Von Willebrand Factor in Pregnancy (VIP) Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Von Willebrand Factor in Pregnancy (VIP) Study: A Multicenter Study of Wilate Use in Von Willebrand Disease for Childbirth

Conditions
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Von Willebrand Diseases

Intervention / Treatment
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* 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.


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non-Corrector<br>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<br>* 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.<br>Drug: VWF replacement therapy with Wilate<br>* 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<br>Drug: Tranexamic acid<br>* This study design uses tranexamic acid for prophylaxis for postpartum hemorrhage for all women with VWD<br>|
| Corrector<br>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<br>* This study design uses tranexamic acid for prophylaxis for postpartum hemorrhage for all women with VWD<br>Other: Use of a postpartum diary and additional blood draws.<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of primary postpartum hemorrhage (PPH) | 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 | within 24 hours postpartum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of secondary postpartum hemorrhage (PPH) | 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 | 24 hours to 6 weeks postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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von Willebrand Disease, von Willebrand Factor, postpartum hemorrhage