Prevent Postpartum Hemorrhage in Women With Von Willebrand Disease: The VWD-WOMAN Trial
Paraules clau
Resum
Descripció
The purpose of this 8-week single center, randomized, open-label phase III trial to compare recombinant von Willebrand factor (rVWF, Vonvendi®)) plus tranexamic acid (TA, Cyclokapron®) vs. rVWF alone to prevent postpartum hemorrhage (PPH) in women with Von Willebrand disease (VWD). VWD is an inherited bleeding disorder that occurs in 1% of the population. It is caused by deficient or defective von Willebrand factor (VWF). Treatment at delivery is with VWF concentrate, based on U.S. and European guidelines, and as DDAVP, a non-VWF protein, is contraindicated as it may cause hyponatremia (low salt) and seizures due to fluid replacement at delivery. Yet, blood loss is 1.5-fold greater in VWD than non-VWD controls. The investigators believe this is due to physiologic (protective) fibrinolysis (clot breakdown) in the first 3 hours after delivery, which may protect controls from excess clotting after delivery, but which may increase bleeding in subjects with VWD. PPH a significant cause of maternal morbidity and mortality in women. PPH is defined as >1000 ml within the first 24 hours of vaginal or cesarean delivery. PPH peaks in the first 2-3 hours postpartum, a time during which there is early activation of the fibrinolytic system, with a 2-fold increase TPA (tissue plasminogen activator). So while uterine atony is the major cause of PPH, accounting for 63% of PPH cases, but in 37% of cases, uterotonic agents fail.
TA is an anti-fibrinolytic therapy (prevents clot breakdown) which reduces bleeding and prevents clot breakdown in surgery, trauma, and in controls at delivery, if it is given within 3 hours of delivery. In the WOMAN trial, a large trial of over 10,000 women without bleeding disorders, TA was safe and effective in reducing PPH when given intravenously (in a vein) within 3 hours of vaginal or cesarean delivery. As TA is approved by the US. Food and Drug Administration (FDA) to treat and prevent bleeding in VWD, the investigators propose to study rVWF plus TA vs. VWF alone to reduce PPH in subjects with VWD. This is a pilot study to determine if recruitment, randomization, and study drug administration can be performed successfully, and shows preliminary safety and efficacy in subjects with VWD. rVWF (Vonvendi®) will be administered by intravenous infusion before delivery and on day 1 and day 2 postpartum. Tranexamic acid (Cyclokapron®) will be administered by intravenous infusion within 3 hours postpartum. Randomization will be at delivery to either rVWF at delivery and on day 1 and day 2 postpartum, plus TA within three hours postpartum; or rVWF alone at delivery and on day 1 and day 2 postpartum.
Dates
| Darrera verificació: | 05/31/2020 |
| Primer enviat: | 04/08/2020 |
| Inscripció estimada enviada: | 04/08/2020 |
| Publicat per primera vegada: | 04/13/2020 |
| Última actualització enviada: | 06/17/2020 |
| Publicació de l'última actualització: | 06/18/2020 |
| Data d'inici de l'estudi real: | 08/31/2020 |
| Data estimada de finalització primària: | 08/30/2021 |
| Data estimada de finalització de l’estudi: | 09/29/2021 |
Condició o malaltia
Intervenció / tractament
Drug: Recombinant Von Willebrand factor
Drug: rVWF plus TA
Fase
Grups de braços
| Braç | Intervenció / tractament |
|---|---|
| Active Comparator: rVWF plus TA Subjects randomized to this arm will receive recombinant von Willebrand factor 80 IU/kg IV within 5-10 minutes of delivery (or epidural anesthesia) plus Tranexamic Acid 1 gm IV within 3 hours of delivery; and recombinant Von Willebrand factor 80 IU/kg on day 1 and day 2 postpartum. | Drug: rVWF plus TA Tranexamic acid (Cyclokapron) is an intravenous anti-fibrinolytic therapy that prevents clot breakdown and reduces bleeding with surgery or delivery. |
| Active Comparator: rVWF alone Subjects randomized to this arm will receive recombinant von Willebrand factor 80 IU/kg IV within 5-10 minutes of delivery (or epidural anesthesia); and recombinant Von Willebrand factor 80 IU/kg on day 1 and day 2 postpartum. |
Criteris d'elegibilitat
| Edats elegibles per estudiar | 18 Years Per a 18 Years |
| Sexes elegibles per estudiar | Female |
| Accepta voluntaris saludables | Sí |
| Criteris | Inclusion Criteria: 1. Pregnant females > 18 years of age 2. Confirmed VWD, as defined by VWF:RCo < 0.50 IU/dL and previous history of bleeding 3. Willingness to have blood drawn 4. Willing to be randomized to one of two treatments at delivery and for 2 days postpartum. 5. Willing to keep a diary for 3 weeks of postpartum bleeding by pictorial assessment chart (PBAC) and any blood products, transfusion, or medications taken. 6. Willing to return at 21 days for final blood draw and review of diary. Exclusion Criteria: 1. Any bleeding disorder other than VWD; or past thrombotic disease of other bleeding disorders. 2. Previous thrombosis, cardiac disease, congestive failure, arrhythmia, hypertension, MI, or stroke. 3. Platelet count < 100,000/ ul. 4. Past allergic reaction to VWF or tranexamic acid. 5. Surgery within the past 8 weeks. 6. Inability to comply with study protocol requirements. 7. Concomitant use of antiplatelet drugs, anticoagulants, aspirin or NSAIDs. 8. Treatment with DDAVP, cryoprecipitate, whole blood, plasma or plasma derivatives containing substantial quantities of VWF within 5 days of study. 9. History of renal disease. 10. Inability to comply with study requirements. |
Resultat
Mesures de resultats primaris
1. Volume of quantitative blood loss at delivery [1 day]
Mesures de resultats secundaris
1. Volume of lochia blood loss [21 days]
2. Number of blood products used [21 days]
3. Concentration of von Willebrand factor [21 days]
