Clinical trial NCT06396858: Anti-inflammatory and Anti-thrombotic Therapy With colcHicine and Low Dose Rivaroxaban for Major Adverse Cardiovascular Events Reduction in Ischemic Stroke
Official title: A 2 x 2 Factorial Randomized Clinical Trial Evaluating Anti-inflammatory and Anti-thrombotic Strategy in Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Ischemic Stroke
Keywords: Stroke
Anticoagulation
rivaroxaban
colchicine
Lead sponsor: Brazilian Clinical Research Institute
Sponsor class: OTHER
Collaborators: name: Alliança Diagnostic
First posted: 2024-05-02
Enrollment: 4500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
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
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Primary efficacy endpoint: Time to cardiovascular death, stroke, myocardial infarction (MI), or urgent arterial
timeFrame: 12 months
measure: Primary safety endpoint (rivaroxaban versus placebo): Time to major bleeding according to the International Society of Thrombosis and Hemostasis classification
timeFrame: 12 months
measure: Primary safety endpoint (colchicine versus placebo): Hospitalization for respiratory infections
timeFrame: 12 months
Secondary outcomes:
measure: Time to fatal or non-fatal stroke
timeFrame: 12 months
measure: Time to CV death, MI, or stroke
timeFrame: 12 months
measure: Time to death from all causes, MI, or stroke
timeFrame: 12 months
measure: Time to fatal or non-fatal stroke, death, or transient ischemic attack
timeFrame: 12 months
measure: Net clinical endpoint: time to CV death, MI, stroke, fatal bleeding, or critical site bleeding
timeFrame: 12 months
measure: Time to all-cause death
timeFrame: 12 months
Other outcomes:
measure: modified Rankin score
timeFrame: 12 months
measure: Venous thromboembolism
timeFrame: 12 months
measure: New-onset atrial fibrillation
timeFrame: 12 months
measure: Microvascular obstruction at head MRI (substudy)
timeFrame: 12 months
Locations:
Study officials:
affiliation: Brazilian Clinical Research Institute
name: Renato D Lopes, MD, PhD
role: STUDY_CHAIR
References: