A Survey on the Success of Inhibitor Elimination Using Individualized Concentrate Selection and Controlled (High Dose) Immune Tolerance Induction (ITI)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 300
- 试验地点
- 2
- 主要终点
- The efficacy of ITI, the primary endpoint of this observation, is defined according to the following criteria (The measure is a composite).: Inhibitor titre <0.6 BU, Incremental recovery of FVIII in the normal range,Half-life of FVIII > 7 hours.
研究概览
简要总结
This research program is initiated to evaluate and document data on the success of ITI in 300 haemophilia A patients with newly developed or already existing FVIII-inhibitors (also patients who might potentially have failed in earlier ITIs), which will be treated with ITI - preferably high-dose based on individualized product selection, in order to improve management of this potentially devastating complication of haemophilia treatment.
In order to investigate the role of in vitro tests on individual ITI success rate in patients undergoing ITI, the inhibitor plasma samples can be assayed against different FVIII concentrates using the following in vitro tests: Batch selection, Thrombin generation assay (TGA), Thrombin Generation Test (TGT) to monitor FVIII efficacy, Epitope mapping,IgG Subclasses specific for FVIII, Immunogenotyping.
详细描述
As a result of many technological advances in the last two decades, current factor VIII (FVIII) concentrates (both plasma-derived and recombinant products) are considered very safe in terms of pathogen safety.
The development of inhibitors against FVIII or factor IX (FIX) is considered as a major complication during replacement therapy of haemophiliacs.
Prospective studies of previously untreated patients (PUPs) have suggested that inhibitors develop in up to 33% of patients with moderate to severe haemophilia A. Several strategies are used to control bleedings in such patients, e.g. high-dose treatment with FVIII concentrates, treatment with activated prothrombin complex concentrate (aPCC) or treatment with activated factor VII (FVIIa).
Immune tolerance induction (ITI) in order to eradicate inhibitors in patients suffering from an inhibitor to FVIII with high dose treatment of FVIII was first reported in 1977 by Brackmann & Gormsen in the so-called "Bonn Protocol" and was investigated from then on in a series of clinical studies applying the same or a modified version of the "Bonn Protocol". During these investigations high dose FVIII treatment has been proven efficacious in inducing immune tolerance and was shown to exert a long lasting effect in more than 80 % of the patients treated.
The observational immune tolerance induction research program (ObsITI) will allow a systematic prospective and retrospective data documentation and analysis on the success rate of ITI by using individualized concentrate selection.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Based on the decision of the treating physicians in the participating centres, male patients at any age suffering from severe (FVIII activity < 1%), moderate (FVIII activity >1% - 5%), or mild (FVIII activity > 5%) haemophilia A will be included into this post marketing observation if relevant inhibitor levels (> 0.6 BU) have been detected, or - in case of an inhibitor level <0.6 BU - with reduced recovery or half-life of FVIII.
- •The observation is also open for patients who failed an earlier ITI attempt.
排除标准
- 未提供
结局指标
主要结局
The efficacy of ITI, the primary endpoint of this observation, is defined according to the following criteria (The measure is a composite).: Inhibitor titre <0.6 BU, Incremental recovery of FVIII in the normal range,Half-life of FVIII > 7 hours.
时间窗: one year
The efficacy of ITI, the primary endpoint of this observation, is defined according to the following criteria (The measure is a composite): * Inhibitor titre \<0.6 BU (at least 2 consecutive determinations) * Incremental recovery of FVIII in the normal range (\> 80% of normal) with samples taken prior to and 15 or 30 minutes after FVIII treatment. * Half-life of FVIII \> 7 hours (blood samples for FVIII determination should be taken prior to and 15 or 30 minutes, 1, 2, 4, 8 and either 12 or 24 hours after FVIII treatment. Complete Success: All three criteria above met. Partial Success: Two of the three criteria above met. Partial Response: One of the three criteria above met. Partial Failure of ITI-treatment: Inhibitor still present, but titre has decreased to \<5 BU. Complete Failure of ITI-treatment: None of the above mentioned criteria met, and the inhibitor titre is still ≥5 BU.
次要结局
- The following secondary endpoints will also be evaluated.The measure is a composite.(one year)