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

Publications

>

Article

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

Publicated to:Blood Transfusion. 17 (5): 391-398 - 2019-09-01 17(5), DOI: 10.2450/2019.0183-18

Authors: Peyvandi, Flora; Castaman, Giancarlo; Gresele, Paolo; De Cristofaro, Raimondo; Schinco, Piercarla; Bertomoro, Antonella; Morfini, Massino; Gamba, Gabriella; Barillari, Giovanni; Jimenez-Yuste, Victor; Koenigs, Cristoph; Iorio, Alfonso; Federici, Augusto B

Affiliations

ASUI Udine, Presidio Osped S Maria della Misericordia, Dipartimento Area Vasta Med Trasfus, Sos Malattie Emorrag & Trombot, Udine, Italy - Author

Careggi Univ Hosp, Ctr Bleeding Disorders & Coagulat, Florence, Italy - Author

Catholic Univ S Cuore, Inst Internal Med & Geriatr, A Gemelli Univ Hosp Fdn IRCCS, Haemorrhag & Thrombot Dis Unit, Rome, Italy - Author

Goethe Univ, Dept Pediat, Univ Hosp Frankfurt, Frankfurt, Germany - Author

Italian Assoc Haemophilia Ctr, Milan, Italy - Author

Le Molinette Hosp, Reg Reference Ctr Hereditary Haemorrhag & Thrombo, Turin, Italy - Author

Luigi Sacco Univ Hosp, Div Haematol & Transfus Med, Milan, Italy - Author

McMaster Univ, Dept Hlth Res Methods Evidence & Impact, Hamilton, ON, Canada - Author

McMaster Univ, Dept Med, Hamilton, ON, Canada - Author

Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Angelo Bianchi Bonomi Haemophilia & Thrombosis Ct, Via Pace 9, I-20122 Milan, Italy - Author

S Matteo Univ Hosp, Congenital Coagulopathies Unit, Pavia, Italy - Author

S Matteo Univ Hosp, Haemophilia Ctr, Pavia, Italy - Author

San Bortolo Hosp, Haemophilia & Thrombosis Ctr, Vicenza, Italy - Author

Univ Autonoma Madrid, La Paz Univ Hosp, Haematol Dept, Madrid, Spain - Author

Univ Milan, Dept Oncol & Oncohaematol, Milan, Italy - Author

Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy - Author

Univ Padua, Haemophilia Ctr, Med Clin 2, Padua, Italy - Author

Univ Perugia, Dept Med, Haemophilia Ctr, Azienda Osped Perugia, Perugia, Italy - Author

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 (R)/Alphanate (R) (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<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.

Keywords

Clinical-efficacyCohortDesmopressinDiagnosisFactor viiiFactor-viiiFanhdi(r)ManagementOn-demand treatmentReplacement therapySafetySecondary long-term prophylaxisVon willebrand diseaseVon willebrand factor

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Blood Transfusion due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine (Miscellaneous).

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.82. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

Weighted Average of Normalized Impact by the Scopus agency: 2.18 (source consulted: FECYT Feb 2024)
Field Citation Ratio (FCR) from Dimensions: 18.19 (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-11, the following number of citations:

WoS: 34
Scopus: 46
Europe PMC: 16
OpenCitations: 22

Impact and social visibility

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Canada; Germany; Italy.

Indexed in

License and use

Citations

Altmetrics

Grant support

Analysis of institutional authors

Share