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The EMPOWER trial is a pilot multi-center, placebo-controlled (normal saline), double-blind (patient and outcome assessor), crossover, 2-year randomized trial in female outpatients with von Willebrand disease (VWD) and heavy menstrual bleeding to determine trial feasibility and viability, and to explore assay sensitivity of the proposed efficacy clinical outcomes for a definitive randomized controlled trial
The EMPOWER trial is a pilot multi-center, placebo-controlled (normal saline), double-blind (patient and outcome assessor), crossover, 2-year randomized trial in female outpatients with von Willebrand disease (VWD) and heavy menstrual bleeding to determine trial feasibility and viability, and explore assay sensitivity of the proposed efficacy clinical outcomes for a definitive randomized controlled trial.
For the first treatment period, patients will be randomized to receive either plasma derived von Willebrand factor:Factor VIII (pdVWF:FVIII) concentrate (plus standard of care) or placebo (plus standard of care) for VWD-associated heavy menstrual bleeding for 4 cycles, crossing over to the comparator treatment during the second treatment period. The first treatment period will be followed by a 1 cycle washout period when no study-based treatment will be delivered.
The main purpose of the pilot will be to evaluate viability and feasibility of the trial design, as well as to explore assay sensitivity to inform determination of the primary efficacy outcome for the definitive randomized trial which will evaluate the effect of prophylaxis with pdVWF:FVIII concentrate compared with placebo on HMB in women with VWD. A secondary objective is to conduct a preliminary assessment of the effect on clinical outcomes of 2-3 doses of prophylaxis with pdVWF:FVIII concentrate when provided on the first 4 days of menstruation compared with placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| pdVWF:FVIII concentrate (Wilate®) Treatment and Standard Care | Experimental | Wilate® at a dose of 30-60 IU VWF:RCo/kg for the two anticipated heaviest days of bleeding every 24-48 hours within the first 4 days of menstruation will be provided. Additional two optional doses 24-48 hours from the last can be provided. A minimum of 2 doses must be provided. |
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| Placebo and Standard Care | Placebo Comparator | Patients randomized to the placebo arm will receive intravenous placebo (normal saline) at the same approximate volume and frequency as the study drug. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lyophilized concentrate of human coagulation von Willebrand Factor and factor VIII | Drug | Wilate® is a plasma-derived, highly purified concentrate administered through intravenous injection. Wilate® contains an average VWF ristocetin cofactor activity to FVIII activity at ratio of 1:1. |
| Measure | Description | Time Frame |
|---|---|---|
| Blinding Index (BI) score at the end of cycle 4 of treatment period 1 and 2 | Blinding Index (BI) score at the end of cycle 4 of treatment period 1 and 2 | 2 years |
| Proportion of participant drop-out at the end of treatment period 1 and 2 | Proportion of participant drop-out at the end of treatment period 1 and 2 | 2 years |
| Proportion of participants with completed for the candidate primary clinical efficacy outcomes at the end of treatment period 1 and 2 | Proportion of patients with completed for the candidate primary clinical efficacy outcomes at the end of treatment period 1 and 2 | 2 years |
| Number of participants enrolled in 2 years (i.e. ability to enroll at least 10 participants in 2 years) | Ability to enroll at least 10 participants in 2 years | 2 years |
| Proportion of participants with carryover effect for the candidate primary clinical efficacy outcomes from period 1 to period 2 | Proportion of participants with carryover effect for the candidate primary clinical efficacy outcomes from period 1 to period 2 | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Mean of the 3 highest daily Modified PBAC (mPBAC) scores within each individual participant cycle averaged across 4 individual participant cycles at the end of each treatment period | Mean of the 3 highest daily Modified PBAC (mPBAC) scores within each individual participant cycle averaged across 4 individual participant cycles at the end of each treatment period | At the end of 8 menstrual cycles (approximately 10 days) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| St. Michael's Hospital | Contact | 4168646060 | empower@unityhealth.to |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Michael's Hospital | Recruiting | Toronto | Ontario | M5B1W8 | Canada |
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| Placebo | Other | Patients randomized to the placebo arm will receive intravenous normal saline at the same approximate volume and frequency of Wilate ®. |
|
| The proportion of patients who use of rescue therapy at the end of each treatment period | The proportion of patients who use of rescue therapy (i.e. more than two days of oral tranexamic acid use, additional treatment with Wilate®, additional hormonal therapy for HMB, urgent/emergent gynecological surgery for HMB, treatment with intravenous iron, red blood cell transfusion, or hospital admission for HMB) at the end of each treatment period | At the end of 8 menstrual cycles (approximately 10 days) |
| Mean of the mPBAC score within each individual participant cycle averaged across 4 individual participant cycles | Mean of the mPBAC score within each individual participant cycle averaged across 4 individual participant cycles | At the end of 8 menstrual cycles (approximately 10 days) |
| Median of the mPBAC score within each individual participant cycle used to derive the median across 4 individual participant cycles | Median of the mPBAC score within each individual participant cycle used to derive the median across 4 individual participant cycles | At the end of 8 menstrual cycles (approximately 10 days) |
| Number of days of oral tranexamic acid use | Number of days of oral tranexamic acid use | At the end of 8 menstrual cycles (approximately 10 days) |
| Number of days of Wilate® treatment received | Number of days of Wilate® treatment received | At the end of 8 menstrual cycles (approximately 10 days) |
| Duration of menstruation (measured in days) | Duration of menstruation (measured in days) | At the end of 8 menstrual cycles (approximately 10 days) |
| Major bleed according to the International Society on Thrombosis and Haemostasis (ISTH) definition | Major bleed according to the International Society on Thrombosis and Haemostasis (ISTH) definition | At the end of 8 menstrual cycles (approximately 10 days) |
| Clinically relevant non-major bleed | Clinically relevant non-major bleed | At the end of 8 menstrual cycles (approximately 10 days) |
| Hemoglobin levels (g/L) | Hemoglobin levels (g/L) | At the end of 8 menstrual cycles (approximately 10 days) |
| Ferritin levels (mcg/L) | Ferritin levels (mcg/L) | At the end of 8 menstrual cycles (approximately 10 days) |
| Use of additional hormonal therapy for heavy menstrual bleeding | Use of additional hormonal therapy for heavy menstrual bleeding | At the end of 8 menstrual cycles (approximately 10 days) |
| Requirement of urgent/emergent gynecological surgery for heavy menstrual bleeding | Requirement of urgent/emergent gynecological surgery for heavy menstrual bleeding | At the end of 8 menstrual cycles (approximately 10 days) |
| Fatigue scores (as measured by the FACIT fatigue scale) | Fatigue scores (as measured by the FACIT fatigue scale) | At the end of 8 menstrual cycles (approximately 10 days) |
| Short Form-12 Scores | Short Form-12 Scores | At the end of 8 menstrual cycles (approximately 10 days) |
| Scores on the individual components of the Short Form-12 | Scores on the individual components of the Short Form-12 | At the end of 8 menstrual cycles (approximately 10 days) |
| Requirement of hemostatic care (tranexamic acid, Wilate®, platelet transfusion) | Requirement of hemostatic care (tranexamic acid, Wilate®, platelet transfusion) | At the end of 8 menstrual cycles (approximately 10 days) |
| Requirement of anemia focused care (intravenous iron and/or red blood cell transfusion) | Requirement of anemia focused care (intravenous iron and/or red blood cell transfusion) | At the end of 8 menstrual cycles (approximately 10 days) |
| Number of hypersensitivity infusion reactions | Number of hypersensitivity infusion reactions | At the end of 8 menstrual cycles (approximately 10 days) |
| Number of thromboembolic events (defined as symptomatic or incidental, suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); | Number of thromboembolic events (defined as symptomatic or incidental, suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); | At the end of 8 menstrual cycles (approximately 10 days) |
| Proportion of participants who development of VWF inhibitors | Proportion of participants who development of VWF inhibitors | At the end of 8 menstrual cycles (approximately 10 days) |
| Number of adverse events | Number of adverse events | 8 cycles |
| ID | Term |
|---|---|
| D014842 | von Willebrand Diseases |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020147 | Coagulation Protein Disorders |
| D001791 | Blood Platelet Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| D005169 | Factor VIII |
| D014841 | von Willebrand Factor |
| ID | Term |
|---|---|
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011498 | Protein Precursors |
| D001685 | Biological Factors |
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