OC 60.3 - Prevention of Hemorrhage After Implantation of Mechanical Circulatory Support With a Purified Von Willebrand Factor Concentrate: results of the early terminated randomized controlled PHAM trial

Tuesday, June 27, 2023

15:15 – 15:30 ET

Room: 516

Session Available As: Live-Stream and On-Demand

Presenting Author(s)

Antoine Rauch (he/him/his)

Associate Professor
Univ.Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France
Lille, Nord-Pas-de-Calais, France

Co-Author(s)

GL

Guillaume Lebreton

MD, PhD
Groupe Hospitalier La Pitié Salpêtrière-Charles Foix, 55577, Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Paris, France
Paris, Ile-de-France, France
MM

Mouhamed D Moussa

MD
Pôle d’Anesthésie-Réanimation, CHU Lille, F59000, Lille, France.
Lille, Nord-Pas-de-Calais, France
AV

André Vincentelli

MD, PhD
Cardiac Surgery, Lille Hospital University, 59000, Lille, France
Lille, Nord-Pas-de-Calais, France
EF

Erwan Flecher

MD, PhD
Department of Thoracic and Cardiovascular Surgery, Pontchaillou University Hospital, University of Rennes 1, Signal and Image Treatment Laboratory (LTSI), Inserm U1099, Rennes, France.
Rennes, Bretagne, France
OB

Olivier Bouchot

MD, PhD
Department of Cardiac Surgery, Dijon University Hospital, 21000 Dijon, France
Dijon, Bourgogne, France
CD

Camille Dambrin

MD, PhD
Department of Thoracic and Cardiovascular Surgery, Rangueil University Hospital, Toulouse, France
Toulouse, Midi-Pyrenees, France
BR

Bertrand Rozec

MD, PhD
Cardiothoracic and Cardiovascular Intensive Care Unit, Laennec University Hospital, Saint-Herblain, France
Nantes, Pays de la Loire, France
LB

Laurent Barandon

MD, PhD
Cardiovascular Surgery Department, Haut-Lévêque Hospital, CHU Bordeaux, Pessac, France
Bordeaux, Aquitaine, France
EJ

Emmanuelle Jeanpierre

PharmD
Lille University Hospital, Hematology Transfusion, 59000, Lille, France
LILLE, Nord-Pas-de-Calais, France
NA

Nadine Ajzenberg

MD, PhD
Laboratoire d'Hématologie, AP-HP, Hôpital Bichat Claude-Bernard, Paris, France.
Paris, Ile-de-France, France
Yohann Repessé, MD-PhD (he/him/his)

MD, PhD
CRC-MHC Caen
Caen, Basse-Normandie, France
ED

Emmanuel De Maistre

MD
Hématologie Biologique, CHU, Dijon
Dijon, Bourgogne, France
EB

Elodie Boissier

PharmD
Laboratoire d'Hématologie, Hôpital Laënnec, CHU de Nantes, France
Nantes, Pays de la Loire, France
David Smadja, PhD (he/him/his)

Professor of hematology
Université Paris Cité, Ile-de-France, France
FN

Fabienne Nedelec-Gac

PharmD
Department of Hematology/Hemostasis, Pontchaillou University Hospital of Rennes, Rennes, France
Rennes, Bretagne, France
SV

Sophie Voisin

PharmD
Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Toulouse, Midi-Pyrenees, France
SL

Silvy Laporte

PharmD, PhD
Department of Clinical Pharmacology and Clinical Research Unit, University Hospital of Saint-Etienne; UMR 1059 DVH-Sainbiose, Jean Monnet University, Saint-Etienne; INSERM F-CRIN INNOVTE Network France
Saint Etienne, Rhone-Alpes, France
JL

Julien Labreuche

MD, PhD
Department of Biostatistics, CHU Lille, University of Lille, France
Lille, Nord-Pas-de-Calais, France
Sophie Susen, MD, PhD (she/her/hers)

MD, PhD
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
Lille, Nord-Pas-de-Calais, France

Background: Bleeding complications often occur in patients with left ventricular assist device (LVAD). The high shear stress in LVAD leads to increased proteolysis von Willebrand factor (VWF) in plasma which may contribute to this high bleeding rate. Whether the prophylactic administration of a VWF concentrate could reduce bleeding rate in LVAD-patients has never been evaluated.

Aims: To determine the efficacy, safety and pharmacokinetic (PK) of VWF prophylaxis in LVAD-setting

Methods: PHAM is a multicenter randomized controlled trial (NCT02488525) investigating the efficacy, safety and PK of a plasma-derived VWF concentrate almost devoid of FVIII (Wilfactin®), administered prophylactically twice a week at 50 IU/kg for 3 months after LVAD-implantation, in comparison to usual care. Patients were randomized between day-4 and day-7 after LVAD-implantation, once VWF defect confirmed. The efficacy endpoints were the difference in the rate of any, clinically significant or major bleeding (according to ISTH criteria). Bleeding and thrombotic events were reviewed at day-7, day-14 and then once every 2 weeks until end of follow-up. The study was terminated early due to deficient recruitment and drug shortage. We present the available data.

Results: Thirty adult patients were randomized. VWF prophylaxis resulted in a non-significant 55% relative risk reduction in bleeding rate compared to standard of care management (risk ratio, 0.45; 95% CI, 0.18 to 1.04; p=0.062; Figure). Accordingly, there was a trend for a reduction in clinically relevant/major bleeding and transfusion needs in VWF arm (Table). Severe adverse events were similar between VWF and control arms including deaths (n=2 and n=4 respectively) and thrombotic events (2 each, potentially related to Wilfactin® in VWF arm). In the PK analysis, a rapid clearance of VWF product occurred within 24 hours following the first infusion.

Conclusion(s): This study suggests at best a transient and mild effect of VWF prophylaxis in LVAD-setting due to an early clearance of VWF concentrate

Learning Objectives:

Left ventricular assist device support is associated with an acquired von Willebrand factor (VWF) defect that could contribute to an increased risk of bleeding
This study shows at best a transient and mild effect of VWF prophylaxis on bleeding pattern in LVAD-setting (off-label)
This study shows a rapide clearance of VWF oncentrates when administered in LVAD-setting (off-label)