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Von Willebrand Factor in Pregnancy (VIP) Study (VIP)

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ClinicalTrials.gov Identifier: NCT04146376
Recruitment Status : Recruiting
First Posted : October 31, 2019
Last Update Posted : January 28, 2021
Sponsor:
Collaborators:
Mary M. Gooley Hemophilia Center
Ergomed
Octapharma
Information provided by (Responsible Party):
Jill Johnsen, Bloodworks

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.


Condition or disease Intervention/treatment
Von Willebrand Diseases Other: Use of a postpartum diary and additional blood draws Drug: VWF replacement therapy with Wilate Drug: Tranexamic acid Other: Use of a postpartum diary and additional blood draws.

Detailed Description:

For pregnant women with von Willebrand disease (VWD) who by the third trimester do not have von Willebrand factor (VWF) or factor VIII (FVIII) levels > 50-100%, specific guidance is lacking for delivery planning for how high a VWF level should be achieved. Specifically, guidance is lacking on whether VWF replacement therapy should target a VWF minimum level in the 100-150% range, i.e., a range closer to the 200-250% levels observed in normal pregnancy.

This is a prospective, open-label, cohort study using Wilate VWF replacement therapy, trough or minimum VWF levels of 100-150% will be maintained for delivery in women with VWD whose third trimester VWF levels are <100%. This group is termed "non-correctors". Women with VWD whose third trimester VWF levels spontaneously rise to >100% will be assigned to the "corrector" group, and these women will not receive VWF replacement therapy. All patients will receive tranexamic acid for 14 days postpartum. Outcome parameters will be assessed for all patients.

The investigators or qualified research personnel will approach all consecutive pregnant VWD patients until 65 non-corrector patients have completed the study protocol, and up to 30 corrector patients have completed the study protocol. Patients with gestational week 34-38 von Willebrand factor activity (VWF:Act) or von Willebrand factor ristocetin cofactor (VWF:RCo), and/or Factor VIII procoagulant activity (FVIII:C) less than 100 percent will be used to assign patients to the non-corrector group. When VWF collagen binding (VWF:CB) laboratory monitoring can be performed, patients with an isolated VWF:CB type 2 defect can also be enrolled.

Rate of primary postpartum hemorrhage, severe postpartum hemorrhage, secondary postpartum hemorrhage will be measured. Safety and secondary laboratory measures will be assessed.

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Study Type : Observational
Estimated Enrollment : 110 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Von Willebrand Factor in Pregnancy (VIP) Study: A Multicenter Study of Wilate Use in Von Willebrand Disease for Childbirth
Actual Study Start Date : October 12, 2019
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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

A diary will be used to capture postpartum hemorrhage (PPH), Wilate and 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.


Drug: VWF replacement therapy with Wilate
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

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

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

Other: Use of a postpartum diary and additional blood draws.

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.





Primary Outcome Measures :
  1. rate of primary postpartum hemorrhage (PPH) [ Time Frame: within 24 hours postpartum ]
    estimated blood loss greater than or equal to 1000 mL, or severe PPH defined as estimated blood loss greater than 2000 mL within 24 hours postpartum, as indicated by: visual estimation, pre- and post- weight of blood soaked materials, photospectrometry


Secondary Outcome Measures :
  1. rate of secondary postpartum hemorrhage (PPH) [ Time Frame: 24 hours to 6 weeks postpartum ]
    excessive blood loss: any transfusions not anticipated in the antepartum birth plan, including number and type of blood products transfused within 48 hours after treatment, any transfusions not anticipated in the antepartum birth plan, including number and type of blood products transfused beyond 48 hours after treatment, change in antepartum hemoglobin, change in pictorial blood assessment chart (PBAC) score, number of patients needing interventions for bleeding (e.g., use of Bakri balloon, angiographic embolization, B-Lynch sutures, surgical arterial ligation, or hysterectomy for persistent bleeding), iron levels (serum iron, TIBC, and ferritin) 6 weeks postpartum


Other Outcome Measures:
  1. occurrence of venous or arterial thrombus [ Time Frame: up to 42 days postpartum ]
    clinically documented venous or arterial thrombus

  2. occurrence of infusion-related reactions [ Time Frame: up to 42 days postpartum ]
    clinically documented infusion-related reactions

  3. laboratory assessment of efficacy and VWF replacement [ Time Frame: up to 42 days postpartum ]
    central laboratory assessment of VWF parameters relative to bleeding


Biospecimen Retention:   Samples With DNA
Plasma collection for coagulation parameters Whole blood collection for DNA and RNA analysis Cord blood sample


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
Criteria

Inclusion Criteria:

  • 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
  • VWF and Factor VIII (FVIII) levels obtained in gestational weeks 34-38 will determine enrollment in the non-corrector or corrector group:
  • Patients with gestational week 34-38 VWF:Ag, VWF:Act (or VWF:RCo), or FVIII:Act 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 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04146376


Contacts
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Contact: Sarah Ruuska, MPH 206-689-6193 sarahru@bloodworksnw.org

Locations
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United States, Illinois
Bleeding & Clotting Disorders Institute Recruiting
Peoria, Illinois, United States, 61615
Contact: Jonathan Roberts, MD    309-692-5337    jroberts@ilbcdi.org   
Principal Investigator: Jonathan Roberts, MD         
United States, Louisiana
Tulane University School of Medicine, Louisiana Center for Bleeding and Clotting Disorders Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Melody Benton, MPH, MAS, CCRP    504-988-3596    mbenton@tulane.edu   
Principal Investigator: Maissaa Janbain, MD         
United States, Washington
Washington Center for Bleeding Disorders at Bloodworks Recruiting
Seattle, Washington, United States, 98104
Contact: Sarah Ruuska, MPH    206-689-6193    sarahru@bloodworksnw.org   
Principal Investigator: Jill Johnsen, MD         
Sponsors and Collaborators
Bloodworks
Mary M. Gooley Hemophilia Center
Ergomed
Octapharma
Investigators
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Principal Investigator: Jill M Johnsen, M.D. Bloodworks
Principal Investigator: Barbara A Konkle, M.D. Bloodworks
Principal Investigator: Peter A Kouides, M.D. Mary M. Gooley Hemophilia Center
Publications:

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Responsible Party: Jill Johnsen, Associate Member, Bloodworks Northwest Research Institute, Bloodworks
ClinicalTrials.gov Identifier: NCT04146376    
Other Study ID Numbers: VIPStudy
First Posted: October 31, 2019    Key Record Dates
Last Update Posted: January 28, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Jill Johnsen, Bloodworks:
von Willebrand Disease
von Willebrand Factor
postpartum hemorrhage
Additional relevant MeSH terms:
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Von Willebrand Diseases
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Blood Platelet Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants