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

Ischemic Stroke Clinical Trial

— ARCHIMEDES  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06396858
• Other study ID #: 001/2023
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: July 2024
• Est. completion date: December 2026

Study information

• Verified date: April 2024
• Source: Brazilian Clinical Research Institute
• Contact: Remo Furtado, MD, PhD
• Phone: 55 11 59047339
• Email: remo.furtado[@]bcri.org.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 4500
• Est. completion date: December 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

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.
• Colchicine 0.5 MG
Patients will receive one tablet, per oral or orogastric route, once a day, for a maximum of 12 months.
• Placebo Rivaroxaban
Patients will receive one tablet, per oral or orogastric route, twice a day, for a maximum of 12 months.
• Placebo Colchicine
Patients will receive one tablet, per oral or orogastric route, once a day, for a maximum of 12 months.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Brazilian Clinical Research Institute	Alliança Diagnostic

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	modified Rankin score	modified Rankin score as ordinal outcome	12 months
Other	Venous thromboembolism	Time to first venous thromboembolism	12 months
Other	New-onset atrial fibrillation	time to new-onset atrial fibrillation	12 months
Other	Microvascular obstruction at head MRI (substudy)	Microvascular obstruction at head MRI (substudy)	12 months
Primary	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	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	Primary safety endpoint (colchicine versus placebo): Hospitalization for respiratory infections	Time to first hospitalization for respiratory infections	12 months
Secondary	Time to fatal or non-fatal stroke	Time to fatal or non-fatal stroke	12 months
Secondary	Time to CV death, MI, or stroke	Time to CV death, MI, or stroke	12 months
Secondary	Time to death from all causes, MI, or stroke	Time to death from all causes, MI, or stroke	12 months
Secondary	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
Secondary	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
Secondary	Time to all-cause death	Time to all-cause death	12 months