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Von Willebrand DiseasesPhase 3NCT04344860

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

A Phase 3 study testing Recombinant Von Willebrand factor and Tranexamic Acid Injection [Cyklokapron] in people with Von Willebrand Diseases and Postpartum Hemorrhage, run by Nicoletta C Machin at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Recombinant Von Willebrand factor and Tranexamic Acid Injection [Cyklokapron]
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
4 Jun 2021to 1 Sep 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 10Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Hemophilia Center of Western PA

    Pittsburgh, Pennsylvania, 15213

Other trials in United States

About this study

Official title: Prospective, Randomized Trial Comparing Recombinant Von Willebrand Factor (rVWF) Plus Tranexamic Acid vs. rVWF Alone to Reduce Postpartum Hemorrhage in Women With Von Willebrand Disease: The VWD-WOMAN Trial

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.

Read the detailed description

The purpose of this 8-week single center, randomized, open-label phase III trial to compare recombinant von Willebrand factor (rVWF, Vonvendi®)) plus tranexamic acid (TA, Cyclokapron®) vs. rVWF alone to prevent postpartum hemorrhage (PPH) in women with Von Willebrand disease (VWD). VWD is an inherited bleeding disorder that occurs in 1% of the population. It is caused by deficient or defective von Willebrand factor (VWF). Treatment at delivery is with VWF concentrate, based on U.S. and European guidelines, and as DDAVP, a non-VWF protein, is contraindicated as it may cause hyponatremia (low salt) and seizures due to fluid replacement at delivery. Yet, blood loss is 1.5-fold greater in VWD than non-VWD controls. The investigators believe this is due to physiologic (protective) fibrinolysis (clot breakdown) in the first 3 hours after delivery, which may protect controls from excess clotting after delivery, but which may increase bleeding in subjects with VWD. PPH a significant cause of maternal morbidity and mortality in women. PPH is defined as >1000 ml within the first 24 hours of vaginal or cesarean delivery. PPH peaks in the first 2-3 hours postpartum, a time during which there is early activation of the fibrinolytic system, with a 2-fold increase TPA (tissue plasminogen activator). So while uterine atony is the major cause of PPH, accounting for 63% of PPH cases, but in 37% of cases, uterotonic agents fail.

TA is an anti-fibrinolytic therapy (prevents clot breakdown) which reduces bleeding and prevents clot breakdown in surgery, trauma, and in controls at delivery, if it is given within 3 hours of delivery. In the WOMAN trial, a large trial of over 10,000 women without bleeding disorders, TA was safe and effective in reducing PPH when given intravenously (in a vein) within 3 hours of vaginal or cesarean delivery. As TA is approved by the US. Food and Drug Administration (FDA) to treat and prevent bleeding in VWD, the investigators propose to study rVWF plus TA vs. VWF alone to reduce PPH in subjects with VWD. This is a pilot study to determine if recruitment, randomization, and study drug administration can be performed successfully, and shows preliminary safety and efficacy in subjects with VWD. rVWF (Vonvendi®) will be administered by intravenous infusion before delivery and on day 1 and day 2 postpartum. Tranexamic acid (Cyclokapron®) will be administered by intravenous infusion within 3 hours postpartum. Randomization will be at delivery to either rVWF at delivery and on day 1 and day 2 postpartum, plus TA within three hours postpartum; or rVWF alone at delivery and on day 1 and day 2 postpartum.

Being tested
Recombinant Von Willebrand factor, Tranexamic Acid Injection [Cyklokapron]
Medical subject headings
von Willebrand Diseases, Postpartum Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Recombinant Von Willebrand factorDrug

    Also called rVWF, Vonvendi

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

  • Tranexamic Acid Injection [Cyklokapron]Drug

    Also called TA, Cyclokapron

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

Study groups in NCT04344860
Study groupRoleWhat they receive
rVWF plus TAActive comparatorSubjects 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.
Receives: Drug: Recombinant Von Willebrand factor; Drug: Tranexamic Acid Injection [Cyklokapron]
rVWF aloneActive comparatorSubjects 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.
Receives: Drug: Recombinant Von Willebrand factor

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6hrs

Secondary outcomes (3)
  1. Blood Loss Postpartum by Pictorial Bleeding Assessment Chart (PBAC)

    Blood loss postpartum by pictorial bleeding assessment chart (PBAC).

    Participants record the degree of saturation of sanitary products and the presence of clots.

    Total PBAC scores range from 0 to >500, with higher scores indicating heavier menstrual bleeding.

    A score ≥100 is conventionally consistent with heavy bleeding.

    Each sanitary product is assigned a score reflecting the amount of blood loss:

    Pads: 1 (point) for lightly stained, 5 for moderately soiled, 20 for fully soaked Tampons: 1 for lightly stained, 5 for moderately soiled, 10 for fully soaked Clots: 1 point for small (<1 cm), 5 for large (>1 cm) Daily scores are summed to produce a total cycle PBAC score. Subscale items (pads and clots) were summed to obtain a total PBAC score.

    Measured: 21 days

  2. Number of Blood Products Used

    Number of transfused blood products determined by electronic medical record review and patient diary.

    Measured: 21 days

  3. Concentration of Von Willebrand Factor

    Plasma levels of von Willebrand Factor antigen (VWF:Ag) and activity (VWF:RCo) measured during the peripartum period. Higher concentrations indicate greater clotting factor activity.

    Measured: 21 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2020
  2. Study start4 Jun 2021
  3. Primary completion28 Aug 2024
  4. Study completion1 Sep 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, Controlled Trial
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04344860
Sponsor's protocol ID
STUDY20030186
Status last verified
Oct 2025
First submitted
9 Apr 2020
Last updated
31 Oct 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The IPD to be shared include individual bleeding data (EBL, PBAC); hemostasis agents (blood product usage, transfusion, other medications); and VWF assays (VWF:RCo, VWF:Ag, FVIII:C) and coagulation assays (fibrinogen, d-dimer).

Publications

  • 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.

    PubMed 28577390
  • 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.

    PubMed 29296713
  • 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.

    PubMed 31808846
  • 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.

    PubMed 40902088

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Recombinant Von Willebrand factor and Tranexamic Acid Injection [Cyklokapron] in people with Von Willebrand Diseases and Postpartum Hemorrhage, run by Nicoletta C Machin at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Volume of Quantitative Blood Loss at Delivery (time frame: 6hrs). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04344860, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2025.

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