Von Willebrand Factor in Pregnancy (VIP) Study

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Use of a postpartum diary and additional blood draws
  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.
• Препарат VWF replacement therapy with Wilate
  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
• Препарат Tranexamic acid
  This study design uses tranexamic acid for prophylaxis for postpartum hemorrhage for all women with VWD
• Другое Use of a postpartum diary and additional blood draws.
  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.

Первичные конечные точки

• rate of primary postpartum hemorrhage (PPH) [Срок оценки: within 24 hours postpartum]

Вторичные конечные точки (1)

• rate of secondary postpartum hemorrhage (PPH) [Срок оценки: 24 hours to 6 weeks postpartum]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 11 центров

• University of Colorado — Aurora
• Yale University — New Haven
• University of Miami — Miami
• Emory University — Atlanta
• Bleeding & Clotting Disorders Institute — Peoria
• Tulane University School of Medicine, Louisiana Center for Bleeding and Clotting Disorders — New Orleans
• Oregon Health & Science University — Portland
• The Pennsylvania State University — Hershey
• … и ещё 3 центра

Публикации

• James AH, Konkle BA, Kouides P, Ragni MV, Thames B, Gupta S, Sood S, Fletcher SK, Philipp CS. Postpartum von Willebrand factor levels in women with and without von Willebrand disease and implications for prophylaxis. Haemophilia. 2015 Jan;21(1):81-7. doi: 10.1111/hae.12568. Epub 2014 Oct 21. PMID 25333737
• Drury-Stewart DN, Lannert KW, Chung DW, Teramura GT, Zimring JC, Konkle BA, Gammill HS, Johnsen JM. Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy. PLoS One. 2014 Nov 19;9(11):e112935. doi: 10.1371/journal.pone.0112935. eCollection 2014. PMID 25409031
• Kouides PA. Present day management of inherited bleeding disorders in pregnancy. Expert Rev Hematol. 2016 Oct;9(10):987-95. doi: 10.1080/17474086.2016.1216312. Epub 2016 Aug 2. PMID 27459638
• Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009 Dec;114(6):1326-1331. doi: 10.1097/AOG.0b013e3181c2bde8. PMID 19935037
• Szecsi PB, Jorgensen M, Klajnbard A, Andersen MR, Colov NP, Stender S. Haemostatic reference intervals in pregnancy. Thromb Haemost. 2010 Apr;103(4):718-27. doi: 10.1160/TH09-10-0704. Epub 2010 Feb 19. PMID 20174768
• Huq FY, Kulkarni A, Agbim EC, Riddell A, Tuddenham E, Kadir RA. Changes in the levels of factor VIII and von Willebrand factor in the puerperium. Haemophilia. 2012 Mar;18(2):241-5. doi: 10.1111/j.1365-2516.2011.02625.x. Epub 2011 Sep 28. PMID 21951573
• Nichols WL, Hultin MB, James AH, Manco-Johnson MJ, Montgomery RR, Ortel TL, Rick ME, Sadler JE, Weinstein M, Yawn BP. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia. 2008 Mar;14(2):171-232. doi: 10.1111/j.1365-2516.2007.01643.x. PMID 18315614
• Demers C, Derzko C, David M, Douglas J; Society of Obstetricians and Gynecologists of Canada. Gynaecological and obstetric management of women with inherited bleeding disorders. J Obstet Gynaecol Can. 2005 Jul;27(7):707-32. doi: 10.1016/s1701-2163(16)30551-5. English, French. PMID 16100628

Идентификаторы

NCT: NCT04146376 · STUDY00016309

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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