Anti-inflammatory and Anti-thrombotic Therapy With colcHicine and Low Dose Rivaroxaban for Major Adverse Cardiovascular Events Reduction in Ischemic Stroke (ARCHIMEDES)

Brazilian Clinical Research Institute

Status and phase: Begins enrollment this month; Phase 4

Conditions: Ischemic Stroke

Treatments: Drug: Rivaroxaban 2.5 Mg Oral Tablet; Drug: Colchicine 0.5 MG; Drug: Placebo Colchicine; Drug: Placebo Rivaroxaban

Study type: Interventional

Funder types: Other

Identifiers

NCT06396858

001/2023

Details and patient eligibility

About

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.

Full 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.

Enrollment: 4,500 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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4,500 participants in 4 patient groups, including a placebo group

Group 1

Active Comparator group

Description:

rivaroxaban 2.5 mg Twice a day (BID) + colchicine 0.5 mg once daily (QD)

Treatment:

Drug: Colchicine 0.5 MG

Drug: Rivaroxaban 2.5 Mg Oral Tablet

Group 2

Active Comparator group

Description:

rivaroxaban 2.5 mg BID + colchicine placebo QD

Treatment:

Drug: Placebo Colchicine

Drug: Rivaroxaban 2.5 Mg Oral Tablet

Group 3

Active Comparator group

Description:

rivaroxaban placebo BID + colchicine 0.5 mg QD

Treatment:

Drug: Placebo Rivaroxaban

Drug: Colchicine 0.5 MG

Group 4

Placebo Comparator group

Description:

rivaroxaban placebo BID + colchicine placebo QD

Treatment:

Drug: Placebo Rivaroxaban

Drug: Placebo Colchicine