Prospective Comparison of Incidence of Heavy Menstrual Bleeding in Women Treated With Direct Oral Anticoagulants

Study Overview
=================
Brief Summary
-----------------
Prospective comparison of the incidence of heavy menstrual bleeding (HMB) in women of reproductive age treated with direct oral anticoagulants (DOACs)

Detailed Description
-----------------
Patients will be treated as standard of care, no randomization schedule, no blinded investigational product (IP). The decision which DOAC will be given is made before the subject will enter the trial. The DOAC has to be taken at least for seven days. The registry is non-interventional (NIS) with routine blood draw at baseline and at month 4 after inclusion. The prospective follow up will be up to four months. Three consecutive menstrual bleeding cycles will be documented by the participating patients at home. One baseline data reporting and one follow up reporting after four months are planned in the participating coagulation centers. The primary aim is the comparison of the frequency of heavy menstrual bleeding in female patients of reproductive age anticoagulated with DOACs using a modified pictorial blood loss assessment chart. Secondary aims are the prevalence of von Willebrand disease in young anticoagulated female patients and correlation of HMB with age, International Society of Thrombosis and Hemostasis bleeding assessment tool at inclusion, Blood group, anatomical reasons i.e. underlying uterine pathologies, i. e. presence of uterine fibroids, endometrial polyps and/or adenomyosis, occurrence of iron deficiency, hemoglobin level and intermittent use of non-steroidal anti-inflammatory drug (NSAID).

Official Title
-----------------
Prospective, Observational, Non-interventional Open-label Multicenter Registry Regarding the Incidence of Heavy Menstrual Bleeding in Women of Reproductive Age Treated With Direct Oral Anticoagulants Because of Venous Thromboembolism

Conditions
-----------------
Heavy Menstrual Bleeding

Intervention / Treatment
-----------------
* Drug: Apixaban 5 MG
* Drug: Rivaroxaban 20 MG
* Drug: Edoxaban 60 MG
* Drug: Dabigatran 150 Mg Oral Capsule


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women with venous thromboembolism Age: 18 - 50 years Regular menstrual bleeding Treatment with DOACs for at least 7 days before inclusion Full therapeutic anticoagulation with rivaroxaban 1 x 20 mg, apixaban 2 x 5 mg, edoxaban 60mg once daily or dabigatran 2 x 150mg for at least the next four months Written informed consent Exclusion Criteria: Hysterectomy or ovariectomy Known heavy menstrual bleeding Hormonal contraceptives Hormone replacement therapy Use of hormone releasing intrauterine System (IUS) Contraindications to treatment with DOACs Treatment with rivaroxaban 15 mg twice daily (first three weeks after diagnosis of venous thrombosis) or apixaban 10 mg twice daily (first week after diagnosis of venous thrombosis) Treatment with rivaroxaban (10 mg or 15 mg once daily) or apixaban (2,5 mg twice daily) in reduced therapeutic dosages Participation in any other trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| direct oral anticoagulant (DOAC) No.1<br>Apixaban 5mg, oral, twice daily for at least four months | Drug: Apixaban 5 MG<br>* frequency of heavy menstrual bleeding<br>* Other names: Eliquis;|
| direct oral anticoagulant (DOAC) No.2<br>Rivaroxaban 20mg, oral, once daily for at least four months | Drug: Rivaroxaban 20 MG<br>* frequency of heavy menstrual bleeding<br>* Other names: Xarelto;|
| direct oral anticoagulant (DOAC) No.3<br>Edoxaban 60mg, oral, once daily for at least four months | Drug: Edoxaban 60 MG<br>* frequency of heavy menstrual bleeding<br>* Other names: Lixiana;|
| direct oral anticoagulant (DOAC) No.4<br>Dabigatran 150mg, oral, twice daily for at least four months | Drug: Dabigatran 150 Mg Oral Capsule<br>* frequency of heavy menstrual bleeding<br>* Other names: Pradaxa;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary observation point (for all patients) | Frequency of heavy menstrual bleeding in anticoagulated female patients of reproductive Age using a modified Pictorial blood loss assessment Chart (PBAC)-Score (Higham, Br J Obstet Gynaecol 1990; 97: 734-9) | baseline and monthly up to month 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary observation points (for all patients) | Correlation of heavy menstrual bleeding with von Willebrand's disease; Age; ISTH-BAT-Score at inclusion; blood Group; anatomical reasons i.e. underlying uterine pathologies, i.e. presence of uterine fibroids, endometrial polyps and/or adenomyosis; iron deficiency; hemoglobin level; intermittent use of NSAR | up to 16 weeks |