Better Evidence and Translation for Calciphylaxis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 350
- 试验地点
- 21
- 主要终点
- BEAT-Calci Wound Assessment Scale (BCWAS) - Baseline to Week 12
研究概览
简要总结
This global platform study will evaluate multiple interventions, across several domains of therapeutic care, in adult patients with kidney failure and newly diagnosed calciphylaxis.
详细描述
BEAT-Calci is a randomized, adaptive, multi-center, platform trial that will evaluate multiple interventions, across several domains of therapeutic care. The objective of the study is to establish high-quality evidence on the effect of a range of interventions in patients with kidney failure and newly diagnosed calciphylaxis. Calciphylaxis is a rare disease affecting 1-2 people in 10,000.
The trial will commence with a Dialysis Membrane Domain and Pharmacotherapy Domain. The Pharmacotherapy Domain of BEAT-Calci is a placebo-controlled, double blind, response adaptive, randomised controlled trial that will investigate whether any of the pharmacotherapeutic agents is superior to placebo in improving outcomes. The Dialysis Membrane Domain of BEAT-Calci is an open-label, randomised controlled two-way comparison between two different dialysis technologies.
The BEAT-Calci Wound Assessment Scale (BCWAS) is the primary endpoint for the trial. It is an 8-point ordinal categorical scale of disease outcomes and will be used to determine each participant's outcome.
The trial will utilise a Bayesian adaptive sample size re-estimation approach for sample size calculations. The trial will continue to recruit until predefined superiority or futility rules are met. As the trial progresses, in response to information accumulating during the trial, there are various adaptations that can occur, including addition or removal of an intervention arm, response adaptive randomisation and addition of new therapeutic domains.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Blinding of all parties will not be possible for all domains. The default position of the BEAT-Calci platform is that treatments determined by randomization will be blinded to as high a level is feasible.
Within practical domains, a blind will be adopted, whereby participants, site personnel, trial investigators and outcome assessors will remain blinded to the treatment from the time of randomization until database lock of the comparisons to which that participant is contributing data. In blinded domains, randomization data will not be accessible by anyone else involved in the trial with the following exceptions: (1) data managers who work on the randomization and drug management system, (2) unblinded statistician(s) involved with the response adaptive randomization, and (3) the unblinded biostatistician who prepares reports for the IDMC. Information on the blind, or lack thereof, per domain will be described in the respective Domain-Specific Appendix.
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
- •Currently receiving haemodialysis, or peritoneal dialysis that can be converted to haemodialysis, with planned ongoing haemodialysis a minimum of three times per week for at least the duration of the protocolised calciphylaxis treatments within this trial
- •Have a new calciphylaxis ulcer present for less than 10 weeks
- •Age ≥ 18 years
- •Eligible for randomisation in at least one recruiting domain
- •The participant and treating physician are willing and able to perform trial procedures
排除标准
- 未提供
研究组 & 干预措施
Placebo (Double-Blind Period)
Placebo Vitamin K1 Placebo Magnesium Citrate Placebo Sodium Thiosulphate
干预措施: Placebo injection (normal saline) (Drug)
Placebo (Double-Blind Period)
Placebo Vitamin K1 Placebo Magnesium Citrate Placebo Sodium Thiosulphate
干预措施: Placebo capsule (Vitamin K1) (Drug)
Placebo (Double-Blind Period)
Placebo Vitamin K1 Placebo Magnesium Citrate Placebo Sodium Thiosulphate
干预措施: Placebo tablet (Magnesium citrate) (Drug)
Vitamin K1 (Double-Blind Period)
Dose: 10mg Vitamin K1 capsules, administered 3 times per week following the subject's hemodialysis session.
- Placebo Magnesium Citrate
- Placebo Sodium Thiosulphate
干预措施: Vitamin K1 (Drug)
Vitamin K1 (Double-Blind Period)
Dose: 10mg Vitamin K1 capsules, administered 3 times per week following the subject's hemodialysis session.
- Placebo Magnesium Citrate
- Placebo Sodium Thiosulphate
干预措施: Placebo injection (normal saline) (Drug)
Vitamin K1 (Double-Blind Period)
Dose: 10mg Vitamin K1 capsules, administered 3 times per week following the subject's hemodialysis session.
- Placebo Magnesium Citrate
- Placebo Sodium Thiosulphate
干预措施: Placebo tablet (Magnesium citrate) (Drug)
Magnesium Citrate (Double-Blind Period)
Dose: 150mg Magnesium Citrate tablets, administered 3 times per day. On dialysis days, administration of the middle daily dose should occur following the subject's hemodialysis session.
- Placebo Vitamin K1
- Placebo Sodium Thiosulphate
干预措施: Magnesium citrate (Drug)
Magnesium Citrate (Double-Blind Period)
Dose: 150mg Magnesium Citrate tablets, administered 3 times per day. On dialysis days, administration of the middle daily dose should occur following the subject's hemodialysis session.
- Placebo Vitamin K1
- Placebo Sodium Thiosulphate
干预措施: Placebo injection (normal saline) (Drug)
Magnesium Citrate (Double-Blind Period)
Dose: 150mg Magnesium Citrate tablets, administered 3 times per day. On dialysis days, administration of the middle daily dose should occur following the subject's hemodialysis session.
- Placebo Vitamin K1
- Placebo Sodium Thiosulphate
干预措施: Placebo capsule (Vitamin K1) (Drug)
Sodium Thiosulfate (Double-Blind Period)
Dose: 25g Sodium Thiosulfate injection, administered intravenously 3 times per week, during the subject's last hour of hemodialysis.
- Placebo Vitamin K1
- Placebo Magnesium Citrate
干预措施: Sodium Thiosulfate (Drug)
Sodium Thiosulfate (Double-Blind Period)
Dose: 25g Sodium Thiosulfate injection, administered intravenously 3 times per week, during the subject's last hour of hemodialysis.
- Placebo Vitamin K1
- Placebo Magnesium Citrate
干预措施: Placebo capsule (Vitamin K1) (Drug)
Sodium Thiosulfate (Double-Blind Period)
Dose: 25g Sodium Thiosulfate injection, administered intravenously 3 times per week, during the subject's last hour of hemodialysis.
- Placebo Vitamin K1
- Placebo Magnesium Citrate
干预措施: Placebo tablet (Magnesium citrate) (Drug)
High Flux Hemodialysis
Hemodialysis using a high flux dialyser
干预措施: High Flux Dialyser (Device)
Medium Cut-off Hemodialysis
Hemodialysis using a medium cut-off dialyser
干预措施: Medium Cut-off Dialyser (Device)
结局指标
主要结局
BEAT-Calci Wound Assessment Scale (BCWAS) - Baseline to Week 12
时间窗: Week 12
To determine whether addition of the intervention changes the sentinel ulcer from Baseline to Week 12 on the BEAT-Calci Wound Assessment Scale. This is an 8-point ordinal categorical scale of change since baseline, which will be used to determine each participant's outcome. The scale is described as: 1. Complete epithelialisation of the sentinel ulcer 2. \>50% reduction in sentinel ulcer surface area 3. 20-50% reduction in sentinel ulcer surface area 4. 0-20% reduction in sentinel ulcer surface area 5. Any increase in sentinel ulcer surface area 6. Development of new ulcers 7. Amputation due to an ulcer 8. All-cause death
次要结局
- Distribution of each of the individual components of the BCWAS, assessed at Week 12(Week 12)
- Change over time of self-reported pain(Week 26)
- Sentinel ulcer surface area - from Baseline, assessed at Week 4(Week 4)
- Sentinel ulcer surface area - from Baseline, assessed at Week 26(Week 26)
- All ulcers total surface area - from Baseline, assessed at Week 4(Week 4)
- Bates-Jensen Wound Assessment Tool - from Baseline to Week 26(Week 26)
- Distribution of each of the individual components of the BCWAS, assessed at Weeks 4(Week 4)
- Distribution of each of the individual components of the BCWAS, assessed at Week 26(Week 26)
- Bates-Jensen Wound Assessment Tool - from Baseline to Week 4(Week 4)
- Self-reported pain at week 12(Week 12)
- BEAT-Calci Wound Assessment Scale - Baseline to Week 26(Week 26)
- Bates-Jensen Wound Assessment Tool - from Baseline to Week 12(Week 12)
- Sentinel ulcer surface area - from Baseline, assessed at Week 12(Week 12)
- All ulcers total surface area - from Baseline, assessed at Week 26(Week 26)
- Composite self-reported pain and analgesic use at week 12(Week 12)
- Change in self-reported quality of life from Baseline to Week 4(Week 4)
- Change in self-reported quality of life from Baseline to Week 12(Week 12)
- Change in self-reported quality of life from Baseline to Week 26(Week 26)
- All ulcers total surface area - from Baseline, assessed at Week 12(Week 12)
- Change over time of analgesic use(Week 26)
- Analgesic use week 12(Week 12)
- Time to first calciphylaxis-attributable infection from Baseline to Week 26(Week 26)
- Mortality(Up to 5 years)
- Kidney Transplantation(Up to 5 years)
- Calciphylaxis recurrence(Up to 5 years)
- Composite self-reported pain and analgesic use over time(Week 26)
- All-cause hospitalisation days(Weeks 0-26)