NCT02606045

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
39

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Feb 2019

Typical duration for phase_3

Geographic Reach
1 country

19 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 5, 2015

Completed
12 days until next milestone

First Posted

Study publicly available on registry

November 17, 2015

Completed
3.2 years until next milestone

Study Start

First participant enrolled

February 7, 2019

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2022

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 30, 2022

Completed
1.8 years until next milestone

Results Posted

Study results publicly available

July 1, 2024

Completed
Last Updated

July 1, 2024

Status Verified

June 1, 2024

Enrollment Period

3.2 years

First QC Date

November 5, 2015

Results QC Date

March 4, 2024

Last Update Submit

June 27, 2024

Conditions

Keywords

menorrhagiaVWD

Outcome Measures

Primary Outcomes (1)

  • Menstrual Bleeding Severity

    As measured by Pictorial Blood Assessment Chart (PBAC), 0- no theoretical limit, higher score means greater severity

    4 weeks.

Secondary Outcomes (6)

  • Cycle Duration

    4 weeks.

  • Ruta Menorrhagia Severity Scale

    4 weeks.

  • Center for Epidemiology Studies Depression Scale (CES-D)

    4 weeks.

  • Rand Short Form 36-Question Health Survey (SF-36)

    4 weeks

  • Center for Disease Control Health-Related Quality of Life 14 Questions (CDC-HRQoL-14)

    4 weeks.

  • +1 more secondary outcomes

Study Arms (2)

Group I

ACTIVE COMPARATOR

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 factorDrug: tranexamic acid

Group II

ACTIVE COMPARATOR

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 factorDrug: tranexamic acid

Interventions

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.

Also known as: vonicog alfa, Vonvendi
Group IGroup II

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.

Also known as: Lysteda®
Group IGroup II

Eligibility Criteria

Age13 Years - 45 Years
Sexfemale
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Adult females 13-45 years of age.
  • Mild or moderate von Willebrand disease (VWF:RCo \<0.50 IU/ml, normal multimers, past bleeding)
  • Menorrhagia defined as PBAC \>100 in at least one of the last two menstrual cycles.
  • Regular menses, at least every 21-35 days.
  • Willingness to have blood drawn
  • No prior history of an allergic reaction or anaphylaxis to rVWF or TA.
  • Willingness to avoid aspirin (ASA) and nonsteroidal anti-inflammatory agents (NSAIDS) during the study.
  • Willingness to comply with randomization to rVWF or TA study arms.
  • 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.
  • 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.
  • Willingness to use "double-barrier" method of contraception during the study.

You may not qualify if:

  • Any bleeding disorder other than von Willebrand disease; or past thrombotic disease
  • Pregnant or lactating, or use of hormones (other than progesterone-only), or combined oral contraceptives, and contraceptive implants in past 3 months.
  • Platelet count \< 100,000/ul.
  • Use of immunomodulatory or experimental drugs.
  • Surgery within the past 8 weeks.
  • Concomitant use of antiplatelet drugs, anticoagulants, dextran, aspirin or NSAIDs.
  • Treatment with DDAVP, cryoprecipitate, whole blood, plasma and plasma derivatives containing VWF within 5 days of study.
  • Inability to comply with study requirements.
  • Hypothyroidism as defined by elevated TSH.
  • Iron deficiency as defined by low serum ferritin, unless iron replacement has been initiated.
  • History of renal disease

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Center for Inherited Blood Disorders (CIBD)

Orange, California, 92868, United States

Location

University of California San Francisco

San Francisco, California, 94117, United States

Location

Emory University Afflac Blood Disorders Center

Atlanta, Georgia, 30322, United States

Location

Henry Ford Hospital Medical Center

Detroit, Michigan, 48202, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Washington University St. Louis

St Louis, Missouri, 63110, United States

Location

Cure4thekids Foundation

Las Vegas, Nevada, 89135, United States

Location

Rutgers Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

State University of New York Upstate Medical Center

Syracuse, New York, 13210, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh and Hemophilia Center Western PA

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilty University

Nashville, Tennessee, 37322, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Bloodworks Northwest

Seattle, Washington, 98104, United States

Location

Versiti Blood Center of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

  • Ragni MV, Machin N, Malec LM, James AH, Kessler CM, Konkle BA, Kouides PA, Neff AT, Philipp CS, Brambilla DJ. Von Willebrand factor for menorrhagia: a survey and literature review. Haemophilia. 2016 May;22(3):397-402. doi: 10.1111/hae.12898. Epub 2016 Feb 4.

    PMID: 26843404BACKGROUND
  • Ragni MV, Rothenberger SD, Feldman R, Nance D, Leavitt AD, Malec L, Kulkarni R, Sidonio R Jr, Kraut E, Lasky J, Pruthi R, Angelini D, Philipp C, Hwang N, Wheeler AP, Seaman C, Machin N, Xavier F, Meyer M, Bellissimo D, Humphreys G, Smith KJ, Merricks EP, Nichols TC, Ivanco D, Vehec D, Koerbel G, Althouse AD. Recombinant von Willebrand factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von Willebrand disease in the USA (VWDMin): a phase 3, open-label, randomised, crossover trial. Lancet Haematol. 2023 Aug;10(8):e612-e623. doi: 10.1016/S2352-3026(23)00119-9. Epub 2023 Jun 26.

MeSH Terms

Conditions

von Willebrand DiseasesMenorrhagia

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, InheritedBlood Coagulation DisordersHematologic DiseasesHemic and Lymphatic DiseasesCoagulation Protein DisordersBlood Platelet DisordersHemorrhagic DisordersGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesUterine HemorrhageUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesHemorrhagePathologic ProcessesPathological Conditions, Signs and SymptomsMenstruation Disturbances

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic AcidsAcids, CarbocyclicCarboxylic AcidsOrganic Chemicals

Results Point of Contact

Title
Margaret V. Ragni, MD, PHD
Organization
University of Pittsburgh

Study Officials

  • Margaret V Ragni, MD, MPH

    University of Pittsburgh

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

November 5, 2015

First Posted

November 17, 2015

Study Start

February 7, 2019

Primary Completion

April 30, 2022

Study Completion

August 30, 2022

Last Updated

July 1, 2024

Results First Posted

July 1, 2024

Record last verified: 2024-06

Data Sharing

IPD Sharing
Will share

The IPD to be shared include individual bleeding data (PBAC), cycle severity score (CSR), cycle length (CL), quality of life by four scales (SF-36, Ruta, CDC-HRQoL-14, CES-D), satisfaction survey, VWF assays, VWF genotype.

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
Time Frame
Within 12 months of trial completion.
Access Criteria
Qualified investigators will have access to data and bio specimens, consistent with data sharing policies and applicable laws, and upon receipt of a Research Materials Distribution Agreement, data will be transferred by secure transfers through the BioLINCC website.

Locations