ARTEMIS.
| Methods | Multi‐centre, multi‐national, randomised, double‐blind, placebo‐controlled study | |
| Participants |
Total number of participants: 849 Number of participants allocated to each group: fondaparinux group: 429; placebo group: 420 Number of participants excluded and/or lost to follow up: fondaparinux group: 4; placebo group: 6 Inclusion: Participants were acutely ill medical patients, aged ≥ 60 years and expected to require bed rest for at least 4 days at the moment of inclusion; hospitalised for congestive heart failure New York Heart Association (NYHA) class III/IV, and/or acute respiratory illness in the presence of chronic lung disease, and/or acute infectious or inflammatory disease Exclusion: Patients were excluded from study participation on the basis of their bleeding risk at the time of randomisation (e.g. active clinically significant bleeding or medical conditions associated with a bleeding risk) criteria related to contrast dyes during venography (e.g. serum creatinine > 2 mg/dL (180 µmol/L) or hypersensitivity to contrast media) or use of anticoagulant or fibrinolytic therapy within 48 hours before randomisation. |
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| Interventions |
Fondaparinux (FX): Administration of 2.5 mg FX (2.5 mg once daily as sc injection) started 2 hours after randomisation. Study treatment was to be given at least up to and including day 6 but not after day 14. Venography had to be performed within 1 day after cessation of treatment on days 6 to 15, or earlier in case of symptomatic VTE. Placebo: Placebo was started 2 hours after randomisation. Study treatment was to be given at least up to and including day 6 but not after day 14. Venography had to be performed within 1 day after cessation of treatment on days 6 to 15, or earlier in case of symptomatic VTE. |
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| Outcomes |
Primary efficacy outcome: composite of the following VTE events recorded up to day 15 or up to the first venography, whichever came first: venogram positive for DVT, symptomatic DVT, non‐fatal PE or fatal PE. Venography and all other available diagnostic tests (ultrasonography, ventilation/perfusion lung scan, pulmonary angiography or spiral computed tomography scan, autopsy report, etc) were blindly adjudicated by experts of the Central Independent Adjudication Committee (CIAC). Primary safety outcome: major bleeding during treatment and 2 days thereafter, defined as fatal bleeding, bleeding in a critical location, bleeding leading to surgical intervention or overt bleeding associated with a drop in haemoglobin (Hb) concentration ≥ 20 g/L or leading to transfusion of 2 or more units of red blood cells Efficacy and safety outcomes were adjudicated by a central independent committee (CIAC), whose members were unaware of the treatment assignment. Accumulated safety data were regularly reviewed by an independent committee. |
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| Notes | Use of adjunctive prophylaxis methods: Use of aspirin or non‐steroidal anti‐inflammatory drugs was discouraged. Graduated compression stockings and physiotherapy were allowed. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Randomisation was carried out using a predefined central randomisation list, balanced in blocks of four" Comment: probably done |
| Allocation concealment (selection bias) | Low risk | Multi‐centre, multi‐national, randomised, double‐blind, placebo‐controlled study Comment: probably done |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "Study drugs were provided in identical boxes" Comment: probably done |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "All venograms ……were blindly adjudicated by experts of the Central Independent Adjudication Committee (CIAC)" Comment: probably done |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 89.4% and 88.7% of randomised participants in the 2 study groups, respectively, finished their treatment Comment: low risk of bias; most participants finished the study |
| 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 |