A phase III study comparing secondary long-term prophylaxis versus on-demand treatment with vWF/FVIII concentrates in severe inherited von Willebrand disease

Flora Peyvandi, Giancarlo Castaman, Paolo Gresele, Raimondo De Cristofaro, Piercarla Schinco, Antonella Bertomoro, Massino Morfini, Gabriella Gamba, Giovanni Barillari, Víctor Jiménez-Yuste, Cristoph Königs, Alfonso Iorio, Augusto B. Federici

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)391-398
Number of pages8
JournalBlood transfusion = Trasfusione del sangue
Volume17
Issue number5
DOIs
Publication statusPublished - Sep 1 2019

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Hematology

Cite this

Peyvandi, F., Castaman, G., Gresele, P., De Cristofaro, R., Schinco, P., Bertomoro, A., Morfini, M., Gamba, G., Barillari, G., Jiménez-Yuste, V., Königs, C., Iorio, A., & Federici, A. B. (2019). A phase III study comparing secondary long-term prophylaxis versus on-demand treatment with vWF/FVIII concentrates in severe inherited von Willebrand disease. Blood transfusion = Trasfusione del sangue, 17(5), 391-398. https://doi.org/10.2450/2019.0183-18