A Randomized Study of Andexanet Alfa Compared to Usual Care in Patients Receiving a Factor Xa Inhibitor Who Require Urgent Surgery or Procedure (ANNEXA-RS)
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- AstraZeneca
- 入组人数
- 800
- 主要终点
- Number of patients achieving effective intraoperative hemostasis
研究概览
简要总结
The study will aim to find out if the drug andexanet alfa is safe and effective in preventing major bleeding during urgent surgery or invasive procedures. The study will compare the use of andexanet alfa to the usual care given at the study center.
详细描述
This study will be an open-label, randomised, controlled, prospective, multicenter study. The study will include patients requiring urgent surgery or procedure that needs to be performed within 15 hours of the last dose of blood-thinning drug (direct oral activated Factor X (FXa) inhibitor).
The study will comprise of the following periods:
- Screening, followed by surgery or procedure and study intervention.
- Follow-up period: there will be four follow-up visits over a duration of approximately 30 days.
- Follow-up visit for patients with positive anti-andexanet alfa antibody test: patients with a positive anti-andexanet alfa antibody response at day 30 will have a follow-up anti-andexanet alfa antibody test approximately 120 days post-surgery or procedure.
Patients will be randomised in the ratio of 1:1 to receive either andexanet alfa or usual care.
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
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient requires, in the opinion of the Investigator, urgent surgery or procedure and requires reversal of direct oral FXa inhibition.
- •The patient requires urgent surgery or procedure within 12 hours of informed consent.
- •The patient requires urgent surgery or procedure that is expected to be associated with a high risk of bleeding or bleeding to occur into a critical organ.
- •The patient has taken an oral FXa inhibitor (such as apixaban, rivaroxaban, or edoxaban) within 15 hours or more, prior to start of surgery or procedure.
- •Female patients of childbearing potential must have a negative pregnancy test at Screening.
- •Willingness to use highly effective methods of contraception (for male and female patients who are fertile).
排除标准
- •The patient requires surgeries or procedures that have a very low chance of causing significant, uncontrollable bleeding, such as small skin procedures, cataract surgery, and minor dental procedures.
- •The patient has acute life-threatening bleeding at the time of Screening.
- •The patient will undergo a surgery or procedure which will require the use of heparin.
- •Patient who is not expected to live for more than three months due to other health problems or has specifically requested not to be resuscitated if their heart stops beating.
- •Prior to screening, the patient had either experienced low platelet count due to heparin use with or without blood clots or had a genetic condition that affects blood clotting.
- •Patient has acute decompensated heart failure, cardiogenic shock, sepsis, or septic shock at the time of Screening.
- •Patient has history of heparin-induced thrombocytopenia (with or without thrombosis) or inherited coagulopathy (eg, anti-thrombin III deficiency, anti-phospholipid antibody syndrome, protein C/S deficiency, Factor V Leiden) at the time of Screening.
- •Previously diagnosed with a bleeding disorder (eg, platelet function disorder, hemophilia, Von Willebrand disease, or coagulation factor deficiency).
- •Prior known hypersensitivity to andexanet alfa.
- •Use of andexanet alfa 30 days prior to Screening.
- •Patient diagnosed with dementia.
- •Any prohibited medication as determined in the study.
研究组 & 干预措施
Andexanet Alfa Group
Patients will receive andexanet alfa as IV bolus followed by an infusion.
干预措施: Andexanet alfa (Drug)
Usual Care Group
Patients will receive treatment based on the Investigator's discretion, according to regional, local/institutional guidelines or practices.
干预措施: Usual Care (Drug)
结局指标
主要结局
Number of patients achieving effective intraoperative hemostasis
时间窗: From start to the end of surgery or procedure on Day 0
Intraoperative hemostasis will be assessed according to the categories as per 4-point hemostasis scale: Excellent - Normal hemostasis, Good - Mildly abnormal hemostasis (eg. slight oozing from surgical wounds), Moderate - Moderate abnormality in intraprocedural hemostasis (eg. controllable bleeding), Poor - Severe hemostatic abnormality (eg. severe refractory hemorrhage). Hemostasis will be considered to be effective if the intraoperative hemostasis category is 'excellent' or 'good', and ineffective if the intraoperative hemostasis category is 'moderate' or 'poor'.
次要结局
- Change from Baseline in anti-FXa activity measured through blood samples(Baseline to two hours post start of surgery or procedure)