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Trial record 60 of 101 for:    DROSPIRENONE AND ETHINYL ESTRADIOL AND ethinylestradiol

INAS-FOCUS (International Active Surveillance Study - Folate in Oral Contraceptives Utilization Study)

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ClinicalTrials.gov Identifier: NCT01266408
Recruitment Status : Completed
First Posted : December 24, 2010
Last Update Posted : October 9, 2019
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Juergen Dinger, MD, PhD, Center for Epidemiology and Health Research, Germany

Brief 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).

Condition or disease
Contraception

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.


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Study Type : Observational
Actual Enrollment : 82921 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: International Active Surveillance Study - Folate in Oral Contraceptives Utilization Study
Actual Study Start Date : November 22, 2010
Actual Primary Completion Date : September 26, 2019

Resource links provided by the National Library of Medicine


Group/Cohort
DRSP/EE/metafolin
Women using oral contraceptives containing drospirenone, ethinylestradiol and metafolin
Other OC users
Women using oral contraceptives containing other estrogen/progestogen combinations



Primary Outcome Measures :
  1. Absolute risk of Venous Thromboembolic Events [ Time Frame: Within 6 years ]
  2. Absolute risk of Acute Myocardial Infarction [ Time Frame: Within 6 years ]
  3. Absolute risk of Cerebrovascular Accidents [ Time Frame: Within 6 years ]

Secondary Outcome Measures :
  1. Colorectal cancer [ Time Frame: Within 6 years ]
  2. Other cancer entities [ Time Frame: Within 6 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Women using oral contraceptives
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Long-term users
  • Women who do not agree to participate
  • Women with a language barrier

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01266408


Locations
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Germany
Center for Epidemiology and Health Research
Berlin, Germany, 10115
Sponsors and Collaborators
Center for Epidemiology and Health Research, Germany
Bayer
Investigators
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Principal Investigator: Juergen C Dinger, PhD, MD Center for Epidemiology and Health Research

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Responsible Party: Juergen Dinger, MD, PhD, Principal Investigator, Center for Epidemiology and Health Research, Germany
ClinicalTrials.gov Identifier: NCT01266408     History of Changes
Other Study ID Numbers: ZEG2010_02
15346 ( Other Identifier: Bayer AG )
EUPAS1597 ( Registry Identifier: EUPAS Register )
First Posted: December 24, 2010    Key Record Dates
Last Update Posted: October 9, 2019
Last Verified: October 2019
Keywords provided by Juergen Dinger, MD, PhD, Center for Epidemiology and Health Research, Germany:
Drospirenone
Dienogest
Metafolin
Folic acid
Safety
Additional relevant MeSH terms:
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Drospirenone
Contraceptive Agents
Contraceptives, Oral
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptive Agents, Female
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents