Thrombin Generation Assay (TGA) as Predictive Test for Haemostatic Effectiveness of Factor VIII (FVIII) Concentrates in Patients Affected by Inherited Haemophilia A With FVIII Inhibitors High and Low Anamnestic Response.
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 25
- 试验地点
- 15
- 主要终点
- Thrombin generation result
研究概览
简要总结
This is an observational, prospective, longitudinal, multicenter, cohort study designed with the scope to verify whether or not TGA may predict effectiveness of different FVIII concentrates class (devoid or rich of VWF) in patient affected by severe or moderately severe inherited haemophilia A and inhibitors.
详细描述
Rationale:
Hemophilia A is a serious and common hereditary bleeding disorder caused by deficiency of coagulation factor VIII (FVIII). Patients with this disease are treated with recombinant factor VIII or factor VIII concentrates derived from plasma.
Administration of exogenous FVIII in 15-35% of cases, cause the formation of antibodies to FVIII (inhibitors) that neutralize the activity of factor VIII, making the treatment ineffective.The development of inhibitors of factor VIII (FVIII) is the most serious and challenging complication of the treatment of hemophilia A and represents the highest economic burden for a chronic disease. Therefore, research is making great efforts to optimize the best therapeutic approach for the disease.
It has been observed that FVIII inhibitors display a wide range of immunoreactivity when tested against different classes of FVIII concentrates (with/without von Willebrand factor -VWF). It has been demonstrated that the different inhibitors reactivity may correlate with different ability of inhibitors to impair thrombin generation, as tested by Thrombin Generation Assay (TGA). In these patients TGA assay might be a tool to predict which FVIII concentrate has the greater haemostatic effectiveness.
It is also uncertain if the different classes of FVIII used in ITI protocols may have a different effectiveness in reducing the occurrence of BT bleedings and if this may correlate to lower reactivity, epitope specificity, VWF content and may be predicted by TGA. It would be very helpful to be able to give an evidence based diagnostic and prognostic instrument, the TGA, to aid physician to optimize the therapy for all inhibitors patients.
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
- •Diagnosis of inherited, severe (FVIII:C < 1%) or moderately severe haemophilia A (FVIII ≤ 2%)
- •Ability to comply with study methods and willingness to participate to the study
- •Written informed consent.
- •FOR THE LOW RESPONDERS COHORT
- •Documented low anamnestic response after FVIII exposure (FVIII inhibitors titre >0.6 and < 5 BU/ml tested by Bethesda assay, Nijmegen modification). It will be included in this study those patients who have never been submitted to ITI and also those patients who have completed ITI with partial success (defined as inhibitors titre >0.6 and < 5 BU/ml and no increase in the INH titer > 5 BU over treatment with FVIII)
- •INCLUSION CRITERIA FOR THE HIGH RESPONDERS COHORT
- •Documented high response after FVIII exposure (FVIII inhibitors titre > 5 BU/ml tested by Bethesda assay, Nijmegen modification). It will be included in this study those patients who are potential candidates to a first or rescue ITI.
- •Any historical peak ≥ 5 BU
排除标准
- •Diagnosis of acquired haemophilia
- •Diagnosis of inherited mild haemophilia A (FVIII > 2%)
- •Life expectancy lower than 1 year
- •Psychiatric illness and any other conditions may impair ability to comply with study methods
结局指标
主要结局
Thrombin generation result
时间窗: 12 months
Thrombin generation results of the TGA applied on plasma patients whith inhibitor matched with different class of FVIII concentrate
次要结局
- Incidence of all breakthrough (BT) bleedings(12 months)
- Total FVIII dose required to treat the patients(12 months)
- Use of bypassing agents(12 months)
- ITI outcome only for patient under this kind of treatment(3 years)
- Epitope mapping results(12 months)
- the inhibitor titre course(12 months)