Von Willebrand Factor in Pregnancy (VIP) Study

Bloodworks

Status: Unknown

Conditions: Von Willebrand Diseases

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

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT04146376

VIPStudy

Details and patient eligibility

About

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.

Full 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.

Enrollment: 110 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

110 participants in 2 patient groups

Non-Corrector

Description:

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.

Treatment:

Drug: Tranexamic acid

Drug: VWF replacement therapy with Wilate

Other: Use of a postpartum diary and additional blood draws

Corrector

Description:

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.

Treatment:

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

Drug: Tranexamic acid