StrAtegies For Zoledronic Acid Post-dEnosumab Discontinuation in Postmenopausal oSTeoporosis
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 17
- 主要终点
- Maintain lumbar bone mineral density (BMD) after 1 year of ZOL
研究概览
简要总结
Denosumab (Dmab) is a treatment for postmenopausal osteoporosis. However, its withdrawal is associated with a rebound phenomenon associated with an unexpected increased risk of vertebral fractures. Defining the optimal strategy for Dmab withdrawal is critically needed. Investigator propose an open-label randomized superiority strategy trial to compare the 1-year lumbar densitometric efficacy of biomarkers-driven zoledronate (ZOL) infusion vs standardized ZOL treatment to mitigate rebound phenomenon.
详细描述
Denosumab (Dmab) is a potent and validated treatment for postmenopausal osteoporosis. However, its withdrawal, especially after reaching therapeutic target, is associated with a rebound phenomenon characterized by: (i) an increase in bone turnover markers levels usually within first 6 months off-treatment, (ii) a decrease in BMD, and (iii) an unexpected increased risk of (multiple) vertebral fractures. Although current experts' recommendations propose a post-Dmab bisphosphonates therapy (such as ZOL) to mitigate rebound phenomenon, the optimal strategy is still matter of debate. Data suggesting a protective effect with bisphosphonates (1 infusion of ZOL or weekly alendronate) are scarce, with discrepancies, and highlight that a substantial proportion of patients experiences rebound-related bone loss despite bisphosphonate therapy. Crosslaps, a bone turnover maker, are available for daily clinical practice and reflect the antiresorptive activity of anti-resorptive drugs such as bisphosphonates. Investigator hypothesize that monitoring crosslaps levels, can help to identify patients requiring more intensive bisphosphonate (additional ZOL infusion) therapy to control the post-Dmab rebound phenomenon.
Investigator propose to compare 2 strategies for Dmab withdrawal in postmenopausal osteoporosis: a standard treatment control group treated with a single ZOL infusion versus a biomarker-guided ZOL group with an additional ZOL infusion in case of insufficient inhibition of bone resorption according to crosslaps.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women with post-menopausal osteoporosis
- •And treated with denosumab for at least 2 years and reaching decision of denosumab withdrawal because of achieved therapeutic target defined as no fracture during treatment; no new risk factors; no BMD decrease > 0.03 g/cm² at the spine or hip;
- •And with a history of severe fracture or a femoral or lumbar T-score ≤ -2.5 prior denosumab initiation.
排除标准
- •Dmab use for bone disease other than post-menopausal osteoporosis.
- •Uncontrolled endocrine diseases. Liver failure.
- •Use of medication affecting bone metabolism during the last year, including bisphosphonates, teriparatide, romosozumab, Selective Estrogen Receptor Modulators, breast cancer hormonotherapy, glucocorticoids over 5 mg/day.
- •Contra-indication to bisphosphonates according to license recommendation including chronic kidney disease with GFR stage > or = G3b. Prior intolerance to zoledronic acid.
- •Subjects unable to give an informed consent or to fill the case report form. Subjects under law protection.
- •Foreseeable poor compliance with the strategy, alcoholism, toxicomania.
研究组 & 干预措施
Intensive biomarkers-guided arm
A second infusion when crosslaps levels reach 300 pg/mL, no later than month-12
干预措施: a second infusion of ZOL when crosslaps levels reach 300 pg/mL (Drug)
Standard treatment arm
Potentially a rescue second infusion at month-12, in case unfavourable outcome (incident osteoporotic fractures) or high risk of unfavourable outcome
干预措施: a rescue second infusion at month-12 (standard traitment) (Drug)
结局指标
主要结局
Maintain lumbar bone mineral density (BMD) after 1 year of ZOL
时间窗: 1 year after inclusion
The proportion of patients who failed to maintain lumbar BMD after 1 year of ZOL according to the Least Significant Change (LSC) criterion
次要结局
- Maintain hip bone mineral density (BMD) after 1 year of ZOL(1 year after inclusion)
- the changes in hip and lumbar BMD from baseline(Day 0, 1 year after inclusion, 2 year after inclusion)
- the changes from baseline in bone turnover markers(1 year after inclusion, 2 year after inclusion)
- morphometric vertebral fractures(1 year after inclusion, 2 year after inclusion)
- Patients requiring a second ZOL(1 year after inclusion, 2 year after inclusion)
- Relation between biomarker values and densitometry evolution(3, 6, 9, 12 months after inclusion)
- Relation between biomarker values and appearance of new vertebral fracture(3, 6, 9, 12 months after inclusion)