PMID- 30747707
OWN - NLM
STAT- MEDLINE
DCOM- 20200302
LR  - 20200302
IS  - 2385-2070 (Electronic)
IS  - 1723-2007 (Print)
IS  - 1723-2007 (Linking)
VI  - 17
IP  - 5
DP  - 2019 Sep
TI  - A phase III study comparing secondary long-term prophylaxis versus on-demand 
      treatment with vWF/FVIII concentrates in severe inherited von Willebrand disease.
PG  - 391-398
LID - 10.2450/2019.0183-18 [doi]
AB  - 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<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.
FAU - Peyvandi, Flora
AU  - Peyvandi F
AD  - Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi 
      Haemophilia and Thrombosis Centre, Milan, Italy.
AD  - Department of Pathophysiology and Transplantation, University of Milan, Milan, 
      Italy.
FAU - Castaman, Giancarlo
AU  - Castaman G
AD  - Haemophilia and Thrombosis Center, "San Bortolo" Hospital, Vicenza, Italy.
AD  - Centre for Bleeding Disorders and Coagulation, "Careggi" University Hospital, 
      Florence, Italy.
FAU - Gresele, Paolo
AU  - Gresele P
AD  - Department of Medicine, University of Perugia, Haemophilia Center, Azienda 
      Ospedaliera di Perugia, Perugia, Italy.
FAU - De Cristofaro, Raimondo
AU  - De Cristofaro R
AD  - Haemorrhagic and Thrombotic Diseases Unit, "A. Gemelli" University Hospital 
      Foundation IRCCS, Institute of Internal Medicine and Geriatrics, Catholic 
      University "S. Cuore", Rome, Italy.
FAU - Schinco, Piercarla
AU  - Schinco P
AD  - Regional Reference Center for Hereditary Haemorrhagic and Thrombotic Diseases of 
      Adult Patients, "Le Molinette" Hospital, Turin Italy.
FAU - Bertomoro, Antonella
AU  - Bertomoro A
AD  - Haemophilia Centre, II Clinica Medica, University of Padua, Padua, Italy.
FAU - Morfini, Massino
AU  - Morfini M
AD  - Italian Association of Haemophilia Centres, Milan, Italy.
FAU - Gamba, Gabriella
AU  - Gamba G
AD  - Haemophilia Centre and Congenital Coagulopathies Unit,"S. Matteo" University 
      Hospital, Pavia, Italy.
FAU - Barillari, Giovanni
AU  - Barillari G
AD  - Sos Malattie Emorragiche e Trombotiche, Dipartimento di Area Vasta di Medicina 
      Trasfusionale, Presidio Ospedaliero "S. Maria della Misericordia", ASUI di Udine, 
      Udine, Italy.
FAU - Jimenez-Yuste, Victor
AU  - Jimenez-Yuste V
AD  - Haematology Department, "La Paz" University Hospital, "Autonoma" University, 
      Madrid, Spain.
FAU - Konigs, Cristoph
AU  - Konigs C
AD  - University Hospital Frankfurt, "Goethe" University, Department of Pediatrics, 
      Frankfurt am Main, Germany.
FAU - Iorio, Alfonso
AU  - Iorio A
AD  - Department of Health Research Methods, Evidence, and Impact and Department of 
      Medicine, McMaster University, Hamilton, Canada.
AD  - Department of Medicine, University of Perugia, Haemophilia Center, Azienda 
      Ospedaliera di Perugia, Perugia, Italy.
FAU - Federici, Augusto B
AU  - Federici AB
AD  - Division of Haematology and Transfusion Medicine, "Luigi Sacco" University 
      Hospital, Milan, Italy.
AD  - Department of Oncology and Onco-Haematology, University of Milan, Milan, Italy.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20190204
PL  - Italy
TA  - Blood Transfus
JT  - Blood transfusion = Trasfusione del sangue
JID - 101237479
RN  - 0 (Drug Combinations)
RN  - 0 (factor VIII, von Willebrand factor drug combination)
RN  - 0 (von Willebrand Factor)
RN  - 9001-27-8 (Factor VIII)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Drug Combinations
MH  - Factor VIII/administration & dosage/adverse effects/*therapeutic use
MH  - Female
MH  - Hemorrhage/drug therapy/etiology/*prevention & control
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
MH  - Young Adult
MH  - von Willebrand Diseases/complications/*drug therapy/prevention & control
MH  - von Willebrand Factor/administration & dosage/adverse effects/*therapeutic use
PMC - PMC6774924
COIS- Disclosure of conflicts of interest FP received honoraria or consultation fees 
      from Kedrion Biopharma and LFBa, and speaker's fees for participating at 
      educational meetings organised by Ablynx Alnylam, Grifols, Sobi, F. Hoffmann-La 
      Roche, and Shire. Member of Ablynx, F. Hoffmann-La Roche Advisory Board, and 
      Shire. GC received research funding (directly to the Institution from Pfizer, CSL 
      Behring). Member of an Entity's Board of Directors, Speakers Bureau, or its 
      Advisory Committee (CSL Behring, Shire, Bayer, Sobi, Novo Nordisk, Kedrion, 
      Genzyme, Pfizer, Roche, and Uniqure). RDC received consultation fees from Grifols 
      and Pfizer, and a speaker's fee for participating at educational meetings 
      organised by Shire. Member of Bayer Advisory Board. VJ-Y received a reimbursement 
      for attending symposia/congresses and/or honoraria for speaking and/or honoraria 
      for consulting, and/or funds for research from Shire, Bayer, CSL-Behring, 
      Grifols, Novo Nordisk, Sobi, Octapharma, and Pfizer. CK received an honoraria for 
      speaking or consulting from Bayer, Biotest, CSL Behring, Grifols, Pfizer, Roche, 
      Shire and Sobi and institutional research funding from Bayer, Biotest, Intersero, 
      Pfizer, Shire, and Sobi. AI received institutional research funding from Bayer, 
      Bioverativ, CSL, Grifols, Novo Nordisk, Octapharma, and Pfizer. ABF is involved 
      in the advisory boards of Baxalta-Shire, CSL-Behring, Grifols, Kedrion, LFB, and 
      Octapharma with honoraria related to vWD. The other Authors declare no conflicts 
      of interest.
EDAT- 2019/02/13 06:00
MHDA- 2020/03/03 06:00
PMCR- 2019/09/01
CRDT- 2019/02/13 06:00
PHST- 2018/09/18 00:00 [received]
PHST- 2019/12/19 00:00 [accepted]
PHST- 2019/02/13 06:00 [pubmed]
PHST- 2020/03/03 06:00 [medline]
PHST- 2019/02/13 06:00 [entrez]
PHST- 2019/09/01 00:00 [pmc-release]
AID - 2019.0183-18 [pii]
AID - blt-17-391 [pii]
AID - 10.2450/2019.0183-18 [doi]
PST - ppublish
SO  - Blood Transfus. 2019 Sep;17(5):391-398. doi: 10.2450/2019.0183-18. Epub 2019 Feb 
      4.