Antagonization of Heparin With Protamine Sulfate to Lower All Neurological Ischemic and Hemorrhagic Events After Transcatheter Aortic Valve Implantation for Aortic Stenosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 940
- 试验地点
- 1
- 主要终点
- Composite of ischemic and bleeding events
研究概览
简要总结
Transcatheter aortic valve replacement (TAVR) is now the first therapeutic option offered to high and intermediate risk patients with symptomatic aortic stenosis but even to low-risk, when the aortic valve is tricuspid and the transfemoral approach is suitable. Vascular and bleeding complications are the most frequent procedure-related unwanted events associated with increased short-term morbidity and mortality. Selection of the appropriate vascular access site and pre-closing devices as well as stent implantation mitigate these complications.
ACT-guided heparin reaching a target of 300 seconds or more is recommended prior to the placement of the guiding sheath in the common femoral artery. Protamine sulfate is the heparin antidote, which antagonizes 100% of its anti-IIa activity and 60% of its anti-Xa activity. Reversal of heparin using protamine sulfate is recommended for transapical and complicated transfemoral aortic valve placement.However, there is a great heterogeneity of protamine use in daily practice and supportive evidence for the prevention of bleeding complications as well as its safety is lacking. In addition, the radial approach for the second vascular access is more commonly used as well as the use of echo-guided femoral puncture further questioning reversal of heparin when the procedure has been successfully completed without overt bleeding complications.
Our study aims to demonstrate the superiority of a strategy of systematic ACT-guided heparin administration followed by systematic antagonization with protamine sulfate over usual of care to reduce in-hospital mortality, vascular/bleeding complications, stroke and transcient ischemic attack, myocardial infarction or red blood cell transfusion, from randomization to hospital discharge
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
- Single (Outcomes Assessor)
盲法说明
The members of the endpoint committee will evaluate events related to both primary and secondary outcomes in a blinded manner, ensuring they are unaware of patient identities and the groups to which they were allocated through randomization.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women ≥18 years of age
- •Any patient eligible for transfemoral TAVI, irrespective of the chronic antithrombotic treatment
- •Written informed consent
- •Registered at the French social healthcare
排除标准
- •Any major protamine sulfate exposure contraindications defined as a history of severe pulmonary hypertension, acute pulmonary edema or history of bronchospasm related to protamine sulfate administration
- •Known allergy to protamine sulfate
- •Hypersensitivity to protamine sulfate including protamine contained as an excipient in NPH [Neutral Protamine Hagedorn] insulin, known protamine or protamine-heparine complex antibodies
- •Non-femoral approach for the TAVI procedure
- •Protamine sulfate exposure within 24h of randomization
- •Fish allergy
- •Mechanical valves
- •For men: Sterile or Vasectomy
- •Women of childbearing potential
- •Pregnancy and breast feeding women
- •Contemporaneous enrolment in an interventional clinical trial
- •Patient under guardianship or curatorship
研究组 & 干预措施
Systematic heparine antagonization with protamine sulphate
Complete reversal of the Heparin administered during the TAVI achieved through the infusion of a protamine solution until the ACT returns to its baseline level.
干预措施: Antagonization of heparin with protamine sulfate (Drug)
结局指标
主要结局
Composite of ischemic and bleeding events
时间窗: From procedure to hospital discharge (or at 30 days whichever comes first)
The primary endpoint is defined as the first occurrence, of any event of the composite of all-cause mortality, type 2, 3 or 4 bleeding, major or minor vascular complications, stroke or TIA, myocardial infarction or any redblood transfusion. The primary endpoint will be blindly determined by a clinical event committee according to the valve Academic Research Consortium-3 (VARC-3 classifications)
次要结局
- In hospital stay(From procedure to hospital discharge, assessed up to 30 days)
- Assessement of adverse outcome(From procedure to hospital discharge (or at 30 days whichever comes first))
- Bleeding complication(From procedure to hospital discharge (or at 30 days whichever comes first))
- Assessement of long term adverse outcome(From procedure 12 months post procedure)
- Assessement of interaction(From procedure to hospital discharge (or at 30 days whichever comes first))