Targeting TFPI With Concizumab to Improve Haemostasis in Glanzmann Thrombasthenia Patients: an in Vitro Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Effects of mixing concizumab compared with the main bleed treatment options for persons with GT
研究概览
简要总结
Glanzmann thrombasthenia is a rare genetic disorder caused by the absence or the dysfunction of the main receptor present on the surface of platelets, integrin αIIbβ3 or GPIIb-IIIa.
The lack of this protein on the surface of platelets no longer allows these blood cells to bind to each other. This binding corresponds to the process of platelet aggregation.
Generally, local measures will control nasal and superficial bleeding whereas platelet transfusions are used to control or prevent life-threatening.
The main complication of this treatment is the risk of developing anti-αIIbβ3 antibodies directed against the absent protein and platelet transfusion therapy can become ineffective.
Activated recombinant factor VII (rFVIIa) provides an alternative treatment for GT patients who develop such antibodies. However, this therapy has a short duration of efficacy, requiring repeated intravenous administrations every 2 to 3 hours.
There is a new treatment, Concizumab, which has not yet been marketed. This treatment acts on TFPI (tissue factor pathway inhibitor). TFPI is a protein that occurs naturally in the body and prevents blood cells from binding to each other.
Concizumab works by blocking TFPI, which may allow sufficient clotting to prevent bleeding.
This treatment could replace recombinant activated factor VII (rFVIIa) because it has the advantage of a much longer duration of efficacy (about 3 days) and is administered subcutaneously.
详细描述
This is in vitro research. The treatment will be tested on blood samples. This will allow us to evaluate in vitro the ability of Concizumab to restore coagulation compared to the usual treatments of platelet transfusions and recombinant activated factor VII (rFVIIa).
This is a single-center study conducted at the Bordeaux University Hospital, which included 10 with Glanzmann thrombasthenia patients and 10 healthy donors over a period of 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Glanzmann Thrombasthenia Group:
- •Patient ≥18 years old
- •Patient with a clear diagnosis of Glanzmann Thrombasthenia (GT), whatever the subtype of disease
- •Affiliated person or beneficiary of a social security scheme.
- •Free, informed and written consent signed by the participant, and the investigator (at the latest on the day of inclusion and before any examination required by the research)
- •Control Group:
- •Healthy donor ≥ 18 years old
- •Healthy donor, without haemorrhagic ant thrombotic medical history
- •Person should not work in the investigator's department.
- •Affiliated person or beneficiary of a social security scheme
- •Free, informed and written consent signed by the participant, and the investigator (at the latest on the day of inclusion and before any examination required by the research)
排除标准
- •For both patient groups:
- •Patient who has taken aspirin or a nonsteroidal anti-inflammatory medication within the previous 10 days
- •Patient who has received a platelet transfusion or recombinant activated factor VII hemostatic treatment within the previous 7 days
- •Patient who participated in another interventional study involving a drug within 30 days of entering this protocol
- •Psychiatric, social or behavioral condition judged to be non-compatible with the respect of the protocol
- •Adult protected by the law
研究组 & 干预措施
Healthy donors
Healthy donor without haemorrhagic ant thrombotic medical history
干预措施: Global fibrinolytic capacity in PRP using reagents for in vitro triggering of the clot and its lysis (Other)
Glanzmann Thrombasthenia Group
Patient with a clear diagnosis of Glanzmann Thrombasthenia, whatever the subtype of disease
干预措施: Clot formation in whole blood under flow in a microfluidic flow chamber coated with tissue factor and collagen (Other)
Glanzmann Thrombasthenia Group
Patient with a clear diagnosis of Glanzmann Thrombasthenia, whatever the subtype of disease
干预措施: : PRP viscoelastic changes under clot formation measured by thromboelastometry using RoTEM (Other)
Glanzmann Thrombasthenia Group
Patient with a clear diagnosis of Glanzmann Thrombasthenia, whatever the subtype of disease
干预措施: Thrombin Generation Assay (TGA) in PRP using TF trigger (Other)
Glanzmann Thrombasthenia Group
Patient with a clear diagnosis of Glanzmann Thrombasthenia, whatever the subtype of disease
干预措施: Global fibrinolytic capacity in PRP using reagents for in vitro triggering of the clot and its lysis (Other)
Healthy donors
Healthy donor without haemorrhagic ant thrombotic medical history
干预措施: Clot formation in whole blood under flow in a microfluidic flow chamber coated with tissue factor and collagen (Other)
Healthy donors
Healthy donor without haemorrhagic ant thrombotic medical history
干预措施: : PRP viscoelastic changes under clot formation measured by thromboelastometry using RoTEM (Other)
Healthy donors
Healthy donor without haemorrhagic ant thrombotic medical history
干预措施: Thrombin Generation Assay (TGA) in PRP using TF trigger (Other)
Glanzmann Thrombasthenia Group
Patient with a clear diagnosis of Glanzmann Thrombasthenia, whatever the subtype of disease
干预措施: Concizumab (Other)
结局指标
主要结局
Effects of mixing concizumab compared with the main bleed treatment options for persons with GT
时间窗: One point at the inclusion
The samples will be analysed by measurement of in vitro hemostatic capacity : * Clot formation in whole blood under flow (2000 s-1) in a microfluidic flow chamber coated with tissue factor and collagen. Values for Area Under the Curve (Aritrary Unit), Occlusion Starting Time (min), Occlusion Time (min.) will be reported * PRP viscoelastic changes under clot formation measured by thromboelastometry. Values for clot time (sec), clot formation time (sec), maximum clot formation (mm) will be reported * Thrombin Generation Assay in PRP using tissue factor trigger. Values for thrombin activity versus time and the derived parameters incl. lag-time (min.), time to peak (min), time to peak (min), ETP (Arbitrary Unit) will be reported * Global fibrinolytic capacity (Lysis Timer in min) in whole blood using reagents for in vitro triggering of the clot and its lysis
次要结局
未报告次要终点