Antithrombin alfa in hereditary antithrombin deficient patients: A phase 3 study of prophylactic intravenous administration in high risk situations.
During surgery and childbirth, patients with hereditary antithrombin (AT) deficiency are at high risk for thrombosis, and heparin prophylaxis may not be sufficiently efficacious. In these patients, exogenous AT may be used in association with heparin. A recombinant human AT (generic name: antithrombin alfa) has been developed. This multi-center study assessed the efficacy and safety of prophylactic intravenous administration of antithrombin alfa to hereditary AT deficient patients in high risk situations, including elective surgery, childbirth, or cesarean section. Antithrombin alfa was administered prior to and during the high risk period for restoration and maintenance of AT activity at 100% of normal. Heparin, low-molecular-weight heparin, and/or vitamin K antagonists were used according to standard of care. The primary efficacy endpoint was the incidence of acute deep vein thrombosis (DVT) from baseline up to day 30 post dosing as assessed by independent central review of duplex ultrasonograms and/or venograms. Safety was assessed based on adverse events (AEs) and laboratory evaluations. Five surgical and nine obstetrical hereditary AT deficiency patients received antithrombin alfa for a mean period of seven days. No clinically overt DVT occurred. Central review of ultrasonograms identified signs of acute DVT in two out of 13 evaluable patients. No antithrombin alfa-related AEs were reported. No patient developed anti-antithrombin alfa antibodies. In conclusion, this study suggests that antithrombin alfa is a safe and effective alternative to human plasma-derived AT for treating hereditary AT deficiency patients at high risk for thromboembolic events.
Tiede
Andreas
A
Hannover Medical School, Dept. of Haematology, Haemostasis, Oncology & Stem Cell Transplantation, Germany. tiede.andreas@mh-hannover.de
Tait
R Campbell
RC
Shaffer
Don W
DW
Baudo
Francesco
F
Boneu
Bernard
B
Dempfle
Carl Erik
CE
Horellou
Marie Helene
MH
Klamroth
Robert
R
Lazarchick
John
J
Mumford
Andrew D
AD
Schulman
Sam
S
Shiach
Caroline
C
Bonfiglio
Laura J
LJ
Frieling
Johan T M
JT
Conard
Jacqueline
J
von Depka
Mario
M
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D000991:Antithrombins / Q000008:administration & dosage* / Q000009:adverse effects / Q000172:deficiency / Q000235:genetics; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects; D025861:Blood Coagulation Disorders, Inherited / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D002585:Cesarean Section / Q000009:adverse effects; D036861:Delivery, Obstetric / Q000009:adverse effects; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D016462:Mammaplasty / Q000009:adverse effects; D008875:Middle Aged; D010690:Phlebography; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D018616:Ultrasonography, Doppler, Duplex; D014481:United States; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*
D000925:Anticoagulants; D000991:Antithrombins; D011994:Recombinant Proteins; D006493:Heparin