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Phase 3 study of recombinant von Willebrand factor in patients with severe von Willebrand disease who are undergoing elective surgery
Author(s) -
Peyvandi F.,
Mamaev A.,
Wang J.D.,
Stasyshyn O.,
Timofeeva M.,
Curry N.,
Cid A. R.,
Yee T. T.,
Kavakli K.,
Castaman G.,
Sytkowski A.
Publication year - 2019
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14313
Subject(s) - medicine , von willebrand disease , von willebrand factor , thromboelastometry , hemostasis , surgery , coagulopathy , platelet
SummaryEssentials Recombinant von Willebrand factor (rVWF) is effective in von Willebrand disease (VWD). A phase 3 study of rVWF, with/without recombinant factor VIII (rFVIII) before surgery in VWD. Overall rVWF's efficacy was rated excellent/good; rVWF was administered alone in most patients. rVWF was well‐tolerated and hemostasis was achieved in patients with severe VWD undergoing surgery.Summary Background Recombinant von Willebrand factor ( rVWF ) has demonstrated efficacy for on‐demand treatment of bleeding in severe von Willebrand disease ( VWD ), warranting evaluation in the surgical setting. Objectives This study ( NCT 02283268) evaluated the hemostatic efficacy/safety profile of rVWF , with/without recombinant factor VIII ( rFVIII ), in patients with severe VWD undergoing surgery. Patients/Methods Patients received rVWF 40–60 IU kg −1 , VWF ristocetin cofactor activity was measured 12–24 h before surgery. If endogenous FVIII activity ( FVIII :C) target levels were achieved 3 h before surgery, rVWF was administered alone 1 h before surgery; rVWF was co‐administered with rFVIII if target endogenous FVIII levels were not achieved. rVWF was infused postoperatively to maintain target trough levels. Overall and intraoperative hemostatic efficacy, the pharmacodynamics of rVWF administration and the incidence of adverse events ( AE s) were assessed. Results All patients treated with rVWF for major ( n = 10), minor ( n = 4) and oral ( n = 1) surgery had overall and intraoperative hemostatic efficacy ratings of excellent (73.3% and 86.7%) or good (26.7% and 13.3%). Most rVWF infusions (89.4%) were administered alone, resulting in hemostatically effective levels of endogenous FVIII within 6 h, which were sustained for 72–96 h; 70% ( n = 7/10) of major surgeries were performed without rFVIII co‐administration. Six patients reported 12 treatment‐emergent AE s. Two patients each had one serious AE : diverticulitis (not treatment related) and deep vein thrombosis (sponsor‐assessed as possibly treatment related). No severe allergic reactions or inhibitory antibodies were reported. Conclusions These data support the efficacy and safety profile of rVWF in patients with severe VWD undergoing elective surgery.