2019
Desmopressin treatment combined with clotting factor VIII concentrates in patients with non-severe haemophilia A: protocol for a multicentre single-armed trial, the DAVID study
Publication
Publication
BMJ Open , Volume 9 - Issue 4
Abstract
Introduction
Haemophilia A is an inherited bleeding disorder
characterised by factor VIII (FVIII) deficiency. In patients with
non-severe haemophilia A, surgery and bleeding are the
main indications for treatment with FVIII concentrate. A recent
study reported that standard dosing frequently results in FVIII
levels (FVIII:C) below or above FVIII target ranges, leading to
respectively a bleeding risk or excessive costs. In addition,
FVIII concentrate treatment carries a risk of development of
neutralising antibodies. An alternative is desmopressin, which
releases endogenous FVIII and von Willebrand factor. In most
patients with non-severe haemophilia A, desmopressin alone
is not enough to achieve FVIII target levels during surgery or
bleeding. We hypothesise that combined pharmacokinetic
(PK)-guided administration of desmopressin and FVIII
concentrate may improve dosing accuracy and reduces FVIII
concentrate consumption.
Methods and analysis
In the DAVID study, 50 patients
with non-severe haemophilia A (FVIII:C ≥0.01IU/mL) with
a bleeding episode or undergoing surgery will receive
desmopressin and FVIII concentrate combination treatment.
The necessary dose of FVIII concentrate to reach FVIII target
levels after desmopressin administration will be calculated
with a population PK model. The primary endpoint is the
proportion of patients reaching FVIII target levels during the
first 72hours after start of the combination treatment. This
approach was successfully tested in one pilot patient who
received perioperative combination treatment.
Ethics and dissemination
The DAVID study was
approved by the medical ethics committee of the
Erasmus MC. Results of the study will be communicated
trough publication in international scientific journals and
presentation at (inter)national conferences.
Trial registration number NTR5383; Pre-results
Additional Metadata | |
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doi.org/10.1136/bmjopen-2018-022719, hdl.handle.net/1765/117698 | |
BMJ Open | |
Organisation | Department of Pediatrics |
Schutte, L.M., Cnossen, M., van Hest, R., Driessens, MHE, Fijnvandraat, K., Polinder, S., … Kruip, M. (2019). Desmopressin treatment combined with clotting factor VIII concentrates in patients with non-severe haemophilia A: protocol for a multicentre single-armed trial, the DAVID study. BMJ Open, 9(4). doi:10.1136/bmjopen-2018-022719 |