A 2 x 2 Factorial Randomized Clinical Trial Evaluating Anti-inflammatory and Anti-thrombotic Strategy in Acute Ischemic Stroke
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 4,500
- 主要终点
- Primary efficacy endpoint: Time to cardiovascular death, stroke, myocardial infarction (MI), or urgent arterial
研究概览
简要总结
The ARCHIMEDES study (Anti-inflammatory and anti-thRombotic therapy with colCHicine and low dose rIvaroxaban for Major adverse cardiovascular Events reDuction in ischEmic Stroke) will be a randomized, double-blind, 2x2 factorial clinical trial, which will include at least 3000 and up to a maximum of 4500 patients with ischemic stroke without indication of oral anticoagulation.
详细描述
In patients with ischemic stroke, within 14 days of symptom onset, to establish the efficacy and safety of two strategies in parallel: low-dose rivaroxaban and low-dose colchicine, compared with placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Matching placebos will be produced for rivaroxaban and colchicine.
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
- •Patients with acute ischemic stroke aged ≥18 years old who, regardless of etiology and mechanism, do not have a definitive indication for anticoagulation, and whose symptoms onset has been within the last 14 days;
- •Receiving standard therapy for acute management of ischemic stroke;
- •For patients treated with fibrinolytics, a minimum period of 24 hours after the infusion of the lytic drug is required for randomization into the study.
排除标准
- •Modified Rankin score of 4 or more at randomization;
- •Refusal to provide consent;
- •Severe renal failure, with glomerular filtration rate (by CKD-EPI) estimated at <15 mL/min/1.73 m2;
- •Severe liver failure (child C);
- •Indication for full-dose anticoagulation (for example, venous thromboembolism or atrial fibrillation);
- •Previous hemorrhagic stroke or history of intracranial hemorrhage;
- •Systemic treatment with a potent CYP 3A4 inhibitor (such as azole antifungals and protease inhibitors), or with a potent 3A4 inducer (such as rifampicin, phenytoin, phenobarbital, or carbamazepine);
- •History of inflammatory bowel disease or chronic diarrhea;
- •Prolonged treatment (> 1 month) with immunosuppressants or systemic corticosteroids;
- •History of recurrent pneumonia (3 or more hospitalizations in the last 12 months);
- •Pregnancy or breastfeeding;
- •Any other comorbidity other than stroke and CV disease (e.g., metastatic cancer) that, in the investigator's opinion, has a significant impact on the 12-month survival.
研究组 & 干预措施
Group 4
rivaroxaban placebo BID + colchicine placebo QD
干预措施: Placebo Rivaroxaban (Drug)
Group 2
rivaroxaban 2.5 mg BID + colchicine placebo QD
干预措施: Placebo Colchicine (Drug)
Group 4
rivaroxaban placebo BID + colchicine placebo QD
干预措施: Placebo Colchicine (Drug)
Group 1
rivaroxaban 2.5 mg Twice a day (BID) + colchicine 0.5 mg once daily (QD)
干预措施: Rivaroxaban 2.5 Mg Oral Tablet (Drug)
Group 2
rivaroxaban 2.5 mg BID + colchicine placebo QD
干预措施: Rivaroxaban 2.5 Mg Oral Tablet (Drug)
Group 1
rivaroxaban 2.5 mg Twice a day (BID) + colchicine 0.5 mg once daily (QD)
干预措施: Colchicine 0.5 MG (Drug)
Group 3
rivaroxaban placebo BID + colchicine 0.5 mg QD
干预措施: Colchicine 0.5 MG (Drug)
Group 3
rivaroxaban placebo BID + colchicine 0.5 mg QD
干预措施: Placebo Rivaroxaban (Drug)
结局指标
主要结局
Primary efficacy endpoint: Time to cardiovascular death, stroke, myocardial infarction (MI), or urgent arterial
时间窗: 12 months
Time to cardiovascular death, stroke, myocardial infarction (MI), or urgent arterial revascularization
Primary safety endpoint (rivaroxaban versus placebo): Time to major bleeding according to the International Society of Thrombosis and Hemostasis classification
时间窗: 12 months
Time to major bleeding according to the International Society of Thrombosis and Hemostasis classification
Primary safety endpoint (colchicine versus placebo): Hospitalization for respiratory infections
时间窗: 12 months
Time to first hospitalization for respiratory infections
次要结局
- Net clinical endpoint: time to CV death, MI, stroke, fatal bleeding, or critical site bleeding(12 months)
- Time to fatal or non-fatal stroke, death, or transient ischemic attack(12 months)
- Time to death from all causes, MI, or stroke(12 months)
- Time to CV death, MI, or stroke(12 months)
- Time to fatal or non-fatal stroke(12 months)
- Time to all-cause death(12 months)