Document Detail

Safety, pharmacokinetics and efficacy of factor VIIa formulated with PEGylated liposomes in haemophilia A patients with inhibitors to factor VIII--an open label, exploratory, cross-over, phase I/II study.
MedLine Citation:
PMID:  20491957     Owner:  NLM     Status:  In-Process    
  Recombinant activated factor VIIa (FVIIa) is a bypassing agent used to treat bleeding episodes in haemophilia patients with inhibitors to factor VIII (FVIII) and factor IX. The pharmacological effect of FVIIa is short-lived and therefore with the recommended dose of 90 μg kg(-1), a bleeding episode is treated with multiple injections. A long-acting form of FVIIa that can ensure adequate haemostasis with a single infusion, without increasing the thrombotic risk, would therefore be beneficial. PEGylated liposomes (PEGLip) have been shown to bind FVIIa and to improve haemostatic efficacy in preclinical experiments. In the present phase I/II clinical trial, we assessed the safety and efficacy of PEGLip-formulated FVIIa in severe haemophilia A patients (FVIII≤1%) with inhibitors to FVIII. Each patient received one prophylactic infusion of standard FVIIa and one prophylactic infusion of PEGLip-formulated FVIIa. The order of the infusions was randomized and the two infusions were separated by a ten-day washout period. Efficacy assessed by thromboelastography revealed that PEGLip-FVIIa induced significantly shorter clotting times and produced higher clot firmnesses than standard FVIIa. Thrombin generation assays showed that PEGLip-FVIIa induced faster thrombin generation and higher peak levels of thrombin than standard FVIIa. These effects lasted up to 5 h postinfusion. Measurements of D-dimer, prothrombin fragment 1+2 and fibrinogen showed no significant differences between the PEGLip-FVIIa and standard FVIIa treatments. PEGLip-FVIIa therefore showed improved haemostatic efficacy without increased risk of thrombosis and may be further developed for the treatment for bleeding episodes in haemophilia patients with inhibitors.
J Spira; O Plyushch; N Zozulya; R Yatuv; I Dayan; A Bleicher; M Robinson; M Baru
Related Documents :
19181397 - Post-operative bleeding is less after partial intracapsular tonsillectomy than bipolar ...
15746637 - Recombinant factor viia use in cardiac surgery--expanding the arsenal therapy for intra...
17468547 - Usefulness of the comprehensive geriatric assessment in older patients with upper gastr...
2693077 - Is the forrest classification a useful tool for planning endoscopic therapy of bleeding...
23218627 - Intermittent pneumatic compression for venous thromboembolism prophylaxis in total knee...
24466467 - Maintenance of the therapeutic effect of two high-dosage antimuscarinics in the managem...
Publication Detail:
Type:  Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Haemophilia : the official journal of the World Federation of Hemophilia     Volume:  16     ISSN:  1365-2516     ISO Abbreviation:  Haemophilia     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9442916     Medline TA:  Haemophilia     Country:  England    
Other Details:
Languages:  eng     Pagination:  910-8     Citation Subset:  IM    
Copyright Information:
© 2010 Blackwell Publishing Ltd.
Omri Laboratories Ltd., Nes Ziona, Israel.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  A novel alanine or threonine 789 to proline mutation causing type 2N von Willebrand's disease when i...
Next Document:  Molecular analysis in two Tunisian families with combined factor V and factor VIII deficiency.