Denosumab Treatment in Patients With Chronic Kidney Disease (CKD) at High Risk of Fracture: A Prospective, Randomised Controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 102
- 试验地点
- 1
- 主要终点
- Rate of bone mineral density (BMD) decline at the lumbar spine
研究概览
简要总结
Objective: To verify the efficacy and safety of denosumab in the prevention and treatment of CKD-MBD in CKD patients with high risk of fracture.
Methods: A cohort of CKD patients with high risk of fracture was established and followed up for long periods (≥24 months). Patients with CKD3b-5D stage and fracture risk assessment tool (FRAX) scores at high risk or very high risk of fracture were enrolled. A multicenter, prospective, open-label, randomised controlled, interventional study was conducted. The patients were divided into two groups. The patients in the denosumab group received subcutaneous injection of denosumab 60mg once every 6 months, and the patients in the non-denosumab group received conventional treatment. Bone metabolic markers (serum calcium, phosphorus, vitamin D, parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase 5b, osteocalcin, total N-terminal propeptide of type I collagen, etc.), bone mineral density (dual-energy X-ray, quantitative CT), and vascular calcification score were regularly monitored. All adverse events (all-cause death, cardiovascular death, cardiac events, fracture, hospitalization, emergency department visits, etc.) were recorded during the follow-up period. Bone mineral density and clinical parameters were compared between the two groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years old;
- •Stage 3b-5D chronic kidney disease;
- •The 10-year probability of hip fracture assessed by fracture risk assessment tool (FRAX) was >5%;
- •Voluntarily signed informed consent.
排除标准
- •Age < 18 or ≥100 years;
- •Premenopausal women;
- •Denosumab was absolutely contraindicated;
- •Had received denosumab or bisphosphonates therapy;
- •Tertiary hyperparathyroidism;
- •Patients with malignant tumor;
- •Patients at risk for osteonecrosis of the jaw;
- •Estimated follow-up time ≤12 months.
研究组 & 干预措施
Denosumab group
Fifty-one patients were randomly assigned to the denosumab group, which received subcutaneous injection of denosumab 60mg once every 6 months. Serum calcium, phosphorus, alkaline phosphatase, iPTH, tPINP, 25(OH)VitD, DXA and qCT were measured before medication. Serum calcium, phosphorus and iPTH were examined at day 1, 7 and 14, alkaline phosphatase, tPINP and 25(OH)VitD at day 7 and 14, and electrocardiogram at day 1 and 7 after treatment. Intravenous calcium supplementation was required if muscle spasms and QT prolongation occurred. Six months after medication, subcutaneous injections of denosumab 60mg were repeated. The protocol was repeated every 6 months, totally 24 months. Bone mineral density, clinical parameters and adverse events were evaluated at 24 months.
干预措施: Denosumab (Drug)
Non-denosumab group
The other 51 patients did not use denosumab and used other medications, such as diphosphonates, active vitamin D and/or active vitamin D analogue, calcimimetics, calcitonin, estrogen receptor agonists, etc. At the same time, calcium and vitamin D were supplemented. The baseline serum calcium, phosphorus, alkaline phosphatase, iPTH, tPINP, 25(OH)VitD, DXA, and qCT were measured. The above parameters were rechecked every 6 months, and the medications was recorded, totally 24 months.
干预措施: Non-denosumab (Drug)
结局指标
主要结局
Rate of bone mineral density (BMD) decline at the lumbar spine
时间窗: 24 months
Rate of BMD decline =\[(BMD24-BMD Baseline)÷BMD baseline\]\*100%
次要结局
- Rate of fresh fractures, cardiovascular cerebrovascular adverse events and all-cause mortality(24 months)
研究者
Dongliang Zhang, MD
Director of Nephrology Department of Beijing Jishuitan Hospital
Capital Medical University