title: Prophylaxis of venous thromboembolism with subcutaneous melagatran in total hip or total knee replacement: results from Phase II studies.
abstract: The first clinical studies evaluating the safety and efficacy of melagatran, a novel, direct thrombin inhibitor, given subcutaneously as prophylaxis for venous thromboembolism (VTE) following total hip (THR) or total knee replacement (TKR) are reported. In Study I, 66 patients received subcutaneous melagatran (1.5-6 mg bid) in a poloxamer depot formulation, and in Study II, 104 patients received subcutaneous melagatran (2-4 mg bid) in saline or as a depot formulation in cyclodextrin. Treatment was given for 8-11 days, with the first dose administered immediately before surgery. Deep vein thrombosis (DVT) was assessed using mandatory bilateral venography on the last day of treatment, and pulmonary scintigraphy was performed if required. Bleeding complications occurred in the only patient who received melagatran 6 mg, and this dose-arm was discontinued. The frequency of VTE was low (12/129=9%, 95% confidence interval [CI]: 5-16%). Eight patients (6%) had distal DVT, three (2%) had proximal DVT, and in one patient (1%) pulmonary embolism (PE) was verified. In conclusion, subcutaneous melagatran 1.5-4.5 mg bid in saline or depot formulation was well tolerated and resulted in a low frequency of VTE.
authors.affiliation: Department of Orthopaedic Surgery, Sahlgrenska University Hospital/Ostra, S-41685, Göteborg, Sweden. b.ericksson@orthop.gu.se
authors.forename: Bengt I
authors.initials: BI
authors.lastname: Eriksson
authors.forename: Mats
authors.initials: M
authors.lastname: Ogren
authors.forename: Ulf G
authors.initials: UG
authors.lastname: Eriksson
authors.forename: Peter
authors.initials: P
authors.lastname: Kälebo
authors.forename: Lennart
authors.initials: L
authors.lastname: Ahnfelt
authors.forename: Sven
authors.initials: S
authors.lastname: Björkström
authors.forename: Ake
authors.initials: A
authors.lastname: Sjöstedt
authors.forename: Agnetha
authors.initials: A
authors.lastname: Folestad
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Arfwidsson
authors.forename: Christine Sareyko
authors.initials: CS
authors.lastname: Elvander
authors.forename: Lars
authors.initials: L
authors.lastname: Frison
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D001384:Azetidines; D001596:Benzylamines; D003505:Cyclodextrins / Q000008:administration & dosage; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005998:Glycine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010690:Phlebography; D013923:Thromboembolism / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*
chemical_list: D001384:Azetidines; D001596:Benzylamines; D003505:Cyclodextrins; D005343:Fibrinolytic Agents; C109573:melagatran; D005998:Glycine