Bleeding in Multiple Myeloma
NCT Number: NCT06482931
Acronym: BiMM
Status: NOT_YET_RECRUITING
Study Type: OBSERVATIONAL
Conditions: Multiple Myeloma
Interventions: OTHER: Quality of life questionnaires
Sponsor: University Medical Center Groningen
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 160
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-10-01
Completion Date: 2027-12-31

Summary:
* Background Multiple myeloma (MM) is a haematological malignancy characterised by uncontrolled plasma cell proliferation leading to bone damage, anaemia, kidney failure, and hypercalcemia. Venous thromboembolism (VTE) represents a significant concern in MM and more than 10% of patients develop a VTE. The currently most used thromboprophylaxis regimens consist of either aspirin or prophylactic low molecular weight heparin (LMWH). The choice between the two depends on patient risk assessment according to the International Myeloma Working Group (IMWG) guidelines. Due to the associated high VTE risk, MM patients have an inherent need for thromboprophylaxis which is an essential part of their care. The previous randomized controlled trials (RCTs) comparing aspirin with LMWH observed no major bleeding events and only one minor bleeding in the LMWH group and when comparing aspirin with LMWH and warfarin, major bleeding events were observed only in three patients (1.4%) who received aspirin. Moreover, six patients (2.7%) in the aspirin group, one patient (0.5%) in the warfarin group, and three patients (1.4%) in the LMWH group experienced minor bleeding events. However, clinically relevant non-major bleedings (CRNMBs) were not reported, and the follow-up varied widely between the two studies. The risk-benefit ratio between the different regimens is yet unclear and it is difficult to conclude which anticoagulation should be implemented as standard of care in daily practice. Moreover, the current regimens, namely LMWH, might be perceived as burdensome by MM patients due to their subcutaneous administration. Therefore, it is unclear whether thromboprophylaxis represents an additional significant burden for MM patients because of the method of administration or adverse bleeding events.
* Main research question What is the current real-life bleeding incidence in MM patients receiving thromboprophylaxis and what is the perceived burden of thromboprophylaxis?
* Design (including population, confounders/outcomes) This prospective observational study will include newly diagnosed MM patients receiving thromboprophylaxis. The International Society on Thrombosis and Haemostasis (ISTH) bleeding criteria and the ISTH bleeding assessment tool (ISTH-BAT) will be adapted to the daybook format, patient friendly vocabulary and translated to Dutch. Patients will be asked to record bleeding events for 6 months after starting thromboprophylaxis. Incidence of bleeding events stratified per major, minor and CRNMB will be calculated with death as competing risk. Bleeding events in LMWH and aspirin patients will be compared with a double-sided z test for independent proportions. Quality of life will be assessed with validated questionnaires. Lastly incidence of VTE and arterial thrombosis (AT) will be calculated.
* Expected results In an RCT comparing LMWH with aspirin prophylaxis for a fracture of an extremity, bleeding events occurred in 14% of patients receiving aspirin and 14% of patients receiving LMWH within 90 days of follow-up. Since comparable doses will be used in this study, we expect to see similar results.

Primary Outcome Measures: Cumulative bleeding incidence with death as competing risk, Bleeding events stratified according to International Society on Thrombosis and Haemostasis (ISTH) criteria: minor bleeding, clinically relevant non-major bleeding and/or major bleeding., 6 months after inclusion
Secondary Outcome Measures: Cumulative venous thrombosis incidence with death as competing risk, VTE events incidence, 6 months after inclusion|Cumulative arterial thrombosis incidence with death as competing risk, AT events incidence, 6 months after inclusion|Quality of life according to the EQ-5D-5L questionnaire, Perceived quality of life according to the EQ-5D-5L questionnaire. This questionnaire assesses quality of life on a scale of 1 to 5 (no problems to severe problems) on five dimensions, namely mobility, self-care, usual activities, pain/discomfort, anxiety/depression. It also measures overall perceived quality of life on a scale of 1 to 100 (the worst health imaginable to the best health imaginable)., Baseline and 6 months after inclusion|Therapy satisfaction according to the PACT-Q questionnaire, Perceived anticoagulation satisfaction according to the PACT-Q questionnaire. The questionnaire evaluates treatment expectations (at baseline), convenience, burden, treatment satisfaction (all three after completion of treatment) on a scale of 1 to 5 (not at all to extremely)., Baseline and 6 months after inclusion