ACT2545.
| Methods | Multi‐centre, randomised, open‐label, dose‐finding study | |
| Participants |
Total number of participants: 243 Number of participants allocated to each group: fondaparinux (FX) 4 mg group: 86, FX 2 mg group: 78, enoxaparin (EN) 40 mg group: 79 Number of participants excluded and/or lost to follow‐up: FX 4 mg group: 4 (1 adverse event, 1 lack of efficacy, 2 other reasons), FX 2 mg group: 3 (1 adverse event, 0 lack of efficacy, 2 other reasons), EN 40 mg group: 3 (1 adverse event, 1 lack of efficacy, 1 other reasons) Inclusion: Men and postmenopausal women aged > 40 years with body weight 50 to 100 kg inclusive who were undergoing first single non‐revision total hip replacement (subsequently amended to non‐revision total hip replacement), with no contraindication to undergo phlebography on day 8 ± 1 Exclusion: Patients were excluded from study participation on the basis of their bleeding risk at the time of randomisation (e.g. known bleeding tendency, thrombocytes < 150 × 109/L, prothrombin time < 65%, APTT/control > 1.2 or other medical conditions associated with a bleeding risk), other significant conditions (e.g. history of PE or DVT, serum creatinine > 2.3 mg% (200 µmol/L), severe hepatic disease or uncontrolled severe high blood pressure (systolic blood pressure/diastolic blood pressure > 200/120 mmHg) or use of anticoagulant or fibrinolytic therapy within 1 week before randomisation. |
|
| Interventions |
FX: Phase I: 4 mg FX once daily. Phase II: 2 mg FX once daily; FX was administered for 7 days from day 2 (first injection planned 6 hours after surgery) to day 8. EN: Phase I: 40 mg EN once daily (first control group (CG). Phase II: 40 mg EN once daily (second CG). EN was administered for 8 days, from day 1 to day 8 (first injection planned 12 hours before surgery and first postoperative injection planned 6 hours after surgery). |
|
| Outcomes |
Primary efficacy outcome: incidence of any DVT; DVT was assessed on day 8 ± 1 by phlebography Primary safety outcome: major bleeding; major bleeding was defined as a clinically overt haemorrhage (except drain < 500 mL/d) in addition to 1 of the following criteria: haemoglobin (Hb) reduction to < 8 g/dL or Hb decrease > 2 g/dL over any 48‐hour period between day 3 and day 9 inclusive, or reoperation or intracranial bleeding or retroperitoneal or withdrawal |
|
| Notes | Use of adjunctive prophylaxis methods: No adjunctive method was used in this study. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Multicentre, randomised, open‐label, dose finding study" Comment: probably done, as earlier reports from the same company clearly describe use of random sequences |
| Allocation concealment (selection bias) | Low risk | Quote: "Multicentre, randomised, open‐label, dose finding study" Comment: probably done, as most earlier multi‐centre RCT reports clearly mention that studies of the same medicine organised by the same company were centrally randomised |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Without clear description Comment: unclear |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "A central evaluation was performed blindly by two independent experts" Comment: probably done |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 95.3%, 96.2%, 96.2% of participants in the 3 study groups finished treatment. Comment: low risk of bias |
| Selective reporting (reporting bias) | Low risk | All primary efficacy and safety outcomes listed in the Methods section were reported. Comment: low risk of bias |
| Other bias | Unclear risk | Company sponsored |