Reversion of the Anticoagulant Effect of the New Antithrombotic Agents Anti-Xa and Anti IIa by Specific and Non-specific Haemostatic Drugs,: an Ex-Vivo Study in Healthy Volunteers
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- In vitro Reversal of anticoagulation
研究概览
简要总结
The purpose of this study is to evaluate whether the effect of the two new anticoagulants, Dabigatran and Rivaroxaban, can be reversed by non-specific and specific inhibitors. For Dabigatran the investigators will test the non-specific inhibitors: prothrombin complex concentrate (PCC), recombinant activated coagulation factor VII, and activated prothrombin-complex (FEIBA). For Rivaroxaban the investigators will test a specific Rivaroxaban decoy (FXa-GLAless). This will be done in a laboratory using blood plasma from healthy male volunteers.
详细描述
Background and objective:
Currently the most widely prescribed long term anticoagulant drugs are anti vitamin K agents (AVK). They should be used with caution because they are drugs that have a narrow therapeutic range: the difference between the effective dose and toxic dose is small. Their use thus requires careful laboratory monitoring. They can cause bleeding complications in the case of overdose. The AVKs have two antidotes: Vitamin K and prothrombin complex concentrates (PCC). These reverse the anticoagulant effect.
In recent years, new types of anticoagulants have been marketed in particular Rivaroxaban (Xarelto ®) and Dabigatran (Pradaxa ®). The way they act is different from that of AVK. They have the advantage of having a wider therapeutic range. Their use is therefore easier. They do not require such regular monitoring. However, currently, no antidote has been evaluated to reverse the effect of these anticoagulants in case of emergency.
The purpose of this study is to evaluate whether the effect of the two new anticoagulants can be reversed by non-specific and specific inhibitors. For Dabigatran we will test the non-specific inhibitors prothrombin complex concentrate (PCC), recombinant activated coagulation factor VII, and activated prothrombin complex (FEIBA). For Rivaroxaban we will test a specific Rivaroxaban decoy (FXa-GLAless). This will be done in a laboratory using blood plasma from healthy volunteers.
Methods:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age between 18 and 35 years
- •Subject-free any acute or chronic disease
- •Subjects who signed the written informed consent
- •Subject affiliated to French social security or beneficiary of a similar health insurance scheme
排除标准
- •Any subjects with at least one of the following:
- •Body mass index <19 and > 29
- •Active or being treated for angina, coronary syndrome, stroke or arterial disease
- •Constitutional hemorrhagic disease
- •Acquired bleeding disorder
- •Presenting or treated for any liver disease
- •Abnormal laboratory results for liver function
- •History of venous thrombotic disease
- •History of heparin induced Thrombocytopenia
- •Surgery in the previous month
- •Surgery planned within a month
- •Creatinine clearance below 60 ml / min
- •Clinically significant bleeding or progressive disease at risk of increased bleeding (congenital or acquired hemorrhagic syndromes, uncontrolled severe hypertension, evolving gastrointestinal ulcerative disease, recent history of gastrointestinal ulcer, vascular retinopathy, recent intracranial or intracerebral hemorrhage, intrathecal or intracerebral vascular anomalies, brain, spinal or ophthalmological surgery recently)
- •Hypersensitivity to the active substance or any excipients
- •Person deprived of liberty by judicial or administrative order or person subject to an order of legal protection
- •Refusal of consent
研究组 & 干预措施
Rivaroxaban then Dabigatran
Cross-over study with 15 days between administration of Rivaroxaban and Dabigatran
干预措施: Rivaroxaban, Dabigatran (Drug)
Dabigatran then Rivaroxaban
Cross-over study with 15 days between administration of Dabigatran and Rivaroxaban
干预措施: Dabigatran; Rivaroxaban (Drug)
结局指标
主要结局
In vitro Reversal of anticoagulation
时间窗: just before and 1, 2, 3 and 4 hours after taking medicine
Reversal of anticoagulation by return of thrombin generation time to normal value
次要结局
- In vitro, activated partial thromboplastin time(just before and 1, 2, 3 and 4 hours after taking medicine)