Prophylaxis of venous thromboembolism with subcutaneous melagatran in total hip or total knee replacement: results from Phase II studies.
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.
Eriksson
Bengt I
BI
Department of Orthopaedic Surgery, Sahlgrenska University Hospital/Ostra, S-41685, Göteborg, Sweden. b.ericksson@orthop.gu.se
Ogren
Mats
M
Eriksson
Ulf G
UG
Kälebo
Peter
P
Ahnfelt
Lennart
L
Björkström
Sven
S
Sjöstedt
Ake
A
Folestad
Agnetha
A
Arfwidsson
Ann-Christin
AC
Elvander
Christine Sareyko
CS
Frison
Lars
L
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*
D001384:Azetidines; D001596:Benzylamines; D003505:Cyclodextrins; D005343:Fibrinolytic Agents; C109573:melagatran; D005998:Glycine