Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 350
- 试验地点
- 46
- 主要终点
- Incident clinical fractures validated by x-ray or other imaging
研究概览
简要总结
Osteogenesis imperfecta (OI) is an inherited skeletal disorder characterised by increased risk of fragility fractures. Bisphosphonates are frequently prescribed for adult patients with OI with the aim of preventing fractures but the evidence base for efficacy is poor. Recent evidence suggests that the bone anabolic agent teriparatide (TPTD) increases bone mineral density (BMD) and may have the potential to prevent fractures in OI.
The purpose of the TOPaZ Trial is to investigate if a a two-year course of teriparatide (TPTD) followed by antiresorptive therapy with a single infusion of zoledronic acid (ZA) in adults with OI reduces the proportion of patients who experience a fracture as compared with standard care
Adult patients with a clinical diagnosis of OI who are willing and able to give informed consent and who do not have contraindications to the study medications will be recruited from participating sites. Participants will be randomised 1:1 to receive either standard care for the duration of the trial or TPTD for 24 months followed by a single infusion of ZA, or another antiresorptive agent in the event that ZA is contraindicated.
Participants will attend recruiting centres for a Baseline/Screening visit, at 12 months, 24 months and at the end of the trial for formal study visits with telephone calls every 6 months from a site research nurse. Participants randomised to TPTD will also attend recruiting centre at regular intervals during the 24 month treatment period to collect new supplies of TPTD.
详细描述
Osteogenesis imperfecta (OI) is an inherited skeletal disorder characterised by increased risk of fragility fractures. Bisphosphonates are frequently prescribed for adult patients with OI with the aim of preventing fractures but the evidence base for efficacy is poor. Recent evidence suggests that the bone anabolic agent teriparatide (TPTD) increases bone mineral density (BMD) and may have the potential to prevent fractures in OI.
The purpose of the TOPaZ Trial is to investigate if a a two-year course of teriparatide (TPTD) followed by antiresorptive therapy with a single infusion of zoledronic acid (ZA) in adults with OI reduces the proportion of patients who experience a fracture as compared with standard care.
The trial has a number of secondary objectives which aim to investigate if a two-year course of TPTD followed by antiresorptive therapy with a single infusion of ZA in adults with OI reduces the total number of fractures, reduces the risk of vertebral fractures; or affects bone pain, quality of life and functional status as compared with standard care. There is also a planned mechanistic analysis to understand which baseline characteristics of adults with OI, such as age, clinical subtype of OI, genetic diagnosis, bone turnover, BMD, and previous treatment influences the occurrence of fractures and/or the response to treatment
Adult patients with a clinical diagnosis of OI who are willing and able to give informed consent and who do not have contraindications to the study medications will be recruited from participating sites. Participants will be randomised 1:1 to receive either standard care for the duration of the trial or TPTD for 24 months followed by a single infusion of ZA, or another antiresorptive agent in the event that ZA is contraindicated. Exclusion criteria include: current or previous treatment with an investigational (non-licensed experimental) drug with effects on bone metabolism, contraindication to TPTD or ZA, women of childbearing potential not using highly effective methods of contraception, pregnancy, women that are breastfeeding or age <18 years.
Participants will attend recruiting centres for a Baseline/Screening visit, at 12 months, 24 months and at the end of the trial for formal study visits with telephone calls every 6 months from a site research nurse. Participants randomised to TPTD will also attend recruiting centre at regular intervals during the 24 month treatment period to collect new supplies of TPTD.
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
- Single (Outcomes Assessor)
盲法说明
Images of incident fractures and vertebral fractures will be assessed by an independent clinical adjudicator blinded to treatment allocation.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients aged 18 years and over with a clinical diagnosis of Osteogenesis Imperfecta (OI)
- •Patients willing and able to consent and comply with the study protocol
排除标准
- •Current or previous treatment with an investigational (non-licensed experimental) drug with effects on bone metabolism
- •Contraindication to teriparatide or zoledronic acid
- •Women of childbearing potential not using highly effective methods of contraception
- •Pregnancy
- •Women that are breastfeeding
- •Age < 18 years
研究组 & 干预措施
Teriparatide and zoledronic acid
Teriparatide (TPTD) 20mcg daily using Teriparatide Pen Injector, given subcutaneously using a self-administered injection device for two years (24 months) followed by a single intravenous 5mg infusion of zoledronic acid.
干预措施: Teriparatide Pen Injector (Drug)
Teriparatide and zoledronic acid
Teriparatide (TPTD) 20mcg daily using Teriparatide Pen Injector, given subcutaneously using a self-administered injection device for two years (24 months) followed by a single intravenous 5mg infusion of zoledronic acid.
干预措施: Zoledronic Acid (Drug)
结局指标
主要结局
Incident clinical fractures validated by x-ray or other imaging
时间窗: Through study completion, approximately 5 years
Proportion of participants experiencing a clinical fracture validated by x-ray or other imaging as compared to standard care
次要结局
- Pain assessed by the Brief Pain Inventory (BPI) Short Form measure(Baseline (0), 12 months, 24 months and Final Trial Visit (5 years after baseline))
- Total number of fractures(Through study completion, approximately 5 years)
- Total number of incident vertebral fractures(Baseline (0) and Final Trial Visit (5 years after baseline))
- Quality of life assessed by the SF-36 (v1) Quality of Life(Baseline, 12 months, 24 months and Final Trial Visit (5 years after baseline)
- Sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI) measure(Baseline (0), 12 months, 24 months and Final Trial Visit (5 years after baseline))
- Functional status assessed by the Health Assessment Questionnaire (HAQ) measure(Baseline (0), 12 months, 24 months and Final Trial Visit (5 years after baseline))
- Adverse events(Through study completion, approximately 5 years)
- Mechanistic analyses (ITT)(Biological samples collected at Baseline (0), 12 months, 24 months and Final Trial Visit (5 years after baseline))