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VWDMin: Minimize Menorrhagia in Women With Von Willebrand Disease

Sponsor
Margaret Ragni (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02606045
Collaborator
University of North Carolina (Other), Duke University (Other)
60
Enrollment
19
Locations
2
Arms
42.2
Anticipated Duration (Months)
3.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an outpatient, 24-week Phase III prospective, randomized, crossover trial comparing recombinant von Willebrand factor (rVWF) and tranexamic acid (TA, Lysteda®) to minimize menorrhagia in women with von Willebrand disease (VWD). The purpose of this Phase III multicenter prospective, randomized, crossover arm trial is to compare recombinant von Willebrand factor (rVWF) to tranexamic acid (TA) in reducing the severity of menorrhagia in women with von Willebrand disease.

Condition or Disease Intervention/Treatment Phase
  • Drug: recombinant von Willebrand factor
  • Drug: tranexamic acid
 Phase 3

Detailed Description

In this study, women age 13-45 years with mild to moderate VWD and menorrhagia will be enrolled at their hemophilia treatment centers (HTCs) and provide information on menstrual bleeding from their two past monthly cycles to establish baseline bleeding frequency. Only women with regular menses, defined as menses every 21-35 days will be enrolled. A total of 60 subjects will be recruited and enrolled at approximately 25 HTC sites. Following enrollment, subjects will be randomized to Group I or Group II for the first five days of the next four consecutive menstrual cycles. Those randomized to Group I will be treated with Arm A for menstrual bleeding in cycles 1 and 2, followed by Arm B for menstrual bleeding in cycles 3 and 4. Those randomized to Group II will be treated with Arm B for menstrual bleeding in cycles 1 and 2, followed by Arm A for menstrual bleeding in cycles 3 and 4.

Subjects randomized to Group I will receive Arm A rVWF 40 IU/kg intravenously (IV) infusion on day 1 of each of two menstrual cycles, Cycles 1 and 2. They will then be crossed over to Arm B, TA 650 mg 2 tablets orally (po) three times daily on days 1-5 of each of two menstrual cycles, Cycles 3 and 4. Subjects randomized to Group II will receive Arm B, TA 650 mg 2 tablets orally (po) three times daily on days 1-5, for each of two menstrual cycles, Cycles 1 and 2. They will then be crossed over to Arm A, rVWF 40 IU/kg intravenously (IV) infusion on day 1 on each of two menstrual cycles, Cycles 3 and 4. This regimen may be given at the HTC clinic or at home by visiting nurse. Baseline laboratory studies will be drawn at screening, including Blood Counts: hemoglobin, white count, differential, platelets; Iron Tests: iron, total iron binding capacity (TIBC), ferritin; Thyroid Test: thyroid stimulating hormone (TSH); and Von Willebrand Tests (VWF and related tests). Before initiating treatment, subjects will be trained by the HTC nurse on 1) reading urine pregnancy tests and 2) completion of the pictorial blood assessment chart (PBAC), cycle severity score (CSR), and cycle length (CL); and 3) completion of patient diary. Following randomization, subjects will administer home pregnancy tests prior to the first of each 5-day dosing cycle. On each of the four dosing cycles, Cycles 1-4, the PBAC, CSR, and CL will be recorded daily. After completion of study drug on cycle 2, the Crossover Study Visit will occur, during which subjects will be given a new supply of study drug for the study arm to which they will crossed over; subject diaries will be returned and coagulation studies and quality of life questionnaires performed. At 10-14 days after completion of study drug in Cycle 4, the End Study Visit will occur, during which subject diaries will be returned and quality of life questionnaires performed. All study visits will be within +/- 2 days of the scheduled visit. Study visits will be every 2 months, at the end of cycle 2 (cross-over) and at the end of cycle 4 (end of study) during which treatment diaries will be reviewed for bleeding frequency, side effects, and medications. Menstrual bleeding by PBAC, cycle severity, cycle duration, and health-related quality-of-life (HRQoL) questionnaires, including Rand Short Form 36-Question Health Survey (SF-36), Ruta Menorrhagia Severity Scale, Center for Disease Control Health-Related Quality of Life-14 Question Form (CDC-HRQoL14), and Center for Epidemiologic Studies Depression Scale (CES-D) will be assessed at baseline and after cycle 2 and after cycle 4. The study is innovative in the 1) evaluation of recombinant VWF, a new high purity recombinant VWF protein, to reduce menorrhagia, as compared with the current non-hormonal standard, tranexamic acid (TA); 2) investigation of the relationship of VWF to menstrual bleeding by PBAC score, by assessing VWD parameters: VWF ristocetin co-factor (VWF:RCo), VWF antigen (VWF:Ag), FVIII:C, VWF multimers, including high molecular weight multimers (HMW) by electrophoresis, and VWF genotype; 3) use of a "home treatment injection" for VWD; 4) comparison of two quality of life measures to assess treatment response on each study arm, one specific for bleeding disorders and one specific for menstrual disorders.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Prospective, Randomized, Crossover Trial Comparing Recombinant Von Willebrand Factor (rVWF) vs. Tranexamic Acid (TA) to Minimize Menorrhagia in Women With Von Willebrand Disease: The VWD Minimize Study
Actual Study Start Date :
Feb 7, 2019
Anticipated Primary Completion Date :
Aug 15, 2022
Anticipated Study Completion Date :
Aug 15, 2022

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Group I

Subjects randomized to Group I will receive Arm A recombinant von Willebrand factor 40 IU/kg intravenously (IV) infusion on day 1 of each of two menstrual cycles, Cycles 1 and 2. They will then be crossed over to Arm B, tranexamic acid 650 mg 2 tablets orally (po) three times daily on days 1-5 of each of two menstrual cycles, Cycles 3 and 4.

Drug: recombinant von Willebrand factor
Group I will receive Arm A recombinant von Willebrand factor 40 IU/kg intravenously (IV) infusion on day 1 of each of two menstrual cycles, Cycles 1 and 2. They will then be crossed over to Arm B, TA 650 mg 2 tablets orally (po) three times daily on days 1-5 of each of two menstrual cycles, Cycles 3 and 4. Group II will receive Arm B, TA 650 mg 2 tablets orally (po) three times daily on days 1-5, for each of two menstrual cycles, Cycles 1 and 2. They will then be crossed over to Arm A, rVWF 40 IU/kg intravenously (IV) infusion on day 1 on each of two menstrual cycles, Cycles 3 and 4.
Other Names:
  • vonicog alfa
  • Vonvendi

    • Drug: tranexamic acid
    Group I will receive Arm A recombinant von Willebrand factor 40 IU/kg intravenously (IV) infusion on day 1 of each of two menstrual cycles, Cycles 1 and 2. They will then be crossed over to Arm B, TA 650 mg 2 tablets orally (po) three times daily on days 1-5 of each of two menstrual cycles, Cycles 3 and 4. Group II will receive Arm B, TA 650 mg 2 tablets orally (po) three times daily on days 1-5, for each of two menstrual cycles, Cycles 1 and 2. They will then be crossed over to Arm A, rVWF 40 IU/kg intravenously (IV) infusion on day 1 on each of two menstrual cycles, Cycles 3 and 4.
    Other Names:
  • Lysteda®

    		•
    Active Comparator: Group II

    Group II will receive Arm B, tranexamic acid 650 mg 2 tablets orally (po) three times daily on days 1-5, for each of two menstrual cycles, Cycles 1 and 2. They will then be crossed over to Arm A, recombinant von Willebrand factor 40 IU/kg intravenously (IV) infusion on day 1 on each of two menstrual cycles, Cycles 3 and 4.

    Drug: recombinant von Willebrand factor
    Group I will receive Arm A recombinant von Willebrand factor 40 IU/kg intravenously (IV) infusion on day 1 of each of two menstrual cycles, Cycles 1 and 2. They will then be crossed over to Arm B, TA 650 mg 2 tablets orally (po) three times daily on days 1-5 of each of two menstrual cycles, Cycles 3 and 4. Group II will receive Arm B, TA 650 mg 2 tablets orally (po) three times daily on days 1-5, for each of two menstrual cycles, Cycles 1 and 2. They will then be crossed over to Arm A, rVWF 40 IU/kg intravenously (IV) infusion on day 1 on each of two menstrual cycles, Cycles 3 and 4.
    Other Names:
  • vonicog alfa
  • Vonvendi

    • Drug: tranexamic acid
    Group I will receive Arm A recombinant von Willebrand factor 40 IU/kg intravenously (IV) infusion on day 1 of each of two menstrual cycles, Cycles 1 and 2. They will then be crossed over to Arm B, TA 650 mg 2 tablets orally (po) three times daily on days 1-5 of each of two menstrual cycles, Cycles 3 and 4. Group II will receive Arm B, TA 650 mg 2 tablets orally (po) three times daily on days 1-5, for each of two menstrual cycles, Cycles 1 and 2. They will then be crossed over to Arm A, rVWF 40 IU/kg intravenously (IV) infusion on day 1 on each of two menstrual cycles, Cycles 3 and 4.
    Other Names:
  • Lysteda®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Menstrual Bleeding Severity [24 weeks]

      Bleeding severity measured by pictorial bleeding assessment chart (PBAC).

    Secondary Outcome Measures

    1. Menstrual bleeding unresponsive to study drugs [24 weeks]

      Menorrhagia cycle severity rating by patient diary, cycle length by PBAC, drug logs

    2. Quality of life including depression, wellness, activity [24 weeks]

      Quality of life questionnaires (HRQoL): Rand Short Form 36-Question Health Survey (SF-36), Ruta Menorrhagia Score, Center for Disease Control Health-Related Quality of Life 14 Questions (CDC-HRQoL-14), and Center for Epidemiology Studies Depression Scale (CES-D), and Satisfaction Survey

    3. von Willebrand assays, genotype [24 weeks]

      von Willebrand assays: VWF ristocetin cofactor (VWF:RCo), VWF antigen ( VWF:Ag), VIII:C, multimers; VWF genotype

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    13 Years to 45 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Adult females 13-45 years of age.

    2. Mild or moderate von Willebrand disease (VWF:RCo <0.50 IU/ml, normal multimers, past bleeding)

    3. Menorrhagia defined as PBAC >100 in at least one of the last two menstrual cycles.

    4. Regular menses, at least every 21-35 days.

    5. Willingness to have blood drawn

    6. No prior history of an allergic reaction or anaphylaxis to rVWF or TA.

    7. Willingness to avoid aspirin (ASA) and nonsteroidal anti-inflammatory agents (NSAIDS) during the study.

    8. Willingness to comply with randomization to rVWF or TA study arms.

    9. Willingness to keep a personal diary of menorrhagia bleeding frequency duration and severity by pictorial blood assessment chart, and any drugs or hemostatic agents taken.

    10. Willingness to make 4 visits and undergo blood sampling for coagulation studies, and accept randomization of two therapies for each of four consecutive menstrual cycles, including an end-of-study visit.

    11. Willingness to use "double-barrier" method of contraception during the study.

    Exclusion Criteria:

    1. Any bleeding disorder other than von Willebrand disease; or past thrombotic disease

    2. Pregnant or lactating, or use of hormones (other than progesterone-only), or combined oral contraceptives, and contraceptive implants in past 3 months.

    3. Platelet count < 100,000/ul.

    4. Use of immunomodulatory or experimental drugs.

    5. Surgery within the past 8 weeks.

    6. Concomitant use of antiplatelet drugs, anticoagulants, dextran, aspirin or NSAIDs.

    7. Treatment with DDAVP, cryoprecipitate, whole blood, plasma and plasma derivatives containing VWF within 5 days of study.

    8. Inability to comply with study requirements.

    9. Hypothyroidism as defined by elevated TSH.

    10. Iron deficiency as defined by low serum ferritin, unless iron replacement has been initiated.

    11. History of renal disease

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Banner MD Anderson Cancer Center Gilbert Arizona United States 85234
    2 Center for Inherited Blood Disorders (CIBD) Orange California United States 92868
    3 University of California San Francisco San Francisco California United States 94117
    4 Emory University Afflac Blood Disorders Center Atlanta Georgia United States 30322
    5 Henry Ford Hospital Medical Center Detroit Michigan United States 48202
    6 Michigan State University East Lansing Michigan United States 48824
    7 Mayo Clinic Rochester Minnesota United States 55902
    8 Washington University St. Louis Saint Louis Missouri United States 63110
    9 Cure4thekids Foundation Las Vegas Nevada United States 89135
    10 Rutgers Robert Wood Johnson Medical School New Brunswick New Jersey United States 08901
    11 State University of New York Upstate Medical Center Syracuse New York United States 13210
    12 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    13 Ohio State University Wexner Medical Center Columbus Ohio United States 43210
    14 Oregon Health and Science University Portland Oregon United States 97239
    15 University of Pittsburgh and Hemophilia Center Western PA Pittsburgh Pennsylvania United States 15213
    16 Vanderbilty University Nashville Tennessee United States 37322
    17 University of Utah Salt Lake City Utah United States 84132
    18 Bloodworks Northwest Seattle Washington United States 98104
    19 Versiti Blood Center of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • Margaret Ragni
    • University of North Carolina
    • Duke University

    Investigators

    • Principal Investigator: Margaret V Ragni, MD, MPH, University of Pittsburgh

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Margaret Ragni, Professor of Medicine, University of Pittsburgh
    ClinicalTrials.gov Identifier:
    NCT02606045
    Other Study ID Numbers:
    • STUDY19030221
    First Posted:
    Nov 17, 2015
    Last Update Posted:
    Mar 2, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Margaret Ragni, Professor of Medicine, University of Pittsburgh
    menorrhagia
    VWD
    Additional relevant MeSH terms:
    Menorrhagia
    Von Willebrand Diseases
    Tranexamic Acid

    Study Results

    No Results Posted as of Mar 2, 2022