords
- Drospirenone, Dienogest, Metafolin, Folic acid, Safety
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 |
|---|---|---|
| DRSP/EE/metafolin | Women using oral contraceptives containing drospirenone, ethinylestradiol and metafolin | |
| Other OC users | Women using oral contraceptives containing other estrogen/progestogen combinations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute risk of Venous Thromboembolic Events
Measured: Within 6 years
Absolute risk of Acute Myocardial Infarction
Measured: Within 6 years
Absolute risk of Cerebrovascular Accidents
Measured: Within 6 years
Secondary outcomes (2)
Colorectal cancer
Measured: Within 6 years
Other cancer entities
Measured: Within 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2010 (estimated)
- Study start22 Nov 2010
- Primary completion29 Sep 2019
- Study completion2 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 82,921 participants (actual)
Sponsor and investigators
- Lead sponsor
- Center for Epidemiology and Health Research, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Principal investigator, Juergen Dinger, MD, PhD, Center for Epidemiology and Health Research, Germany
- Investigators
- Juergen C Dinger, PhD, MD, Principal investigator, Center for Epidemiology and Health Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01266408
- Sponsor's protocol ID
- ZEG2010_02
- Other IDs
- 15346, EUPAS1597
- Status last verified
- Jul 2020
- First submitted
- 23 Dec 2010
- Last updated
- 28 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Active Surveillance Study - Folate in Oral Contraceptives Utilization Study
- ClinicalTrials.gov ID
- NCT01266408
- Acronym / sponsor ID
- ZEG2010_02
- Conditions
- Contraception
- Keywords
- Drospirenone, Dienogest, Metafolin, Folic acid, Safety
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 82,921 participants (actual)
- Lead sponsor
- Center for Epidemiology and Health Research, GermanyUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- 22 Nov 2010 (actual)
- Primary completion
- 29 Sep 2019 (actual)
- Study completion
- 2 Oct 2019 (actual)
- First posted
- 24 Dec 2010 (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 study compares the risks of short- and long-term use of contraceptives containing drospirenone (DRSP) or dienogest (DNG)/ethinylestradiol (EE) plus levomefolate calcium (metafolin) with the risks of short- and long-term use of other established oral contraceptives (OCs).
Detailed description
New oral contraceptives (OCs) containing drospirenone (DRSP) or dienogest (DNG)/ethinylestradiol (EE) plus levomefolate calcium (metafolin) have been recently introduced and will be introduced in a number of countries in the near future. Although the safety of OCs has improved over the last 50 years with reductions in the estrogen and progestogen dose, special attention regarding oral contraceptive safety amongst women with risk factors for venous and arterial thromboembolism as well as cancer is necessary. Folic acid supplementation has been implicated in both the prevention and the promotion of several cancers, including colorectal cancer (CRC). Chronic folate deficiency seems to be associated with colorectal carcinogenesis, while high folic acid levels may have a tumor-promoting effect. On balance an oral contraceptive containing folate may be advantageous for several reasons. It may increase baseline folate levels with potential for protecting against some malignancies and concurrently decrease the risk of neural tube defects in women who become pregnant due to OC-failure, incorrect OC-use or after stopping the OC for a planned pregnancy. Although unexpected, it is unclear whether combined oral contraceptives plus metafolin in general and specifically DRSP/EE plus metafolin and DNG/EE plus metafolin will alter the risk profile of established oral contraceptives.
This study investigates the safety of these new oral contraceptives with regard to cardiovascular outcomes and colorectal cancer.
INAS-FOCUS is a prospective, controlled, non-interventional cohort study with three study arms: users of DRSP/EE/metafolin, users of DNG/EE/metafolin and users of OCs containing other estrogen/progestogen combinations. The users will be grouped to starters (first-ever users), switchers (women switching OC without a pill intake break) and restarters (women with a pill intake break). Users of an OC are accrued by a network of prescribing physicians. Baseline and follow-up information is collected via a self-administered questionnaire. Data analysis will be based on life-table methods comparing the cohorts.
Amendment, approved by the Safety Monitoring and Advisory Council on 13th May 2018:
During study recruitment, only one combined oral contraceptive was launched containing metafolin (DRSP/EE+) and the planned third cohort arm (users of DNG/EE+) was rendered obsolete.
In addition, early recruitment rates and exposure figures in INAS-FOCUS suggested that the study would be inadequately powered to accurately assess the risk of colorectal cancer at 15 years. Interim reports were presented to the Safety Monitoring and Advisory Council (SMAC) and in consultation with the funder, a decision made to discontinue INAS-FOCUS following analysis of cardiovascular events (Part 1 of study). The current protocol reflects the developments discussed above. The original three cohorts have been reduced to two (DRSP/EE+ and other OCs containing estrogen/progestogen) and Part II (long-term assessment of risk of colorectal cancer) has been removed from the protocol. Colorectal cancer outcomes will be analyzed as a secondary outcome for signal detection purposes only.
For historical accuracy and context, the introduction and background sections of the protocol have been left unchanged.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DRSP/EE/metafolin | – | –Women using oral contraceptives containing drospirenone, ethinylestradiol and metafolin |
| Other OC users | – | –Women using oral contraceptives containing other estrogen/progestogen combinations |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Women using oral contraceptives
Key inclusion criteria (4 listed)
- Women starting OC use ("starters")
- Women switching OC use without a pill intake break ("switchers")
- Women restarting OC use after a pill intake break ("restarters")
- Women willing to participate in the active surveillance
Key exclusion criteria (3 listed)
- Long-term users
- Women who do not agree to participate
- Women with a language barrier
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
Absolute risk of Venous Thromboembolic Events
Time frame: Within 6 years
Absolute risk of Acute Myocardial Infarction
Time frame: Within 6 years
Absolute risk of Cerebrovascular Accidents
Time frame: Within 6 years
2 secondary outcomes
Colorectal cancer
Time frame: Within 6 years
Other cancer entities
Time frame: Within 6 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 28 Jul 2020.
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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.
Juergen C Dinger, PhD, MD principal investigator
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 4 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 28 Jul 2020. 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?
Absolute risk of Venous Thromboembolic Events (time frame: Within 6 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?
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 28 Jul 2020.