Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (Novoseven) in haemophiliacs with inhibitors.
OBJECTIVE
To assess the safety and efficacy of a fixed dose of recombinant activated factor VII (rFVIIa; NovoSeven) in the home setting for mild to moderately severe joint, muscle; and mucocutaneous bleeding episodes in patients with haemophilia A or B with inhibitors.


METHODS
Multicentre, open-label, single arm, phase III study of one year duration. METHODS; Patients or their caregivers administered up to three doses of rFVIIa (90 microg/kg i.v.) at 3 h intervals within 8 h of the onset of a mild to moderate bleeding episode. Once the subject considered that rFVIIa had been "effective" with regard to haemostasis (after 1-3 injections), one further (maintenance) dose of rFVIIa was administered.


RESULTS
Of 60 patients enrolled, 56 experienced at least one bleed, and 46 completed the one year study. 614 of 877 bleeds (70%) were evaluable according to protocol definitions. Haemostasis was rated as "effective" in 92% (566/614) of evaluable bleeds after a mean of 2.2 injections. For successfully treated episodes, the time from onset of bleeding until administration of the first injection was 1.1+/-2.0 h (mean+/-SD). Twenty-four hours after initial successful response, haemostasis was reported as having been maintained in 95% of cases. Efficacy was comparable for muscle, joint and target joint, and mucocutaneous bleeding episodes. In an intent-to-treat analysis of all 877 bleeding events, efficacy outcomes were equivalent to the evaluable bleeds, with an effective response in 88% of treated episodes. Treatment-related adverse events occurred in 32 (3% of all) bleeding episodes and consisted of re-bleeds/new bleeds in more than 50% (18/32) of these events. A single episode of superficial thrombophlebitis was the only thrombotic complication encountered, and there were no patient withdrawals due to adverse events. Development of FVII(a) antibodies could not be detected, and hypersensitivity reactions to rFVIIa were not reported.


CONCLUSIONS
rFVIIa is effective and well tolerated when used in the home setting to treat mild to moderate bleeding episodes in patients with haemophilia A or B with inhibitors.
Key
N S
NS
Division of Hematology, University of Minnesota Hemophilia Treatment Center, Minneapolis 55455, USA.
Aledort
L M
LM
Beardsley
D
D
Cooper
H A
HA
Davignon
G
G
Ewenstein
B M
BM
Gilchrist
G S
GS
Gill
J C
JC
Glader
B
B
Hoots
W K
WK
Kisker
C T
CT
Lusher
J M
JM
Rosenfield
C G
CG
Shapiro
A D
AD
Smith
H
H
Taft
E
E
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005164:Factor IX / Q000276:immunology*; D005169:Factor VIII / Q000276:immunology*; D015942:Factor VIIa / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006395:Hemarthrosis / Q000188:drug therapy / Q000209:etiology; D006467:Hemophilia A / Q000150:complications* / Q000276:immunology / Q000628:therapy; D002836:Hemophilia B / Q000150:complications / Q000276:immunology / Q000628:therapy; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D006490:Hemostatics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006701:Home Nursing; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D006490:Hemostatics; D007518:Isoantibodies; D011993:Recombinant Fusion Proteins; D005169:Factor VIII; D005164:Factor IX; D015942:Factor VIIa