A 2 x 2 Factorial Randomized Clinical Trial Evaluating Anti-inflammatory and Anti-thrombotic Strategy in Acute Ischemic Stroke
Trial Snapshot
- Phase
- Phase 4
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 4,500
- Primary Endpoint
- Primary efficacy endpoint: Time to cardiovascular death, stroke, myocardial infarction (MI), or urgent arterial
Study Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Matching placebos will be produced for rivaroxaban and colchicine.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Group 4
rivaroxaban placebo BID + colchicine placebo QD
Intervention: Placebo Rivaroxaban (Drug)
Group 2
rivaroxaban 2.5 mg BID + colchicine placebo QD
Intervention: Placebo Colchicine (Drug)
Group 4
rivaroxaban placebo BID + colchicine placebo QD
Intervention: Placebo Colchicine (Drug)
Group 1
rivaroxaban 2.5 mg Twice a day (BID) + colchicine 0.5 mg once daily (QD)
Intervention: Rivaroxaban 2.5 Mg Oral Tablet (Drug)
Group 2
rivaroxaban 2.5 mg BID + colchicine placebo QD
Intervention: Rivaroxaban 2.5 Mg Oral Tablet (Drug)
Group 1
rivaroxaban 2.5 mg Twice a day (BID) + colchicine 0.5 mg once daily (QD)
Intervention: Colchicine 0.5 MG (Drug)
Group 3
rivaroxaban placebo BID + colchicine 0.5 mg QD
Intervention: Colchicine 0.5 MG (Drug)
Group 3
rivaroxaban placebo BID + colchicine 0.5 mg QD
Intervention: Placebo Rivaroxaban (Drug)
Outcomes
Primary Outcomes
Primary efficacy endpoint: Time to cardiovascular death, stroke, myocardial infarction (MI), or urgent arterial
Time Frame: 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
Time Frame: 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
Time Frame: 12 months
Time to first hospitalization for respiratory infections
Secondary Outcomes
- 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)