Flora Peyvandi1,2, Giancarlo Castaman3,4, Paolo Gresele5, Raimondo De Cristofaro6, Piercarla Schinco7, Antonella Bertomoro8, Massino Morfini9, Gabriella Gamba10, Giovanni Barillari11, Víctor Jiménez-Yuste12, Cristoph Königs13, Alfonso Iorio14,5, Augusto B Federici15,16. 1. Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, Milan, Italy. 2. Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 3. Haemophilia and Thrombosis Center, "San Bortolo" Hospital, Vicenza, Italy. 4. Centre for Bleeding Disorders and Coagulation, "Careggi" University Hospital, Florence, Italy. 5. Department of Medicine, University of Perugia, Haemophilia Center, Azienda Ospedaliera di Perugia, Perugia, Italy. 6. Haemorrhagic and Thrombotic Diseases Unit, "A. Gemelli" University Hospital Foundation IRCCS, Institute of Internal Medicine and Geriatrics, Catholic University "S. Cuore", Rome, Italy. 7. Regional Reference Center for Hereditary Haemorrhagic and Thrombotic Diseases of Adult Patients, "Le Molinette" Hospital, Turin Italy. 8. Haemophilia Centre, II Clinica Medica, University of Padua, Padua, Italy. 9. Italian Association of Haemophilia Centres, Milan, Italy. 10. Haemophilia Centre and Congenital Coagulopathies Unit,"S. Matteo" University Hospital, Pavia, Italy. 11. Sos Malattie Emorragiche e Trombotiche, Dipartimento di Area Vasta di Medicina Trasfusionale, Presidio Ospedaliero "S. Maria della Misericordia", ASUI di Udine, Udine, Italy. 12. Haematology Department, "La Paz" University Hospital, "Autonoma" University, Madrid, Spain. 13. University Hospital Frankfurt, "Goethe" University, Department of Pediatrics, Frankfurt am Main, Germany. 14. Department of Health Research Methods, Evidence, and Impact and Department of Medicine, McMaster University, Hamilton, Canada. 15. Division of Haematology and Transfusion Medicine, "Luigi Sacco" University Hospital, Milan, Italy. 16. Department of Oncology and Onco-Haematology, University of Milan, Milan, Italy.
Abstract
BACKGROUND: There is a lack of prospective clinical trials specifically designed to evaluate the benefits of prophylaxis with vWF/FVIII concentrates in patients with inherited von Willebrand disease (vWD). The aim of the study was to compare efficacy of secondary long-term prophylaxis (PRO) with vWF/FVIII in the prevention of bleeding episodes in severe vWD patients to standard of care (on-demand treatment; ODT). MATERIALS AND METHODS: In this 12-month, phase III, open-label study (PRO.WILL), vWD patients (aged ≥6 years) were randomised to PRO (n=9; 5 completed) or ODT (n=10; 7 completed) treatment with Fanhdi®/Alphanate® (Grifols) according to current licensing status for use in vWD. We assessed the proportion of patients who did not present any spontaneous bleeding episode, adverse events (AEs) or thrombotic events. RESULTS:All patients on ODT had vWD type 2 or 3 vs 70% of patients on PRO. All ODT patients experienced bleeds vs 60% on PRO. PRO patients showed fewer bleeds (n=32 vs n=172 [112 in the same patient, mostly mucosal]; p<0.0001) and lower risk of bleeding (relative attributable risk estimate: -0.667; 95% CI: -2.374, -0.107; p<0.001). Most frequent bleeds in ODT and PRO groups were, respectively, epistaxis (n=52 vs n=15) and gastrointestinal (n=13 [9 in the same patient] vs n=1). While most bleeds lasted one day under ODT (31/32), only epistaxis did so in PRO group (14/15). No AEs due to study medication were observed. DISCUSSION: Despite the small sample size and the heterogeneity of the study population, patients on vWF/FVIII prophylaxis showed a reduction in bleeding risk and rate compared to on-demand treatment.
RCT Entities:
BACKGROUND: There is a lack of prospective clinical trials specifically designed to evaluate the benefits of prophylaxis with vWF/FVIII concentrates in patients with inherited von Willebrand disease (vWD). The aim of the study was to compare efficacy of secondary long-term prophylaxis (PRO) with vWF/FVIII in the prevention of bleeding episodes in severe vWD patients to standard of care (on-demand treatment; ODT). MATERIALS AND METHODS: In this 12-month, phase III, open-label study (PRO.WILL), vWD patients (aged ≥6 years) were randomised to PRO (n=9; 5 completed) or ODT (n=10; 7 completed) treatment with Fanhdi®/Alphanate® (Grifols) according to current licensing status for use in vWD. We assessed the proportion of patients who did not present any spontaneous bleeding episode, adverse events (AEs) or thrombotic events. RESULTS: All patients on ODT had vWD type 2 or 3 vs 70% of patients on PRO. All ODTpatients experienced bleeds vs 60% on PRO. PRO patients showed fewer bleeds (n=32 vs n=172 [112 in the same patient, mostly mucosal]; p<0.0001) and lower risk of bleeding (relative attributable risk estimate: -0.667; 95% CI: -2.374, -0.107; p<0.001). Most frequent bleeds in ODT and PRO groups were, respectively, epistaxis (n=52 vs n=15) and gastrointestinal (n=13 [9 in the same patient] vs n=1). While most bleeds lasted one day under ODT (31/32), only epistaxis did so in PRO group (14/15). No AEs due to study medication were observed. DISCUSSION: Despite the small sample size and the heterogeneity of the study population, patients on vWF/FVIII prophylaxis showed a reduction in bleeding risk and rate compared to on-demand treatment.
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