An International Randomised Controlled Trial Of Immune Tolerance Induction
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 134
- 试验地点
- 39
- 主要终点
- Success-rate and partial success-rate
研究概览
简要总结
The purpose of this study is to see if a low-dose arm or a high dose-arm of immune tolerance is more effective in eliminating inhibitors in patients with hemophilia A.
详细描述
Subjects will be randomized into a low-dose or high-dose immune tolerance regimen and this study will compare the success rates, the time to achieve tolerance,the complications and the cost of both regimens.It will also aim to identify predictors of successful immune tolerance.
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
- — 至 7 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Severe hemophilia A (FVIII level <1%).
- •A maximum historical inhibitor titer of between 5 BU and 200 BU that must be confirmed once prior to the beginning of ITI.
- •The inhibitor titer should be <10 BU at the start of ITI, confirmed once.
- •The inhibitor must be present for <24 months when ITI begins.
- •Maximum age of 7 at the start of ITI.
- •Willingness to comply with the protocol.
排除标准
- •Moderate or mild hemophilia A (FVIII level >1%).
- •Spontaneous disappearance of the inhibitor prior to ITI.
- •Historical maximum inhibitor titer <5 BU or > 200 BU before starting ITI.
- •Inhibitor titer > 10 BU at the start of ITI.
- •Inhibitor present for more than 24 months before starting ITI.
- •Systemic immunomodulatory drug therapy during immune tolerance e.g. corticosteroids (< 5 days every 2 months maximum dose 2 mg/kg or 60 mg/day), azathioprine, cyclophosphamide, high-dose immunoglobulin or the use of a protein A column or plasmapheresis.
- •Age > 7 years at the start of ITI.
- •Inability or unwillingness to comply with the protocol.
- •Previous attempt at ITI.
研究组 & 干预措施
1
Low-dose treatment (50 FVIII u/kg three times a week).
干预措施: Factor VIII concentrates (Drug)
1
Low-dose treatment (50 FVIII u/kg three times a week).
干预措施: Low-dose treatment (Other)
2
High-dose treatment (200 FVIII u/kg per day).
干预措施: Factor VIII concentrates (Drug)
2
High-dose treatment (200 FVIII u/kg per day).
干预措施: High-dose treatment (Other)
结局指标
主要结局
Success-rate and partial success-rate
时间窗: Up to 69 months
The time from the start of ITI to successful tolerance
时间窗: Up to 33 months
The comparative cost-effectiveness of the two treatment arms
时间窗: Up to 69 months
A comparative assessment of morbidity between the two treatment arms including: number of intercurrent bleeds, infections and number of hospital in-patient days.
时间窗: Up to 69 months
The inhibitor recurrence (relapse) rate in the first twelve months after successful ITI.
时间窗: Up to 45 months
次要结局
- The dose-regimen, success rate and time to ITI,(Up to 69 months)
- The starting inhibitor titre, success rate and time to ITI,(Up to 69 months)
- The peak historical inhibitor titre, success rate and time to ITI,(Up to 69 months)
- The peak inhibitor titre after starting ITI, success rate and time to success,(Up to 69 months)
- The age at the time of inhibitor detection, success-rate and time to success,(Up to 69 months)
- The number of factor VIII treatment days between inhibitor detection and initiation of ITI, success of ITI.(Up to 69 months)
- The type of concentrate used (von Willebrand factor-containing, monoclonal or recombinant), success rate and time to success,(Up to 69 months)
- The effect of interim infections/immunisations, success rate and time to success,(Up to 69 months)
- The effect of treatment interruption, success rate and time to success.(Up to 69 months)