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

A 2 x 2 Factorial Randomized Clinical Trial Evaluating Anti-inflammatory and Anti-thrombotic Strategy in Acute Ischemic Stroke

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Rivaroxaban 2.5 Mg Oral Tablet; Drug: Colchicine 0.5 MG; Drug: Placebo Colchicine; Drug: Placebo Rivaroxaban

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 Type: Interventional
• Enrollment (Estimated): 4500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Remo Furtado, MD, PhD; Phone Number: 55 11 59047339; Email: remo.furtado@bcri.org.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1; rivaroxaban 2.5 mg Twice a day (BID) + colchicine 0.5 mg once daily (QD)	Drug: Rivaroxaban 2.5 Mg Oral Tablet; Patients will receive one tablet, per oral or orogastric route, twice a day, for a maximum of 12 months.; Other Names: Xarelto; Drug: Colchicine 0.5 MG; Patients will receive one tablet, per oral or orogastric route, once a day, for a maximum of 12 months.; Other Names: Colchis
Active Comparator: Group 2; rivaroxaban 2.5 mg BID + colchicine placebo QD	Drug: Rivaroxaban 2.5 Mg Oral Tablet; Patients will receive one tablet, per oral or orogastric route, twice a day, for a maximum of 12 months.; Other Names: Xarelto; Drug: Placebo Colchicine; Patients will receive one tablet, per oral or orogastric route, once a day, for a maximum of 12 months.
Active Comparator: Group 3; rivaroxaban placebo BID + colchicine 0.5 mg QD	Drug: Colchicine 0.5 MG; Patients will receive one tablet, per oral or orogastric route, once a day, for a maximum of 12 months.; Other Names: Colchis; Drug: Placebo Rivaroxaban; Patients will receive one tablet, per oral or orogastric route, twice a day, for a maximum of 12 months.
Placebo Comparator: Group 4; rivaroxaban placebo BID + colchicine placebo QD	Drug: Placebo Colchicine; Patients will receive one tablet, per oral or orogastric route, once a day, for a maximum of 12 months.; Drug: Placebo Rivaroxaban; Patients will receive one tablet, per oral or orogastric route, twice a day, for a maximum of 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary efficacy endpoint: Time to cardiovascular death, stroke, myocardial infarction (MI), or urgent arterial	Time to cardiovascular death, stroke, myocardial infarction (MI), or urgent arterial revascularization	12 months
Primary safety endpoint (rivaroxaban versus placebo): Time to major bleeding according to the International Society of Thrombosis and Hemostasis classification	Time to major bleeding according to the International Society of Thrombosis and Hemostasis classification	12 months
Primary safety endpoint (colchicine versus placebo): Hospitalization for respiratory infections	Time to first hospitalization for respiratory infections	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to fatal or non-fatal stroke	Time to fatal or non-fatal stroke	12 months
Time to CV death, MI, or stroke	Time to CV death, MI, or stroke	12 months
Time to death from all causes, MI, or stroke	Time to death from all causes, MI, or stroke	12 months
Time to fatal or non-fatal stroke, death, or transient ischemic attack	Time to fatal or non-fatal stroke, death, or transient ischemic attack	12 months
Net clinical endpoint: time to CV death, MI, stroke, fatal bleeding, or critical site bleeding	Time to CV death, MI, stroke, fatal bleeding, or critical site bleeding	12 months
Time to all-cause death	Time to all-cause death	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin score	modified Rankin score as ordinal outcome	12 months
Venous thromboembolism	Time to first venous thromboembolism	12 months
New-onset atrial fibrillation	time to new-onset atrial fibrillation	12 months
Microvascular obstruction at head MRI (substudy)	Microvascular obstruction at head MRI (substudy)	12 months

Collaborators and Investigators

• Sponsor: Brazilian Clinical Research Institute
• Collaborators: Alliança Diagnostic
• Investigators: Study Chair: Renato D Lopes, MD, PhD, Brazilian Clinical Research Institute

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: April 29, 2024
• First Posted (Actual): May 2, 2024

Study Record Updates

• Last Update Posted (Actual): February 11, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Stroke; Anticoagulation; rivaroxaban; colchicine
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Alkaloids; Morpholines; Oxazines; Thiophenes; Rivaroxaban; Colchicine
• Other Study ID Numbers: 001/2023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No