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

Schutte, L.M.; Cnossen, M.H.; Hest, R.M. van; Driessens, M.H.E.; Fijnvandraat, K.; Polinder, S.; Beckers, E.A.M.; Coppens, M.; Eikenboom, J.; Gorkom, B.A.P.L.V.; Meijer, K.; Nieuwenhuizen, L.; Mauser-Bunschoten, E.P.; Leebeek, F.W.G.; Mathot, R.A.A.; Kruip, M.J.H.A.

doi:doi:10.1136/bmjopen-2018-022719

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...Show moreIntroduction 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 >= 0.01 IU/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 72 hours 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.Show less

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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