Antithrombin alfa in hereditary antithrombin deficient patients: A phase 3 study of prophylactic intravenous administration in high risk situations
Andreas Tiede 1, R. Campbell Tait 2, Don W. Shaffer 3, Francesco Baudo 4, Bernard Boneu 5, Carl Erik Dempfle 6, Marie Helene Horellou 7, Robert Klamroth 8, John Lazarchick 9, Andrew D. Mumford 10, Sam Schulman 1 1, Caroline Shiach 1 2, Laura J. Bonfiglio 1 3, Johan T. M. Frieling 1 3, Jacqueline Conard 7, Mario von Depka1
1 Hannover Medical School, Hannover, Germany; 2 Royal Infirmary, Glasgow, UK; 3 WellStar Health Systems, Marietta, Georgia, USA; 4 Azienda Ospedaliera Niguarda Ca' Granda, Milan, Italy; 5 Hôpital de Rangueil, Toulouse, France; 6 Universitätsklinikum Mannheim GmbH, Mannheim, Germany; 7 Hôpital de l' Hôtel Dieu, Paris, France; 8 Vivantes Klinikum im Friedrichshain, Berlin, Germany; 9 Medical University of South Carolina, Charleston, South Carolina, USA; 10 Bristol Haematology and Oncology Centre, Bristol, UK; 11 Karolinska University Hospital, Stockholm, Sweden; 12 Manchester Royal Infirmary, Manchester, UK; 13 GTC Biotherapeutics, Framingham, Massachusetts, USA
Deep vein thrombosis, Hereditary antithrombin deficiency, recombinant human antithrombin, antithrombin alfa, ATryn®
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 hereditaryAT 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.