Single 270 μg kg-1-dose rFVIIa vs. standard 90 μg kg-1-dose rFVIIa and APCC for home treatment of joint bleeds in haemophilia patients with inhibitors:: a randomized comparison

被引:131
作者
Young, G. [1 ]
Shafer, F. E. [2 ]
Rojas, P. [3 ]
Seremetis, S. [4 ]
机构
[1] Childrens Hosp Orange Cty, Orange, CA 92668 USA
[2] St Christophers Hosp Children, Philadelphia, PA 19133 USA
[3] Novo Nordisk Inc, Princeton, NJ USA
[4] Novo Nordisk AS, DK-2880 Bagsvaerd, Denmark
关键词
bleeding disorder; FEIBA; haemophilia; NovoSeven; recombinant FVIIa;
D O I
10.1111/j.1365-2516.2007.01601.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Evidence suggests greater doses of recombinant activated factor VII (rFVIIa; NovoSeven((R)), Novo Nordisk A/S, Bagsv similar to rd, Denmark) than currently administered may result in enhanced haemostasis and convenience for patients with haemophilia A and B with inhibitors. This study evaluated efficacy and safety of rFVIIa and an activated prothrombin complex concentrate (APCC; Factor Eight Inhibitor Bypassing Activity [FEIBA]((R)), Baxter AG, Vienna, Austria) for controlling joint bleeds in a home-treatment setting. Patients received each of three treatments in one of six possible sequences: 270 mu g kg(-1) rFVIIa at hour 0 + placebo at hours 3 and 6, 90 mu g kg(-1) rFVIIa at hours 0, 3 and 6, and 75 U kg(-1) APCC at hour 0. Efficacy was assessed by the requirement for additional haemostatics within 9 h and by a novel global response algorithm. The percentage of rFVIIa 270 mu g kg(-1) group patients requiring additional haemostatics within 9 h (8.3%) was significantly lower than that for the APCC group (36.4%, P = 0.032). The percentage of rFVIIa 90 x 3 mu g kg(-1) group patients requiring such rescue medication (9.1%) was also lower compared to the APCC group. This result approached, but did not reach statistical significance (P = 0.069). Both rFVIIa treatment groups showed similar use of rescue medication (8.3% and 9.1% of episodes for rFVIIa 270 mu g kg(-1) and rFVIIa 90 x 3 mu g kg(-1) groups respectively). No significant differences in treatment response were observed with the global response algorithm (P = 0.173). No safety issues were identified. A single dose of rFVIIa 270 mu g kg(-1) is as safe and effective as rFVIIa 90 x 3 mu g kg(-1) dosing, and may be considered a potentially more effective alternative to APCCs for the management of joint bleeding in this population.
引用
收藏
页码:287 / 294
页数:8
相关论文
共 18 条
[1]   Dose optimization of recombinant factor VIIa for control of mild to moderate bleeds in inhibitor patients: Improved efficacy with higher dosing [J].
Abshire, TC .
SEMINARS IN HEMATOLOGY, 2004, 41 (01) :3-7
[2]  
Al-Trabolsi H, 1998, BLOOD, V92, p104B
[3]   Manipulation of prothrombin concentration improves response to high-dose factor VIIa in a cell-based model of haemophilia [J].
Allen, Geoffrey A. ;
Hoffman, Maureane ;
Roberts, Harold R. ;
Monroe, Dougald M. .
BRITISH JOURNAL OF HAEMATOLOGY, 2006, 134 (03) :314-319
[4]   A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study [J].
Astermark, Jan ;
Donfield, Sharyne M. ;
DiMichele, Donna M. ;
Gringeri, Alessandro ;
Gilbert, Steven A. ;
Waters, Jennifer ;
Berntorp, Erik .
BLOOD, 2007, 109 (02) :546-551
[5]   Mechanism of factor VIIa-dependent coagulation in hemophilia blood [J].
Butenas, S ;
Brummel, KE ;
Branda, RF ;
Paradis, SG ;
Mann, KG .
BLOOD, 2002, 99 (03) :923-930
[6]   The effect of recombinant factor VIIa (NovoSeven™) in healthy volunteers receiving acenocoumarol to an International Normalized Ratio above 2.0 [J].
Erhardtsen, E ;
Nony, P ;
Dechavanne, M ;
Ffrench, P ;
Boissel, JP ;
Hedner, U .
BLOOD COAGULATION & FIBRINOLYSIS, 1998, 9 (08) :741-748
[7]  
Glazer S, 1995, ADV EXP MED BIOL, V386, P163
[8]   Cutaneous wound healing is impaired in hemophilia B [J].
Hoffman, Maureane ;
Harger, Anna ;
Lenkowski, Angela ;
Hedner, Ulla ;
Roberts, Harold R. ;
Monroe, Dougald M. .
BLOOD, 2006, 108 (09) :3053-3060
[9]   Home treatment of haemarthroses using a single dose regimen of recombinant activated factorVII in patients with haemophilia and inhibitors - A multi-centre, randomised, double-blind, cross-over trial [J].
Kavakli, K ;
Makris, M ;
Zulfikar, B ;
Erhardtsen, E ;
Abrams, ZS ;
Kenet, G .
THROMBOSIS AND HAEMOSTASIS, 2006, 95 (04) :600-605
[10]   A new approach to treatment of bleeding episodes in young hemophilia patients:: a single bolus megadose of recombinant activated factor VII (NovoSeven®) [J].
Kenet, G ;
Lubetsky, A ;
Luboshitz, J ;
Martinowitz, U .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2003, 1 (03) :450-455