LIFT study is discontinued

Editor—We informed the BMJ about the increased risk of stroke in the long term intervention on fractures with tibolone (LIFT) study.¹ Further analysis now indicates a benefit of tibolone on risk of vertebral fracture, the primary end point of the study. Thus, the LIFT study is being stopped because of a recommendation by the data safety monitoring board that the trial has reached its objectives and additional follow-up is unlikely to provide further information about other adverse events.

LIFT is a randomised clinical trial designed to determine the effect of treatment with tibolone on risk of vertebral fracture in postmenopausal women with osteoporosis. Altogether 4538 postmenopausal women with a bone mineral density T score at the total hip or spine equal or lower than -2.5 without a fracture or a T score of -2.0 with a fracture were assigned to 1.25 mg tibolone or placebo. The average age of participants was 68 (SD 5.2) years. They are followed up periodically for clinical outcomes and safety. The trial started in 2001 and the primary outcome analysis is scheduled for June 2006.

A data safety monitoring board periodically reviews the unblinded results. A steering committee, whose voting members are investigators independent of the sponsor, Organon, oversees scientific issues. The data safety monitoring board has previously notified the sponsor and steering committee of an increased risk of stroke during an average of 2.4 years of the trial with a hazard ratio of 2.591. The updated results (at 2.75 years) for stroke (ischaemic plus haemorrhagic) and vertebral fractures (based on a semi-quantitative reading of the radiographs) for tibolone and placebo groups were respectively 25 (1.11%) and 11 (0.49%) (hazard ratio 2.3 (P = 0.02)) and 44 (2.1%) and 85 (4.1%) (hazard ratio 0.5 (P = 0.0003)).

The data safety monitoring board has recommended to us that the study be discontinued and that dispensation of all study treatments to subjects be ended as soon as practicable. We have concurred and plan to publish a more detailed report.