In an open-label randomized study, FRAGMIN 5,000 units administered once daily subcutaneously was compared with warfarin sodium, administered orally, in patients undergoing hip replacement surgery. Treatment with FRAGMIN was initiated with a 2,500 units dose subcutaneously within 2 hours before surgery, followed by a 2,500 units dose subcutaneously the evening of the day of surgery. Then, a dosing regimen of FRAGMIN 5,000 units subcutaneously once daily was initiated on the first postoperative day. The first dose of warfarin sodium was given the evening before surgery, then continued daily at a dose adjusted for INR 2 to 3. Treatment in both groups was then continued for 5 days to 9 days postoperatively. Of the 580 patients enrolled, 553 were treated and 550 underwent surgery. Of those who underwent surgery, 271 received FRAGMIN and 279 received warfarin sodium. The mean age of the study population was 63 years (range 20 years to 92 years) and the majority of patients were white (91.1%) and female (52.9%). The incidence of deep vein thrombosis (DVT), as determined by evaluable venography, was significantly lower for the group treated with FRAGMIN compared with patients treated with warfarin sodium (see Table 14).

In a second single-center, double-blind study of patients undergoing hip replacement surgery, FRAGMIN 5,000 units once daily subcutaneously starting the evening before surgery, was compared with heparin 5,000 units subcutaneously three times a day, starting the morning of surgery. Treatment in both groups was continued for up to 9 days postoperatively. Of the 140 patients enrolled, 139 were treated and 136 underwent surgery. Of those who underwent surgery, 67 received FRAGMIN and 69 received heparin. The mean age of the study population was 69 years (range 42 years to 87 years) and the majority of patients were female (58.8%). In the intent-to-treat analysis, the incidence of proximal DVT was significantly lower for patients treated with FRAGMIN compared with patients treated with heparin (6/67 vs 18/69; p = 0.012). The incidence of pulmonary embolism detected by lung scan was also significantly lower in the group treated with FRAGMIN (9/67 vs 19/69; p = 0.032).

A third multi-center, double-blind, randomized study evaluated a postoperative dosing regimen of FRAGMIN for thromboprophylaxis following total hip replacement surgery. Patients received either FRAGMIN or warfarin sodium, randomized into one of three treatment groups. One group of patients received the first dose of FRAGMIN 2,500 units subcutaneous within 2 hours before surgery, followed by another dose of FRAGMIN 2,500 units subcutaneous at least 4 hours (6.6 ± 2.3 hours) after surgery. Another group received the first dose of FRAGMIN 2,500 units subcutaneous at least 4 hours (6.6 ± 2.4 hours) after surgery. Then, both of these groups began a dosing regimen of FRAGMIN 5,000 units once daily subcutaneous on postoperative day 1. The third group of patients received warfarin sodium the evening of the day of surgery, then continued daily at a dose adjusted to maintain INR 2 to 3. Treatment for all groups was continued for 4 days to 8 days postoperatively, after which time all patients underwent bilateral venography.

In the total enrolled study population of 1,501 patients, 1,472 patients were treated; 496 received FRAGMIN (first dose before surgery), 487 received FRAGMIN (first dose after surgery) and 489 received warfarin sodium. The mean age of the study population was 63 years (range 18 years to 91 years) and the majority of patients were white (94.4%) and female (51.8%).

Administration of the first dose of FRAGMIN after surgery was as effective in reducing the incidence of thromboembolic reactions as administration of the first dose of FRAGMIN before surgery (44/336 vs 37/338; p =0.448). Both dosing regimens of FRAGMIN were more effective than warfarin sodium in reducing the incidence of thromboembolic reactions following hip replacement surgery.