Von Willebrand Factor in Pregnancy (VIP) Study: A Multicenter Study of Wilate Use in Von Willebrand Disease for Childbirth
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- Bloodworks
- 入组人数
- 110
- 试验地点
- 11
- 主要终点
- rate of primary postpartum hemorrhage (PPH)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •Presence of a clinical contraindication to receive wilate or tranexamic acid, as determined by the health care provider, such as a prior drug reaction
- •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
研究组 & 干预措施
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.
干预措施: Use of a postpartum diary and additional blood draws (Other)
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.
干预措施: VWF replacement therapy with Wilate (Drug)
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.
干预措施: Tranexamic acid (Drug)
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.
干预措施: Tranexamic acid (Drug)
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.
干预措施: Use of a postpartum diary and additional blood draws. (Other)
结局指标
主要结局
rate of primary postpartum hemorrhage (PPH)
时间窗: 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.)
次要结局
- rate of secondary postpartum hemorrhage (PPH)(24 hours to 6 weeks postpartum)
研究者
Jill Johnsen
Associate Member, Bloodworks Northwest Research Institute
Bloodworks