Rationale and study design of a randomized controlled trial to investigate the effect of romosozumab on bone mineral density in hemodialysis patients with osteoporosis (the TRINITY study): A study protocol

Abstract Background Dialysis patients are at a high risk of fracture; however, little evidence is currently available regarding optimal treatment strategies. Romosozumab is a new drug for osteoporosis that promotes bone formation and inhibits bone resorption. This controlled study aims to clarify the effect of romosozumab on bone mineral density and fractures in patients undergoing hemodialysis who have developed osteoporosis. Methods The TRINITY study is a 12-month multicenter, open-label, randomized (1:1), parallel-group trial in patients undergoing maintenance hemodialysis with osteoporosis. A total of 100 patients are to be randomly allocated to receive romosozumab 210 mg once a month via subcutaneous injection or to the control (standard therapy) group. The primary endpoint of this trial is the percentage change in bone mineral density (BMD) at the lumbar vertebrae with dual-energy X-ray absorptiometry (DXA) after 12 months of treatment relative to the baseline between the romosozumab intervention and control groups. The proportion of patients without new fracture in 2 years is also an endpoint. Results The background, rationale, and design of this trial are presented. To date, all patients have been enrolled in this trial. The study is expected to end by 2026. Conclusions The TRINITY study will demonstrate the effectiveness of romosozumab on bone mineral density and its safety, and will define a new strategy for protecting against fractures in dialysis patients with osteoporosis. Registry: Japan Registry of Clinical Trials (jRCT ) no. jRCT1041200081; registration date: 24 December 2020