Prevent Postpartum Hemorrhage in Women With Von Willebrand Disease: The VWD-WOMAN Trial

NCT04344860 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: STUDY20030186
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center randomized phase III clinical trial, the VWD-Woman Trial, in which 20 pregnant subjects with von Willebrand disease (VWD), defined as VWF ristocetin co-factor activity (VWF:RCo) \<0.50 IU/ml (historic) and previous history of bleeding are enrolled. Subjects will include women with VWD age 18 years and older, excluding those who have a bleeding disorder other than VWD. Once enrolled, subjects who meet all of the inclusion and none of the exclusion criteria will be randomized to recombinant Von Willebrand factor (rVWF, Vonvendi ®) with Tranexamic Acid (TA, Cyclokapron®); or recombinant Von Willebrand factor (rVWF, Vonvendi®) alone to prevent postpartum hemorrhage after vaginal or caesarean delivery. The primary endpoint is quantitative blood loss (QBL) by a labor suite nurse at delivery. Secondary endpoints include safety assessment for postpartum lochial blood loss by Pictorial Blood Assessment Chart (PBAC), transfusion, blood products, thromboembolic events, and hysterectomy within 21 days; and mechanism of PPH reduction by VWF assays (VWF:RCo, VWF:Ag, VIII:C), fibrinogen, and d-dimer. Blood draws are at 5 time points, including at 36 weeks' gestation (screening), on admission for childbirth, and at 1 day, 2 days, and 21 days after delivery. The VWD-Woman Trial is considered greater than minimal risk as study drugs are given at delivery and special coagulation studies are obtained.

Conditions

Von Willebrand Diseases; Postpartum Hemorrhage

Outcome Measures

Primary Outcomes (1)

• Volume of Quantitative Blood Loss at Delivery

  Blood loss at delivery by standard QBL measured for 6 hours postpartum by the labor and delivery nursing staff.

  6hrs

Secondary Outcomes (3)

• Blood Loss Postpartum by Pictorial Bleeding Assessment Chart (PBAC)

  21 days

• Number of Blood Products Used

  21 days

• Concentration of Von Willebrand Factor

  21 days

Study Arms (2)

rVWF plus TA

ACTIVE COMPARATOR

Subjects randomized to this arm will receive recombinant von Willebrand factor 80 IU/kg IV within 5-10 minutes of delivery (or epidural anesthesia) plus Tranexamic Acid 1 gm IV within 3 hours of delivery; and recombinant Von Willebrand factor 80 IU/kg on day 1 and day 2 postpartum.

Drug: Recombinant Von Willebrand factor; Drug: Tranexamic Acid Injection [Cyklokapron]

rVWF alone

ACTIVE COMPARATOR

Subjects randomized to this arm will receive recombinant von Willebrand factor 80 IU/kg IV within 5-10 minutes of delivery (or epidural anesthesia); and recombinant Von Willebrand factor 80 IU/kg on day 1 and day 2 postpartum.

Drug: Recombinant Von Willebrand factor

Interventions

Recombinant Von Willebrand factor DRUG

Recombinant Von Willebrand factor(Vonvendi) is an intravenous therapy that replaces missing VWF to restore hemostasis and reduce bleeding with surgery or delivery.

Also known as: rVWF, Vonvendi

rVWF alone; rVWF plus TA

Tranexamic Acid Injection [Cyklokapron] DRUG

Tranexamic acid (Cyclokapron) is an intravenous anti-fibrinolytic therapy that prevents clot breakdown and reduces bleeding with surgery or delivery.

Also known as: TA, Cyclokapron

rVWF plus TA

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pregnant females \>= 18 years of age
• Confirmed VWD, as defined by VWF:RCo \< 0.50 IU/dL and previous history of bleeding
• Willingness to have blood drawn
• Willing to be randomized to one of two treatments at delivery and for 2 days postpartum.
• Willing to keep a diary for 3 weeks of postpartum bleeding by pictorial assessment chart (PBAC) and any blood products, transfusion, or medications taken.
• Willing to return at 21 days for final blood draw and review of diary.

You may not qualify if:

• Any bleeding disorder other than VWD; or past thrombotic disease of other bleeding disorders.
• Previous thrombosis, cardiac disease, congestive failure, arrhythmia, hypertension, MI, or stroke.
• Platelet count \< 100,000/ ul.
• Past allergic reaction to VWF or tranexamic acid.
• Surgery within the past 8 weeks.
• Inability to comply with study protocol requirements.
• Concomitant use of antiplatelet drugs, anticoagulants, or NSAIDs. Aspirin will be allowed for preeclampsia prevention.
• Treatment with DDAVP, cryoprecipitate, whole blood, plasma or plasma derivatives containing substantial quantities of VWF within 5 days of study.
• History of renal disease.
• Inability to comply with study requirements.

Sponsors & Collaborators

• Nicoletta C Machin: lead

Study Sites (1)

Hemophilia Center of Western PA

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (4)

• Ragni MV, Machin N, James AH, Seaman CD, Malec LM, Kessler CM, Konkle BA, Kouides PA, Neff AT, Philipp CS, Brooks MM. Feasibility of the Von Willebrand disease PREVENT trial. Thromb Res. 2017 Aug;156:8-13. doi: 10.1016/j.thromres.2017.05.022. Epub 2017 May 25.

  PMID: 28577390 BACKGROUND

• Ragni MV. Blood volume-based von Willebrand factor to prevent postpartum hemorrhage in von Willebrand disease. Blood Adv. 2017 Apr 25;1(11):703-706. doi: 10.1182/bloodadvances.2017005090. eCollection 2017 Apr 25.

  PMID: 29296713 BACKGROUND

• Ragni MV. Case-based discussion on the implications of exogenous estrogens in hemostasis and thrombosis: the hematologist's view. Hematology Am Soc Hematol Educ Program. 2019 Dec 6;2019(1):152-157. doi: 10.1182/hematology.2019000022.

  PMID: 31808846 BACKGROUND

• Machin NC, Brooks MM, Vehec D, Ivanco D, Lawryk B, Seaman CD, Xavier F, Shiva S, Verdoni A, Ragni MV. Impact of tranexamic acid on postpartum hemorrhage in type 1 von Willebrand disease treated with recombinant VWF. Blood Adv. 2025 Dec 9;9(23):6031-6039. doi: 10.1182/bloodadvances.2025017046.

  PMID: 40902088 DERIVED

MeSH Terms

Conditions

von Willebrand Diseases; Postpartum Hemorrhage

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Blood Platelet Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Limitations and Caveats

There are several limitations of this study. First, the small sample size and pilot nature of this study restrict the generalizability of the findings. Further, as findings in type 1 VWD may not predict those with more severe disease, future studies should include pregnant females with type 2 and 3 VWD.

Results Point of Contact

• Title: Nicoletta Machin
• Organization: University Of Pittsburgh

machinnc2@upmc.edu

(412) 209-7280

Study Officials

• Nicoletta Machin, DO

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: Randomized, Controlled Trial

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: April 14, 2020
• Study Start: June 4, 2021
• Primary Completion: August 28, 2024
• Study Completion: September 1, 2024
• Last Updated: October 31, 2025
• Results First Posted: October 31, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• 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 biospecimens, consistent with data sharing policies and applicable laws, and upon receipt of a Research Materials Distribution Agreement, data will be transferred by secure transfer through the GSPH portal website.

Locations

US (1)