Single 270 microg kg(-1)-dose rFVIIa vs. standard 90 microg kg(-1)-dose rFVIIa and APCC for home treatment of joint bleeds in haemophilia patients with inhibitors: a randomized comparison.
Evidence suggests greater doses of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk A/S, Bagsvaerd, 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], 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 microg kg(-1) rFVIIa at hour 0 + placebo at hours 3 and 6, 90 microg 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 microg 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 microg 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 microg kg(-1) and rFVIIa 90 x 3 microg 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 microg kg(-1) is as safe and effective as rFVIIa 90 x 3 microg kg(-1) dosing, and may be considered a potentially more effective alternative to APCCs for the management of joint bleeding in this population.
Young
G
G
Children's Hospital of Orange County, Orange, CA 90027, USA. gyoung@chla.usc.edu
Shafer
F E
FE
Rojas
P
P
Seremetis
S
S
D000293:Adolescent; D000328:Adult; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015942:Factor VIIa / Q000008:administration & dosage* / Q000627:therapeutic use; D006395:Hemarthrosis / Q000188:drug therapy*; D006467:Hemophilia A / Q000188:drug therapy*; D006490:Hemostatics / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012646:Self Administration; D016896:Treatment Outcome
D001779:Blood Coagulation Factors; D006490:Hemostatics; D011994:Recombinant Proteins; C103587:recombinant FVIIa; C065655:anti-inhibitor coagulant complex; D015942:Factor VIIa