Clinical trial NCT04146376: Von Willebrand Factor in Pregnancy (VIP) Study
Official title: Von Willebrand Factor in Pregnancy (VIP) Study: a Multicenter Study of Wilate Use in Von Willebrand Disease for Childbirth
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Von Willebrand Diseases
Keywords: von Willebrand Disease
von Willebrand Factor
postpartum hemorrhage
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Ergomed
name: Octapharma
First posted: 2019-10-31
Enrollment: 110
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility 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 VWD

or

* 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

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

Primary outcomes:
measure: rate of primary postpartum hemorrhage (PPH)
timeFrame: within 24 hours postpartum
Secondary outcomes:
measure: rate of secondary postpartum hemorrhage (PPH)
timeFrame: 24 hours to 6 weeks postpartum
Other outcomes:
measure: occurrence of venous or arterial thrombus
timeFrame: up to 42 days postpartum
measure: occurrence of infusion-related reactions
timeFrame: up to 42 days postpartum
measure: laboratory assessment of efficacy and VWF replacement
timeFrame: up to 42 days postpartum
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Peoria
country: United States
facility: Bleeding & Clotting Disorders Institute
state: Illinois
city: New Orleans
country: United States
facility: Tulane University School of Medicine, Louisiana Center for Bleeding and Clotting Disorders
state: Louisiana
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hershey
country: United States
facility: The Pennsylvania State University
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Washington Center for Bleeding Disorders
state: Washington
Study officials:
affiliation: University of Washington
name: Jill M Johnsen, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington Center for Bleeding Disorders
name: Barbara A Konkle, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mary M. Gooley Hemophilia Center
name: Peter A Kouides, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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