European Active Surveillance Study (EURAS)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Users of Drospirenone (DRSP)
|
Drug: Drospirenone
|
| Users of Levonorgestrel (LNG)
|
Drug: Levonorgestrel
|
| Users of other oral contraceptives (OCs)
|
Drug: Other progestin containing oral contraceptive
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Venous Thromboembolism (VTE) [1.5 to 5 years]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Center for Epidemiology and Health Research | Berlin | Germany | 10115 |
Sponsors and Collaborators
- Center for Epidemiology and Health Research, Germany
- Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Investigators
- Principal Investigator: Juergen C Dinger, MD, PhD, Center for Epidemiology and Health Research
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ZEG 2000_1
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Users of Drospirenone (DRSP) | Users of Levonorgestrel (LNG) | Users of Other Oral Contraceptives (OCs) |
|---|---|---|---|
| Arm/Group Description | Women who use oral contraceptives (OCs) containing DRSP as progestin | Women who use oral contraceptives (OCs) containing LNG as progestin | Women who use oral contraceptives (OCs) containing other progestins |
| Period Title: Overall Study | |||
| STARTED | 16534 | 15428 | 26341 |
| COMPLETED | 16133 | 15009 | 25762 |
| NOT COMPLETED | 401 | 419 | 579 |
Baseline Characteristics
| Arm/Group Title | Users of Drospirenone (DRSP) | Users of Levonorgestrel (LNG) | Users of Other Oral Contraceptives (OCs) | Total |
|---|---|---|---|---|
| Arm/Group Description | Women who use oral contraceptives (OCs) containing DRSP as progestin | Women who use oral contraceptives (OCs) containing LNG as progestin | Women who use oral contraceptives (OCs) containing other progestins | Total of all reporting groups |
| Overall Participants | 16534 | 15428 | 26341 | 58303 |
| Age (participants) [Number] | ||||
| <=18 years |
3,454
NaN
|
4,215
NaN
|
6,307
NaN
|
13976
24%
|
| Between 18 and 65 years |
13,080
NaN
|
11,213
NaN
|
20,034
NaN
|
44327
76%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
25.9
(8.1)
|
25.1
(8.7)
|
24.8
(7.8)
|
25.2
(8.2)
|
| Gender (participants) [Number] | ||||
| Female |
16,534
NaN
|
15,428
NaN
|
26,341
NaN
|
58303
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | ||||
| Europe |
16,534
NaN
|
15,428
NaN
|
26,341
NaN
|
58303
100%
|
Outcome Measures
| Title | Number of Participants With Venous Thromboembolism (VTE) |
|---|---|
| Description | |
| Time Frame | 1.5 to 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Users of DRSP | Users of LNG |
|---|---|---|
| Arm/Group Description | Women who use authorized oral contraceptives containing DRSP prescribed by their gynecologist | Women who use authorized oral contraceptives containing LNG prescribed by their gynecologist |
| Measure Participants | 16534 | 15428 |
| Number [Participants] |
26
0.2%
|
25
0.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Users of DRSP, Users of LNG |
|---|---|---|
| Comments | Null hypothesis: HR ≥ 2 (VTE of DRSP vs. LNG) | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Sample size calculations for VTE risk showed that 50,000 patients should be sufficient to exclude a twofold risk. | |
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.0 | |
| Confidence Interval |
() 95% 0.6 to 1.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Between 1.5 and 5 years | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Users of Drospirenone (DRSP) | Users of Levonorgestrel (LNG) | Users of Other Oral Contraceptives (OCs) | |||
| Arm/Group Description | Women who use oral contraceptives (OCs) containing DRSP as progestin | Women who use oral contraceptives (OCs) containing LNG as progestin | Women who use oral contraceptives (OCs) containing other progestins | |||
All Cause Mortality |
||||||
| Users of Drospirenone (DRSP) | Users of Levonorgestrel (LNG) | Users of Other Oral Contraceptives (OCs) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Users of Drospirenone (DRSP) | Users of Levonorgestrel (LNG) | Users of Other Oral Contraceptives (OCs) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 965/16534 (5.8%) | 1059/15428 (6.9%) | 1815/26341 (6.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Diseases of the blood and blood-forming organs | 3/16534 (0%) | 3/15428 (0%) | 12/26341 (0%) | |||
| Cardiac disorders | ||||||
| Cardiovascular diseases | 91/16534 (0.6%) | 99/15428 (0.6%) | 171/26341 (0.6%) | |||
| Endocrine disorders | ||||||
| Endocrine diseases | 34/16534 (0.2%) | 47/15428 (0.3%) | 55/26341 (0.2%) | |||
| Eye disorders | ||||||
| Eye diseases | 10/16534 (0.1%) | 17/15428 (0.1%) | 27/26341 (0.1%) | |||
| Gastrointestinal disorders | ||||||
| Digestive diseases | 121/16534 (0.7%) | 124/15428 (0.8%) | 195/26341 (0.7%) | |||
| General disorders | ||||||
| Other | 27/16534 (0.2%) | 38/15428 (0.2%) | 50/26341 (0.2%) | |||
| Infections and infestations | ||||||
| Infectious diseases | 51/16534 (0.3%) | 48/15428 (0.3%) | 82/26341 (0.3%) | |||
| Injury, poisoning and procedural complications | ||||||
| Injuries | 192/16534 (1.2%) | 207/15428 (1.3%) | 372/26341 (1.4%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Diseases of the musculoskeletal system | 151/16534 (0.9%) | 162/15428 (1.1%) | 261/26341 (1%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Malignant neoplasms | 10/16534 (0.1%) | 12/15428 (0.1%) | 25/26341 (0.1%) | |||
| Benign neoplasms | 61/16534 (0.4%) | 64/15428 (0.4%) | 117/26341 (0.4%) | |||
| Psychiatric disorders | ||||||
| Psychiatric and neurological diseases | 43/16534 (0.3%) | 58/15428 (0.4%) | 109/26341 (0.4%) | |||
| Renal and urinary disorders | ||||||
| Genitourinary diseases | 91/16534 (0.6%) | 94/15428 (0.6%) | 178/26341 (0.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Respiratory diseases | 21/16534 (0.1%) | 27/15428 (0.2%) | 41/26341 (0.2%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Skin diseases | 59/16534 (0.4%) | 59/15428 (0.4%) | 120/26341 (0.5%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Users of Drospirenone (DRSP) | Users of Levonorgestrel (LNG) | Users of Other Oral Contraceptives (OCs) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/16534 (0%) | 0/15428 (0%) | 0/26341 (0%) | |||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Juergen Dinger, MD, PhD, Principal Investigator |
|---|---|
| Organization | Berlin Center for Epidemiology and Health Research, Germany |
| Phone | +49 30 94510145 |
| dinger@zeg-berlin.de |
- ZEG 2000_1