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

NCT06396858 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 001/2023
• Study Type: interventional
• Target: 4,500
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Ischemic Stroke

Keywords

Stroke; Anticoagulation; rivaroxaban; colchicine

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Time to fatal or non-fatal stroke

  12 months

• Time to CV death, MI, or stroke

  12 months

• Time to death from all causes, MI, or stroke

  12 months

• 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

  12 months

Other Outcomes (4)

• modified Rankin score

  12 months

• Venous thromboembolism

  12 months

• New-onset atrial fibrillation

  12 months

Study Arms (4)

Group 1

ACTIVE COMPARATOR

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

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

Group 2

ACTIVE COMPARATOR

rivaroxaban 2.5 mg BID + colchicine placebo QD

Drug: Rivaroxaban 2.5 Mg Oral Tablet; Drug: Placebo Colchicine

Group 3

ACTIVE COMPARATOR

rivaroxaban placebo BID + colchicine 0.5 mg QD

Drug: Colchicine 0.5 MG; Drug: Placebo Rivaroxaban

Group 4

PLACEBO COMPARATOR

rivaroxaban placebo BID + colchicine placebo QD

Drug: Placebo Rivaroxaban; Drug: Placebo Colchicine

Interventions

Rivaroxaban 2.5 Mg Oral Tablet DRUG

Patients will receive one tablet, per oral or orogastric route, twice a day, for a maximum of 12 months.

Also known as: Xarelto

Group 1; Group 2

Colchicine 0.5 MG DRUG

Patients will receive one tablet, per oral or orogastric route, once a day, for a maximum of 12 months.

Also known as: Colchis

Group 1; Group 3

Placebo Rivaroxaban DRUG

Patients will receive one tablet, per oral or orogastric route, twice a day, for a maximum of 12 months.

Group 3; Group 4

Placebo Colchicine DRUG

Patients will receive one tablet, per oral or orogastric route, once a day, for a maximum of 12 months.

Group 2; Group 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brazilian Clinical Research Institute: lead
• Alliança Diagnostic: collaborator

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

Rivaroxaban; Colchicine

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Alkaloids

Study Officials

• Renato D Lopes, MD, PhD

  Brazilian Clinical Research Institute

  STUDY CHAIR

Central Study Contacts

Remo Furtado, MD, PhD

CONTACT

55 11 59047339; remo.furtado@bcri.org.br

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Matching placebos will be produced for rivaroxaban and colchicine.
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: they will be randomized, simultaneously, in a 1:1 ratio, to rivaroxaban 2.5 mg BID or placebo, and colchicine 0.5 mg QD versus placebo, in a 2x2 factorial design. Therefore, the study will have four possible groups: rivaroxaban 2.5 mg BID + colchicine 0.5 mg QD; rivaroxaban 2.5 mg BID + colchicine placebo QD; rivaroxaban placebo BID + colchicine 0.5 mg QD; or rivaroxaban placebo BID + colchicine placebo QD

Study Record Dates

• First Submitted: January 4, 2024
• First Posted: May 2, 2024
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 11, 2026

Record last verified: 2026-02