Levine 1994.
| Methods | Multicentre, double‐blind, randomised, placebo‐controlled trial; intention‐to‐treat analysis | |
| Participants | Patients with metastatic stage IV breast carcinoma who had been receiving first‐ or second‐line chemotherapy for 4 weeks or less. Mean age: 57 years in the warfarin group and 56 years in the placebo group; metastatic disease: not reported; previous VTE: none in warfarin and 2/159 in placebo. Mean duration of follow‐up: 199 days (SD 126) for warfarin and 188 days (SD 137) for placebo | |
| Interventions | Intervention: warfarin (1 mg daily for 6 weeks and then adjusted to maintain the INR between 1.3 to 1.9) Control: placebo Study treatment began either at the start of chemotherapy or within the next 4 weeks and continued until 1 week after termination of chemotherapy. Median treatment duration: 181 days (SD 123) for warfarin and 166 (SD 139) for placebo |
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| Outcomes | Primary outcomes: VTE and arterial thrombosis; major and minor bleeding Secondary outcome: survival |
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| Notes | Funding: study supported by a grant‐in‐aid from the National Cancer Institute of Canada Disclosure of potential conflicts of interest: none disclosed, no COI forms available |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "according to a computer‐generated random arrangement." Comment: adequate method of sequence generation |
| Allocation concealment (selection bias) | Unclear risk | Comment: method of allocation concealment not reported |
| Blinding (performance bias and detection bias) All outcomes | Low risk | Quote: "neither patients nor doctors were aware of treatment allocation" and "All outcome events were reviewed by a central adjudicating committee, unaware of treatment allocation" and "placebo patients took an identical inert tablet" Comment: adequate blinding of participants, physicians, and outcome assessors |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: For effectiveness and safety, 152 out of 154 (98.7%) in the warfarin and 159 out of 161 (98.8%) in the placebo group were analysed. |
| Selective reporting (reporting bias) | Low risk | Comment: All outcomes reported in the methods section were addressed in the results. |