The Comparison of Ibandronate and Zoledronic Acid After Denosumab Discontinuation: A Randomized Non-inferiority Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 52
- 试验地点
- 2
- 主要终点
- Percentage change in bone mineral density (BMD)
研究概览
简要总结
This study is a prospective, multicenter, open-label, randomized non-inferiority trial comparing intravenous ibandronate and zoledronic acid as sequential therapy after denosumab discontinuation in postmenopausal women with osteoporosis. This trial primarily targets patients with short-term denosumab exposure (less than three years) and is conducted as a preliminary investigation. The findings are expected to provide foundational evidence to inform the design of future studies assessing sequential therapies following longer-term denosumab treatment.
详细描述
Osteoporosis has been recognized by the World Health Organization (WHO) as the second most prevalent global epidemic disease, following coronary heart disease. Untreated osteoporosis may lead to a vicious cycle of recurrent fractures, resulting in disability and even mortality. In clinical practice, antiresorptive agents are commonly used as first-line therapy. Denosumab is widely preferred due to its convenient administration and potent suppression of bone turnover. However, its antiresorptive effect is reversible; discontinuation of denosumab is associated with rebound increases in bone turnover markers (BTMs) and rapid bone mineral density (BMD) loss. Therefore, subsequent antiresorptive therapy is required to prevent fracture occurrence. Zoledronic acid has been shown to effectively suppress post-denosumab rebound bone turnover and is currently considered the standard sequential treatment following denosumab discontinuation.
The objective of this study is to demonstrate that ibandronate, when used as a sequential therapy after denosumab discontinuation, provides protection comparable to zoledronic acid in patients with short-term denosumab exposure (< 3 years). This study aims to generate preliminary clinical evidence to support future trials and to offer an alternative post-denosumab treatment strategy in clinical practice. Participants will receive one year of ibandronate or zoledronic acid therapy, initiated 6 months (± 1 week) after the last dose of denosumab, followed by a total of two years of follow-up. Eligible participants will be randomized in a 1:1 ratio, with an estimated sample size of 26 patients per group.
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
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Postmenopausal women aged 50 to 85 years.
- •BMD T-score ≤ -1.5 and > -3.0 at the lumbar spine or total hip.
- •Regular treatment with denosumab administered every 6 months for at least 1 year and less than 3 years (3 to 5 doses).
- •Physically and mentally capable of understanding and complying with the study protocol and follow-up.
- •Signed informed consent.
排除标准
- •History of fragility or osteoporotic fracture within the past 12 months.
- •Current or prior treatment within the past 12 months with osteoporosis medications other than denosumab, including Romosozumab, Teriparatide, Alendronate, Ibandronate, Zoledronic acid, Risedronate and Raloxifene.
- •Allergy to bisphosphonates.
- •Secondary osteoporosis.
- •Metabolic bone diseases.
- •Any autoimmune disease.
- •Requirement for long-term use of medications known to affect bone metabolism (e.g., systemic glucocorticoids or hormone therapy).
- •Primary or metastatic bone tumors.
- •Cancer patients, except for in situ carcinoma and non-melanoma skin cancer, unless fully treated and in remission for five years.
- •Hypocalcemia.
- •Vitamin D deficiency (serum 25-hydroxyvitamin D < 25 ng/mL).
- •Renal disease (eGFR < 35 mL/min/1.73 m²) or dialysis patients.
- •Planned dental procedures (e.g., extractions, implants) within the next year.
- •Smoking more than one pack per day (except for those who have quit for over ten years).
研究组 & 干预措施
Ibandronate group
use Ibandronate 1 year and follow-up for 2 years
干预措施: Ibandronate IV (Drug)
Zoledronic acid group
use Zoledronic acid 1 year and follow-up for 2 years
干预措施: Zoledronic acid IV (Drug)
结局指标
主要结局
Percentage change in bone mineral density (BMD)
时间窗: Baseline to 24 months after treatment initiation.
Change in BMD at the lumbar spine, femoral neck, and total hip measured by dual-energy X-ray absorptiometry (DXA) from baseline to 24 months. Baseline is defined as the time point 6 months after the last dose of denosumab, immediately prior to initiation of sequential therapy. BMD measurements will be performed at 6, 12, 18, and 24 months after treatment initiation.
次要结局
- Change in bone turnover makers (BTM) level(Baseline to 24 months)
- Change in visual Analogue Scale (VAS) score(Baseline to 24 months)
- Incidence of osteoporotic fractures(During the intervention period, up to 24 months.)
- Incidence of adverse events (AEs) and serious adverse events (SAEs)(During the intervention period, up to 24 months.)