Von Willebrand Factor in Pregnancy (VIP) Study

NCT04146376 | Recruiting DMC

• 1 other identifier: STUDY00016309
• Study Type: observational
• Target: 110
• Locations: 1 country
• Sites: 11

Brief Summary

In pregnant women with von Willebrand disease (VWD) who by the third trimester do not have von Willebrand factor (VWF) or factor VIII (FVIII) levels greater than 50-100%, specific guidance is lacking for delivery planning in terms of how high of a VWF level should be achieved to reduce bleeding. This is a prospective, open-label, cohort study in women with VWD using Wilate VWF replacement therapy to maintain trough or minimum VWF levels of 100-150% for delivery and the immediate postpartum period, followed by levels of 50-100% for 5-10 days after delivery, depending upon the route of delivery. The primary objective is to document the rate of primary postpartum hemorrhage (PPH). The secondary objective is to document further effectiveness outcomes and safety.

Conditions

Von Willebrand Diseases

Keywords

von Willebrand Disease; von Willebrand Factor; postpartum hemorrhage

Outcome Measures

Primary Outcomes (1)

• rate of primary postpartum hemorrhage (PPH)

  defined as the estimated and/or quantified blood loss greater than or equal to 1000 mL within 24 hours postpartum; unplanned transfusion of blood products related to blood loss in the first 24 hours postpartum. As a subset of primary PPH, severe primary PPH is defined as the estimated and/or quantified blood loss greater than or equal to 1500 mL and/or requirement of greater than 2 units packed red blood cells within 24 hours postpartum; primary PPH greater than 1000 mL and evidence of maternal hemodynamic instability (tachycardia, hypotension) and/or end organ damage with no other etiology (oliguria, creatinine greater than 0.8, etc.)

  within 24 hours postpartum

Secondary Outcomes (1)

• rate of secondary postpartum hemorrhage (PPH)

  24 hours to 6 weeks postpartum

Other Outcomes (3)

• occurrence of venous or arterial thrombus

  up to 42 days postpartum

• occurrence of infusion-related reactions

  up to 42 days postpartum

• laboratory assessment of efficacy and VWF replacement

  up to 42 days postpartum

Study Arms (2)

Non-Corrector

Patients with gestational week 34-38 von Willebrand factor activity, or von Willebrand factor ristocetin cofactor, or Factor VIII procoagulant activity less than 100 percent will be termed non-correctors. When laboratory monitoring can be performed, patients with an isolated von Willebrand factor collagen binding type 2 defect, von Willebrand factor collagen binding less than 100 percent can also be enrolled and determined as a non-corrector.

Other: Use of a postpartum diary and additional blood draws; Drug: VWF replacement therapy with Wilate; Drug: Tranexamic acid

Corrector

Patients with von Willebrand factor parameter levels greater than or equal to 100 percent self-corrected at gestational weeks 34-38 will be termed correctors.

Drug: Tranexamic acid; Other: Use of a postpartum diary and additional blood draws.

Interventions

Use of a postpartum diary and additional blood draws. OTHER

A diary will be used to capture postpartum hemorrhage (PPH), tranexamic acid use, other drug use, bleeding episodes, and treatment schedules. Several blood draws additional to what is expected for routine clinical care will also be taken.

Corrector

VWF replacement therapy with Wilate DRUG

This study design uses on-label Wilate for VWF replacement therapy for delivery and the postpartum period in VWD patients whose VWF levels are \<100% in the third trimester of pregnancy

Non-Corrector

Tranexamic acid DRUG

This study design uses tranexamic acid for prophylaxis for postpartum hemorrhage for all women with VWD

Corrector; Non-Corrector

Eligibility Criteria

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

Study Population

The investigators or qualified research personnel will approach all consecutive pregnant VWD patients. Patients who meet all of the inclusion criteria and none of the exclusion criteria are eligible for this study.

You may qualify if:

• von Willebrand Disease (VWD) patients defined prepartum as Type 1 per National Heart, Lung, and Blood Institute (NHLBI) criterion of von Willebrand Factor (VWF) level less than 30 percent, or Type 2, or Type 3 VWD
• A diagnosis of VWD and VWF and Factor VIII (FVIII) levels obtained in gestational weeks 34-38 that determine enrollment in the non-corrector group:
• Patients with gestational week 34-38 VWF:Ag, VWF:Act (or VWF:RCo), or FVIII:C less than 100 percent will be enrolled in the non-corrector group. In patients with an isolated VWF:CB type 2 defect, VWF:CB less than 100 percent can also be determined as a non-corrector
• Patients with all VWF parameter levels greater than or equal to 100 percent self-corrected at gestational weeks 34-38 will be enrolled in the corrector group
• Written informed consent from the patient prepartum, before gestational week 39

You may not qualify if:

• Presence of a clinical contraindication to receive wilate or tranexamic acid, as determined by the health care provider, such as a prior drug reaction
• Presence of other concurrent disorder of hemostasis, platelet dysfunction, or collagen disorders
• Presence of liver disease or renal disease, clinical suspicion or diagnosis of preeclampsia or eclampsia, HELLP syndrome, TTP, DIC, or other acquired vasculopathy or coagulopathy
• Age less than 18 years
• Inability of the local laboratory to monitor the VWF laboratory tests needed during the course of treatment to determine Wilate dosing adjustments

Sponsors & Collaborators

• University of Washington: lead
• Ergomed: collaborator
• Octapharma: collaborator

Study Sites (11)

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Emory University

Atlanta, Georgia, 30308, United States

RECRUITING

Bleeding & Clotting Disorders Institute

Peoria, Illinois, 61615, United States

RECRUITING

Tulane University School of Medicine, Louisiana Center for Bleeding and Clotting Disorders

New Orleans, Louisiana, 70112, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

WITHDRAWN

The Pennsylvania State University

Hershey, Pennsylvania, 17033, United States

RECRUITING

Vanderbilt University

Nashville, Tennessee, 27232, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84108, United States

RECRUITING

Washington Center for Bleeding Disorders

Seattle, Washington, 98104, United States

RECRUITING

Related Publications (18)

• James AH, Konkle BA, Kouides P, Ragni MV, Thames B, Gupta S, Sood S, Fletcher SK, Philipp CS. Postpartum von Willebrand factor levels in women with and without von Willebrand disease and implications for prophylaxis. Haemophilia. 2015 Jan;21(1):81-7. doi: 10.1111/hae.12568. Epub 2014 Oct 21.

  PMID: 25333737 BACKGROUND

• Drury-Stewart DN, Lannert KW, Chung DW, Teramura GT, Zimring JC, Konkle BA, Gammill HS, Johnsen JM. Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy. PLoS One. 2014 Nov 19;9(11):e112935. doi: 10.1371/journal.pone.0112935. eCollection 2014.

  PMID: 25409031 BACKGROUND

• Kouides PA. Present day management of inherited bleeding disorders in pregnancy. Expert Rev Hematol. 2016 Oct;9(10):987-95. doi: 10.1080/17474086.2016.1216312. Epub 2016 Aug 2.

  PMID: 27459638 BACKGROUND

• Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009 Dec;114(6):1326-1331. doi: 10.1097/AOG.0b013e3181c2bde8.

  PMID: 19935037 BACKGROUND

• Szecsi PB, Jorgensen M, Klajnbard A, Andersen MR, Colov NP, Stender S. Haemostatic reference intervals in pregnancy. Thromb Haemost. 2010 Apr;103(4):718-27. doi: 10.1160/TH09-10-0704. Epub 2010 Feb 19.

  PMID: 20174768 BACKGROUND

• Huq FY, Kulkarni A, Agbim EC, Riddell A, Tuddenham E, Kadir RA. Changes in the levels of factor VIII and von Willebrand factor in the puerperium. Haemophilia. 2012 Mar;18(2):241-5. doi: 10.1111/j.1365-2516.2011.02625.x. Epub 2011 Sep 28.

  PMID: 21951573 BACKGROUND

• Nichols WL, Hultin MB, James AH, Manco-Johnson MJ, Montgomery RR, Ortel TL, Rick ME, Sadler JE, Weinstein M, Yawn BP. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia. 2008 Mar;14(2):171-232. doi: 10.1111/j.1365-2516.2007.01643.x.

  PMID: 18315614 BACKGROUND

• Demers C, Derzko C, David M, Douglas J; Society of Obstetricians and Gynecologists of Canada. Gynaecological and obstetric management of women with inherited bleeding disorders. J Obstet Gynaecol Can. 2005 Jul;27(7):707-32. doi: 10.1016/s1701-2163(16)30551-5. English, French.

  PMID: 16100628 BACKGROUND

• Mannucci PM, Franchini M, Castaman G, Federici AB; Italian Association of Hemophilia Centers. Evidence-based recommendations on the treatment of von Willebrand disease in Italy. Blood Transfus. 2009 Apr;7(2):117-26. doi: 10.2450/2008.0052-08.

  PMID: 19503633 BACKGROUND

• Laffan MA, Lester W, O'Donnell JS, Will A, Tait RC, Goodeve A, Millar CM, Keeling DM. The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology. Br J Haematol. 2014 Nov;167(4):453-65. doi: 10.1111/bjh.13064. Epub 2014 Aug 12. No abstract available.

  PMID: 25113304 BACKGROUND

• Stoof SC, van Steenbergen HW, Zwagemaker A, Sanders YV, Cannegieter SC, Duvekot JJ, Leebeek FW, Peters M, Kruip MJ, Eikenboom J. Primary postpartum haemorrhage in women with von Willebrand disease or carriership of haemophilia despite specialised care: a retrospective survey. Haemophilia. 2015 Jul;21(4):505-12. doi: 10.1111/hae.12635. Epub 2015 Feb 16.

  PMID: 25688733 BACKGROUND

• Hawke L, Grabell J, Sim W, Thibeault L, Muir E, Hopman W, Smith G, James P. Obstetric bleeding among women with inherited bleeding disorders: a retrospective study. Haemophilia. 2016 Nov;22(6):906-911. doi: 10.1111/hae.13067. Epub 2016 Oct 5.

  PMID: 27704714 BACKGROUND

• Janssen CA, Scholten PC, Heintz AP. A simple visual assessment technique to discriminate between menorrhagia and normal menstrual blood loss. Obstet Gynecol. 1995 Jun;85(6):977-82. doi: 10.1016/0029-7844(95)00062-V.

  PMID: 7770270 BACKGROUND

• James AH, Jamison MG. Bleeding events and other complications during pregnancy and childbirth in women with von Willebrand disease. J Thromb Haemost. 2007 Jun;5(6):1165-9. doi: 10.1111/j.1538-7836.2007.02563.x.

  PMID: 17403089 BACKGROUND

• Kirtava A, Drews C, Lally C, Dilley A, Evatt B. Medical, reproductive and psychosocial experiences of women diagnosed with von Willebrand's disease receiving care in haemophilia treatment centres: a case-control study. Haemophilia. 2003 May;9(3):292-7. doi: 10.1046/j.1365-2516.2003.00756.x.

  PMID: 12694520 BACKGROUND

• Govorov I, Lofgren S, Chaireti R, Holmstrom M, Bremme K, Mints M. Postpartum Hemorrhage in Women with Von Willebrand Disease - A Retrospective Observational Study. PLoS One. 2016 Oct 25;11(10):e0164683. doi: 10.1371/journal.pone.0164683. eCollection 2016.

  PMID: 27780267 BACKGROUND

• James AH, Cooper DL, Paidas MJ. A global quantitative survey of hemostatic assessment in postpartum hemorrhage and experience with associated bleeding disorders. Int J Womens Health. 2017 Jul 3;9:477-485. doi: 10.2147/IJWH.S132135. eCollection 2017.

  PMID: 28740434 BACKGROUND

• Kujovich JL. von Willebrand disease and pregnancy. J Thromb Haemost. 2005 Feb;3(2):246-53. doi: 10.1111/j.1538-7836.2005.01150.x. No abstract available.

  PMID: 15670029 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma collection for coagulation parameters Whole blood collection for DNA and RNA analysis Cord blood sample

MeSH Terms

Conditions

von Willebrand Diseases; Postpartum Hemorrhage

Interventions

von Willebrand Factor; 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)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Jill M Johnsen, M.D.

  University of Washington

  PRINCIPAL INVESTIGATOR

• Barbara A Konkle, M.D.

  Washington Center for Bleeding Disorders

  PRINCIPAL INVESTIGATOR

• Peter A Kouides, M.D.

  Mary M. Gooley Hemophilia Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Central Study Contact

CONTACT

919-792-3740; VIP.Study@ergomedgroup.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, School of Medicine: Hematology and Oncology

Study Record Dates

• First Submitted: October 29, 2019
• First Posted: October 31, 2019
• Study Start: October 12, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)