Von Willebrand Factor in Pregnancy (VIP) Study
- Conditions
- Von Willebrand Diseases
- Interventions
- Other: Use of a postpartum diary and additional blood drawsDrug: VWF replacement therapy with WilateOther: Use of a postpartum diary and additional blood draws.
- Registration Number
- NCT04146376
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 110
- 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
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Non-Corrector VWF replacement therapy with Wilate 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. Corrector Use of a postpartum diary and additional blood draws. 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. Non-Corrector Use of a postpartum diary and additional blood draws 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. Corrector Tranexamic acid 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. Non-Corrector Tranexamic acid 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.
- Primary Outcome Measures
Name Time Method rate of primary postpartum hemorrhage (PPH) within 24 hours postpartum 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.)
- Secondary Outcome Measures
Name Time Method rate of secondary postpartum hemorrhage (PPH) 24 hours to 6 weeks postpartum excessive blood loss: any transfusions not anticipated in the antepartum birth plan and unrelated to a primary PPH, including number and type of blood component units (blood products, red blood cells, plasma, platelets, cryoprecipitate) transfused within 48 hours after diagnosis and management; any transfusions not anticipated in the antepartum birth plan and unrelated to a primary PPH, including number and type of blood component units (blood products, red blood cells, plasma, platelets, cryoprecipitate) transfused beyond 48 hours after diagnosis and management; change in antepartum hemoglobin; change in pictorial blood assessment chart (PBAC) score; number of patients needing pharmacologic or surgical 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
Trial Locations
- Locations (11)
University of Colorado
🇺🇸Aurora, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
University of Miami
🇺🇸Miami, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Bleeding & Clotting Disorders Institute
🇺🇸Peoria, Illinois, United States
Tulane University School of Medicine, Louisiana Center for Bleeding and Clotting Disorders
🇺🇸New Orleans, Louisiana, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
The Pennsylvania State University
🇺🇸Hershey, Pennsylvania, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Washington Center for Bleeding Disorders
🇺🇸Seattle, Washington, United States