Phase 3 trials of new anticoagulants for thromboprophylaxis
. | . | . | . | . | . | . | Main results . | . | |
|---|---|---|---|---|---|---|---|---|---|
| Anticoagulant . | Study . | No. of patients . | Population . | Regimen . | Control . | Outcome measure . | Outcome measure . | Major bleeding . | |
| Fondaparinux | EPHESUS25 | 2309 | THR | 2.5 mg SC OD postoperatively | Enoxaparin 40 mg OD preoperatively | Venographically detected DVT and symptomatic VTE to d 11 | Fond: 37/908 (4.1%) | Fond: 47/1140 (4.1%) | |
| Enox: 85/919 (9.2%) | Enox: 32/1133 (2.8%) | ||||||||
| P < .0001 | NS | ||||||||
| PENTATHLON-200026 | 2275 | THR | 2.5 mg SC OD, postoperatively | Enoxaparin 30 mg bid postoperatively | Fond: 48/787 (6.1%) | Fond: 20/1128 (1.7%) | |||
| Enox: 66/797 (8.3%) | Enox: 11/1129 (0.9%) | ||||||||
| NS | NS | ||||||||
| PENTAMAKS27 | 1049 | TKR | 2.5 mg SC OD postoperatively | Enoxaparin 30 mg bid postoperatively | Fond: 45/361 (12.5%) | Fond: 10/517 (1.9%) | |||
| Enox: 101/363 (27.8%) | Enox: 1/517 (0.2%) | ||||||||
| P < .001 | P = .006 | ||||||||
| PENTHIFRA28 | 1711 | Hip fracture | 2.5 mg SC OD postoperatively | Enoxaparin 40 mg OD preoperatively | Fond: 52/626 (8.3%) | Fond: 11/831 (1.3%) | |||
| Enox: 119/624 (19.1%) | Enox: 19/842 (2.3%) | ||||||||
| P < .001 | NS | ||||||||
| PENTHIFRA-Plus29 | 656 | Hip fracture | 2.5 mg SC OD × 3 wk after initial 7 d of fondaparinux | Placebo after initial 7 d of fondaparinux | Venographically detected DVT and symptomatic VTE at 3 wk | Fond: 3/208 (1.4%) | Fond: 8/327 (2.4%) | ||
| Placebo: 77/220 (35%) | Placebo: 2/329 (0.6%) | ||||||||
| P < .001 | NS | ||||||||
| PEGASUS30 | 2927 | General surgery | 2.5 mg SC OD × 5-9 d postoperatively | Dalteparin 2500 IU preoperatively and 1st dose postoperatively, then 5000 IU × 5-9 d | Venographically detected DVT and symptomatic VTE to d 10 | Fond: 4.6%* | Fond: 3.4%* | ||
| Dalteparin: 6.1% | Dalteparin: 2.4% | ||||||||
| NI | NS | ||||||||
| ARTEMIS31 | 849 | Medical | 2.5 mg SC OD × 6-14 d | Placebo × 6-14 d | Venographically detected DVT and symptomatic DVT and PE to d 15 | Fond: 5.6%* | Fond: 0.2%* | ||
| Placebo: 10.5% | Placebo: 0.2% | ||||||||
| P = .03 | NS | ||||||||
| Ximelagratran | METHRO-III32 | 2788 | THR/TKR | Melagatran 3 mg SC postoperatively, then ximelagatran 24 mg bid × 8-11 d | Enoxaparin 40 mg OD SC preoperatively, then × 8-11 d | Venographically detected DVT and symptomatic VTE to d 11 | Xim: 355/1146 (31%) | Xim: 20/1399 (1.7%) | |
| Enox: 306/1122 (27.3%) | Enox: 23/1389 (0.9%) | ||||||||
| NS | NS | ||||||||
| Platinum-hip33 | 1838 | THR | Ximelagatran 24 mg bid × 7-12 d postoperatively | Enoxaparin 30 mg bid SC × 7-12 d postoperatively | Venographically detected DVT and symptomatic VTE to d 12 | Xim: 62/782 (7.9%) | Xim: 7/906 (0.8%) | ||
| Enox: 36/775 (4.6%) | Enox: 8/910 (0.9%) | ||||||||
| P < .05; NNI | NS | ||||||||
| Platinum-knee34 | 680 | TKR | Ximelagatran 24 mg bid × 7-12 d postoperatively | Warfarin INR 2-3.0 × 7-12 d postoperatively | Venographically detected DVT and symptomatic VTE to d 12 | Xim: 53/276 (19.2%) | Xim: 6/345 (1.7%) | ||
| Warfarin: 67/261 (25.7%) | Warfarin: 3/330 (0.9%) | ||||||||
| NS | NS | ||||||||
| EXULT A35 | 2301 | TKR | Ximelagatran 24 mg OR 36 mg bid × 7-12 d postoperatively | Warfarin INR 2-3.0 × 7-12 d postoperatively | Total VTE and all-cause mortality to d 12 | Xim 36 mg: 128/629 (20%) | Xim 36 mg: 6/769 (0.8%) | ||
| Xim 24 mg: 153/614 (25%) | Xim 24 mg: 6/757 (0.8%) | ||||||||
| Warfarin: 168/608 (28%) | Warfarin: 5/759 (0.7%) | ||||||||
| P = .003† | NS | ||||||||
| EXPRESS36 | 2835 | THR/TKR | Melagatran 2 mg SC preoperatively, 3 mg SC postoperatively, then ximelagatran 24 mg bid × 8-11 d | Enoxaparin 40 mg OD SC × 8-11 d preoperatively | Venographically detected proximal DVT, symptomatic VTE, and death where PE could not be excluded to d 12 | Xim: 26/1138 (2.3%) | Xim: 46/1,378 (3.3%) | ||
| Enox: 74/1178 (6.3%) | Enox: 16/1387 (1.2%) | ||||||||
| p = .001 | P = NA | ||||||||
| EXULT B37 | 2303 | TKR | Ximelagatran 36 mg bid × 7-12 d postoperatively | Warfarin INR 2-3.0 × 7-12 d postoperatively | Total VTE and all-cause mortality to d 14 | Xim: 22.5%* | Xim: 1.0%* | ||
| Warfarin: 31.9% | Warfarin: 0.4% | ||||||||
| P < .001 | NS | ||||||||
. | . | . | . | . | . | . | Main results . | . | |
|---|---|---|---|---|---|---|---|---|---|
| Anticoagulant . | Study . | No. of patients . | Population . | Regimen . | Control . | Outcome measure . | Outcome measure . | Major bleeding . | |
| Fondaparinux | EPHESUS25 | 2309 | THR | 2.5 mg SC OD postoperatively | Enoxaparin 40 mg OD preoperatively | Venographically detected DVT and symptomatic VTE to d 11 | Fond: 37/908 (4.1%) | Fond: 47/1140 (4.1%) | |
| Enox: 85/919 (9.2%) | Enox: 32/1133 (2.8%) | ||||||||
| P < .0001 | NS | ||||||||
| PENTATHLON-200026 | 2275 | THR | 2.5 mg SC OD, postoperatively | Enoxaparin 30 mg bid postoperatively | Fond: 48/787 (6.1%) | Fond: 20/1128 (1.7%) | |||
| Enox: 66/797 (8.3%) | Enox: 11/1129 (0.9%) | ||||||||
| NS | NS | ||||||||
| PENTAMAKS27 | 1049 | TKR | 2.5 mg SC OD postoperatively | Enoxaparin 30 mg bid postoperatively | Fond: 45/361 (12.5%) | Fond: 10/517 (1.9%) | |||
| Enox: 101/363 (27.8%) | Enox: 1/517 (0.2%) | ||||||||
| P < .001 | P = .006 | ||||||||
| PENTHIFRA28 | 1711 | Hip fracture | 2.5 mg SC OD postoperatively | Enoxaparin 40 mg OD preoperatively | Fond: 52/626 (8.3%) | Fond: 11/831 (1.3%) | |||
| Enox: 119/624 (19.1%) | Enox: 19/842 (2.3%) | ||||||||
| P < .001 | NS | ||||||||
| PENTHIFRA-Plus29 | 656 | Hip fracture | 2.5 mg SC OD × 3 wk after initial 7 d of fondaparinux | Placebo after initial 7 d of fondaparinux | Venographically detected DVT and symptomatic VTE at 3 wk | Fond: 3/208 (1.4%) | Fond: 8/327 (2.4%) | ||
| Placebo: 77/220 (35%) | Placebo: 2/329 (0.6%) | ||||||||
| P < .001 | NS | ||||||||
| PEGASUS30 | 2927 | General surgery | 2.5 mg SC OD × 5-9 d postoperatively | Dalteparin 2500 IU preoperatively and 1st dose postoperatively, then 5000 IU × 5-9 d | Venographically detected DVT and symptomatic VTE to d 10 | Fond: 4.6%* | Fond: 3.4%* | ||
| Dalteparin: 6.1% | Dalteparin: 2.4% | ||||||||
| NI | NS | ||||||||
| ARTEMIS31 | 849 | Medical | 2.5 mg SC OD × 6-14 d | Placebo × 6-14 d | Venographically detected DVT and symptomatic DVT and PE to d 15 | Fond: 5.6%* | Fond: 0.2%* | ||
| Placebo: 10.5% | Placebo: 0.2% | ||||||||
| P = .03 | NS | ||||||||
| Ximelagratran | METHRO-III32 | 2788 | THR/TKR | Melagatran 3 mg SC postoperatively, then ximelagatran 24 mg bid × 8-11 d | Enoxaparin 40 mg OD SC preoperatively, then × 8-11 d | Venographically detected DVT and symptomatic VTE to d 11 | Xim: 355/1146 (31%) | Xim: 20/1399 (1.7%) | |
| Enox: 306/1122 (27.3%) | Enox: 23/1389 (0.9%) | ||||||||
| NS | NS | ||||||||
| Platinum-hip33 | 1838 | THR | Ximelagatran 24 mg bid × 7-12 d postoperatively | Enoxaparin 30 mg bid SC × 7-12 d postoperatively | Venographically detected DVT and symptomatic VTE to d 12 | Xim: 62/782 (7.9%) | Xim: 7/906 (0.8%) | ||
| Enox: 36/775 (4.6%) | Enox: 8/910 (0.9%) | ||||||||
| P < .05; NNI | NS | ||||||||
| Platinum-knee34 | 680 | TKR | Ximelagatran 24 mg bid × 7-12 d postoperatively | Warfarin INR 2-3.0 × 7-12 d postoperatively | Venographically detected DVT and symptomatic VTE to d 12 | Xim: 53/276 (19.2%) | Xim: 6/345 (1.7%) | ||
| Warfarin: 67/261 (25.7%) | Warfarin: 3/330 (0.9%) | ||||||||
| NS | NS | ||||||||
| EXULT A35 | 2301 | TKR | Ximelagatran 24 mg OR 36 mg bid × 7-12 d postoperatively | Warfarin INR 2-3.0 × 7-12 d postoperatively | Total VTE and all-cause mortality to d 12 | Xim 36 mg: 128/629 (20%) | Xim 36 mg: 6/769 (0.8%) | ||
| Xim 24 mg: 153/614 (25%) | Xim 24 mg: 6/757 (0.8%) | ||||||||
| Warfarin: 168/608 (28%) | Warfarin: 5/759 (0.7%) | ||||||||
| P = .003† | NS | ||||||||
| EXPRESS36 | 2835 | THR/TKR | Melagatran 2 mg SC preoperatively, 3 mg SC postoperatively, then ximelagatran 24 mg bid × 8-11 d | Enoxaparin 40 mg OD SC × 8-11 d preoperatively | Venographically detected proximal DVT, symptomatic VTE, and death where PE could not be excluded to d 12 | Xim: 26/1138 (2.3%) | Xim: 46/1,378 (3.3%) | ||
| Enox: 74/1178 (6.3%) | Enox: 16/1387 (1.2%) | ||||||||
| p = .001 | P = NA | ||||||||
| EXULT B37 | 2303 | TKR | Ximelagatran 36 mg bid × 7-12 d postoperatively | Warfarin INR 2-3.0 × 7-12 d postoperatively | Total VTE and all-cause mortality to d 14 | Xim: 22.5%* | Xim: 1.0%* | ||
| Warfarin: 31.9% | Warfarin: 0.4% | ||||||||
| P < .001 | NS | ||||||||
THR indicates total hip replacement; SC, subcutaneously; OD, once daily; bid, twice daily; TKR, total knee replacement; NI, noninferiority criteria were met; NNI, noninferiority criteria were not met; NA, not available.
Results published in abstract only, raw data unavailable.
P value refers to comparison between ximelagatran 36 mg/d and warfarin.