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

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

Status

Not yet recruiting

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06396858

Acronym

ARCHIMEDES

Enrollment

4500

Registered

2024-05-02

Start date

2026-07-01

Completion date

2027-12-01

Last updated

2026-02-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ischemic Stroke

Keywords

Stroke, Anticoagulation, rivaroxaban, colchicine

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.

Interventions

DRUGColchicine 0.5 MG

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

DRUGPlacebo Rivaroxaban

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

DRUGPlacebo Colchicine

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

DRUGRivaroxaban 2.5 Mg Oral Tablet

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

Study design

Allocation

RANDOMIZED

Intervention model

FACTORIAL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

Matching placebos will be produced for rivaroxaban and colchicine.

Intervention model description

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

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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.

Design outcomes

Primary

Measure	Time frame	Description
Primary efficacy endpoint: Time to cardiovascular death, stroke, myocardial infarction (MI), or urgent arterial	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	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	12 months	Time to first hospitalization for respiratory infections

Secondary

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

Contacts

CONTACTRemo Furtado, MD, PhD

remo.furtado@bcri.org.br55 11 59047339

STUDY_CHAIRRenato D Lopes, MD, PhD

Brazilian Clinical Research Institute

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 12, 2026