European Active Surveillance Study of Women Taking Hormone Replacement Therapy (HRT)

Study Overview
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Brief Summary
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The objective of the active surveillance study is to compare incidence rates of serious adverse events in users of all types of newly prescribed oral continuous combined HRT products. The primary focus is the assessment of pertinent cardiovascular outcomes (such as venous and arterial thromboembolism) in new HRT users for up to 8.5 years.

Detailed Description
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The safety of a novel drug product containing a new chemical entity should be assessed in an extensive post marketing safety surveillance program. It is also prudent to assess both, the safety outcomes that relate specifically to the targeted population, as well as those that could potentially be related to the special pharmacological characteristics of the novel drug product. Differentiating between the inherent background population risk and a potential incremental risk due to treatment is often challenging. Active safety surveillance using valid epidemiological study designs has been proven to be a pertinent and reliable method to approach this endeavour. The primary objective of the study, the European Active Surveillance Study of Women taking HRT (EURAS-HRT), is to compare incidence rates of serious adverse events in users of all types of newly prescribed oral continuous combined HRT products. This active surveillance study will assess pertinent cardiovascular outcomes in new HRT users over a study period of up to 8.5 years. Also, all other serious adverse events will be reported. The new drug product under surveillance in the EURAS - HRT study contains the novel synthetic progestagen drospirenone (DRSP) combined with estradiol. As estrogen/progestagen combinations increase the risk for thromboembolism, all new drug products that contain a novel estrogen or progestagen should be investigated for their influence on venous and arterial thromboembolic events rates. A large, prospective, controlled cohort study of OC users (EURAS OC study), which compared DRSP-containing OC users with other OC users, demonstrated that DRSP is not associated with an increased incidence for any of the above-mentioned adverse events in OC users. However, because OC users are two to three decades younger than the typical HRT user the results of the OC study can only partially be extrapolated to older age groups. The participating women will complete a baseline survey using a self-administered questionnaire to describe the baseline risk. After 6 months, 12 months, and then on an annual basis, they will fill out a questionnaire in which they record complaints and events during the use of the prescribed HRTs. All adverse outcomes (including cancer) occurring during the observational period will be evaluated additionally. Reported serious adverse events will be validated and analyzed. As study participants may switch from oral continuous combined products to other oral or non-oral HRT products the outcomes for these preparation are recorded too. However, these results represent not the scientific focus of the study. Based on experience obtained in previous HRT studies, complex sources of bias and confounding are expected. Multivariate methods will therefore be used to adjust for confounding.

Official Title
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European Active Surveillance Study of Women Taking HRT

Conditions
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Menopausal Symptoms

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All women aged 40 or more years who started use of a new oral HRT at the time of inclusion in the study Exclusion Criteria: Women who do not consent to participate in the study

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>New users of oral continuous combined HRT containing drospirenone | |
| 2<br>New users of oral continuous combined HRT containing other progestagens | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Venous Thromboembolism (e.g., Deep Venous Thrombosis and Pulmonary Embolism) | Venous thromboembolism (VTE) linked to the use of continuous combined HRT containing both drospirenone (DRSP) and estradiol (E2) or to other oral continuous combined HRT preparations. | within 8.5 years | 
| Arterial Thromboembolism (e.g., Acute Myocardial Infarction and Stroke) | Arterial thromboembolism (ATE) linked to the use of continuous combined HRT containing both drospirenone (DRSP) and estradiol (E2) or to other oral continuous combined HRT preparations. | within 8.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HRT, Postmenopause