Contraception
Conditions
Keywords
Venous thromboembolism, Drospirenone
Brief summary
EURAS is a multi-national, controlled, prospective, post-marketing, non-intervention cohort study of new users of drospirenone/ethinylestradiol (DRSP/EE), levonorgestrel/ethinylestradiol (LNG/EE) and other oral contraceptives (OCs) under routine conditions of medical practice in seven European countries. Baseline survey and semiannual, active follow-up are based on postal questionnaires, with validation of reported events by the women's treating physicians. A multifaceted 4-level follow-up procedure will be established to ensure low loss to follow-up rates. The objective of the study is the investigation of the incidence of rare serious adverse events associated with the use of new and established OCs, and specifically the incidence of thromboembolic events.
Detailed description
Active surveillance using valid epidemiologic study designs is desirable for any new product, because adverse effects may occur that have not yet been identified in pre-marketing studies. The EURAS study investigates the safety of oral contraceptives with a large cohort of women attending offices of prescribing physicians. Its primary objective will be to compare incidence rates of adverse events in users of so-called new OCs and users of other OCs. The study is conducted as a phase IV commitment to the European Drug Authorities. The combined cohort will include 50,000 to 60,000 women recruited by a selected set of physicians in six European countries. A total of more than 1,500,000 cycles are expected to be observed during the field work which will start early in 2001 and end early in 2006. The participating women will undergo a baseline survey using a self administered questionnaire to describe the baseline risk. Every six months they will fill out a questionnaire in which they will record complaints and events during the use of the prescribed OC which will be validated. A multifaceted 4-level follow-up procedure will be established to ensure low loss to follow-up rates. Based on experience obtained in previous OC studies complex sources of bias and confounding are expected. Thus, multivariate methods such as Cox regression will be used to adjust for confounding. Regarding the impact of the results on public health, the main emphasis will be on the absolute risk estimates.
Interventions
Sponsors
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Center for Epidemiology and Health Research, Germany
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
Yes
Inclusion criteria
* Women starting OC use or women switching OCs * Women willing to participate in the active surveillance for several years
Exclusion criteria
* Women who have contraindications for OC use
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Venous Thromboembolism (VTE) | 1.5 to 5 years |
Countries
Germany
Participant flow
Pre-assignment details
A total of 59510 women were enrolled. Thereof 836 were excluded as they did not sign the informed consent form, were enrolled two or more times, continued their old OC or did not start OC use. In addition 371 used non oral hormonal contraception at study entry. These women were only used for the comparison of baseline risks.
Participants by arm
| Arm | Count |
|---|---|
| Users of Drospirenone (DRSP) Women who use oral contraceptives (OCs) containing DRSP as progestin | 16,534 |
| Users of Levonorgestrel (LNG) Women who use oral contraceptives (OCs) containing LNG as progestin | 15,428 |
| Users of Other Oral Contraceptives (OCs) Women who use oral contraceptives (OCs) containing other progestins | 26,341 |
| Total | 58,303 |
Baseline characteristics
| Characteristic | Users of Levonorgestrel (LNG) | Users of Other Oral Contraceptives (OCs) | Users of Drospirenone (DRSP) | Total |
|---|---|---|---|---|
| Age Categorical <=18 years | 4,215 participants | 6,307 participants | 3,454 participants | 13976 participants |
| Age Categorical >=65 years | 0 participants | 0 participants | 0 participants | 0 participants |
| Age Categorical Between 18 and 65 years | 11,213 participants | 20,034 participants | 13,080 participants | 44327 participants |
| Age Continuous | 25.1 years STANDARD_DEVIATION 8.7 | 24.8 years STANDARD_DEVIATION 7.8 | 25.9 years STANDARD_DEVIATION 8.1 | 25.2 years STANDARD_DEVIATION 8.2 |
| Gender Female | 15,428 participants | 26,341 participants | 16,534 participants | 58303 participants |
| Gender Male | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Europe | 15,428 participants | 26,341 participants | 16,534 participants | 58303 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 16,534 | 0 / 15,428 | 0 / 26,341 |
| serious Total, serious adverse events | 965 / 16,534 | 1,059 / 15,428 | 1,815 / 26,341 |
Outcome results
Primary
Number of Participants With Venous Thromboembolism (VTE)
Time frame: 1.5 to 5 years
Population: The primary analysis compares the users of DRSP and LNG. Its results are presented below. The comparison of users of DRSP and OCs containing other progestins was only conducted for exploratory reasons. This secondary analysis showed similar results and is described in more detail in the publication of study results, see citations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Users of DRSP | Number of Participants With Venous Thromboembolism (VTE) | 26 Participants |
| Users of LNG | Number of Participants With Venous Thromboembolism (VTE) | 25 Participants |
Comparison: Null hypothesis: HR ≥ 2 (VTE of DRSP vs. LNG)p-value: <0.0595% CI: [0.6, 1.8]Regression, Cox