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

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

Prospective comparison of the incidence of heavy menstrual bleeding (HMB) in women of reproductive age treated with direct oral anticoagulants (DOACs)

Study Overview

• Status: Active, not recruiting
• Conditions: Heavy Menstrual Bleeding
• Intervention / Treatment: Drug: Apixaban 5 MG; Drug: Rivaroxaban 20 MG; Drug: Edoxaban 60 MG; Drug: Dabigatran 150 Mg Oral Capsule

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).

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

Study Locations

• Germany
  • Frankfurt am Main, Germany, 60389
    • Cardioangiology Center Bethanien (CCB)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Expected number of patients estimated by study duration n=150 patients treated with direct oral anticoagulants (DOAC) due to venous thromboembolism.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

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

Collaborators and Investigators

• Sponsor: Cardioangiologisches Centrum Bethanien
• Investigators: Principal Investigator: Edelgard Lindhoff-Last, Prof., Cardioangiologisches Zentrum Bethanien

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2020
• Primary Completion (Estimated): May 31, 2024
• Study Completion (Estimated): June 15, 2024

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Menstruation Disturbances; Uterine Hemorrhage; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Hemorrhage; Menorrhagia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Dabigatran; Apixaban; Edoxaban
• Other Study ID Numbers: HEMBLED

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No