RecruitingPhase 3ACTRN12621001408875

The effect of Colchicine on Cardiovascular Outcomes in Stroke Study (The CASPER Study)

Colchicine After Stroke Event to Prevent Event Recurrence (CASPER): A randomised trial to evaluate the efficacy of oral Colchicine in high-risk patients with atherosclerosis-associated inflammation post-Stroke

Sponsor

University of Sydney

Enrollment

1,500 participants

Start Date

Mar 3, 2023

Study Type

Interventional

Conditions

Atherosclerosis Ischemic Stroke Transient Ischemic Attack

Summary

Inflammation is a key component in the cause of ischemic stroke. Colchicine is a commonly used anti-inflammatory medication approved for the treatment of gout, Familial Mediterranean Fever, and acute/recurrent pericarditis. There is an increasing body of evidence in the literature supporting a beneficial role of long-term colchicine therapy in prevention of cardiovascular disease. Low-dose colchicine use has also been proven to be safe, well tolerated and is inexpensive and readily available. The aim of this trial is to assess the effect of low-dose colchicine (0.5mg/daily) in addition to optimal medical therapy of cardiovascular outcomes in stroke patients with evidence of persistent coronary inflammation (based on hs-CRP). We hypothesise that addition of colchicine to optimal medical therapy in patients post-stroke, who have biomarker evidence of persistent inflammation will reduce recurrent cardiovascular events.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria3

Presentation with an ischaemic stroke without major disability (MRS less than or equal to 3 - at time of registration [4-52 weeks]) OR clinical TIA with brain imaging evidence of acute infarction and commenced on OMT
hs-CRP greater than or equal to 1.0mg/L (at time of registration) 4 to 52 weeks post-stroke event
Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments

Exclusion Criteria15

Suspected cardio-embolic stroke/ TIA, that is probably caused by
a. Identified atrial fibrillation (permanent or paroxysmal),
b. Other identified cardiac source (intra-cardiac thrombus, endocarditis, metallic heart valve, low ejection fraction <30%),
c. Stroke/ TIA caused by dissection, endo-carditis, paradoxical embolism, drug use, venous thrombosis, within 48 hours after carotid or cardiac surgery,
Hypercoagulability states,
Migraines related to the index stroke or TIA/ Migrainous Strokes, or inherited cerebrovascular disorders.
Any known intolerance to Colchicine
Pre-existing Colchicine treatment for greater than 7 days within the last 3 months
Current active myopathy with creatine kinase (CK) >3x upper limit of normal.
Severe liver disease or aminotransferase level >3 x upper limit of normal, within the last 3 months
Persistent Blood dyscrasia (white cell count or platelet count <lower limit of normal), within the last 3 months
Estimated glomerular filtration rate (eGFR) <30 ml/min per 1.73m2 at time of registration
Prior or current therapy with a strong CYP3A4 inhibitor or inducer or calcineurin inhibitor
Active autoimmune disease or chronic inflammatory bowel disease (defined as any disease requiring long-term or frequent immunosuppression)
Any other conditions that would not make it possible to participate in the trial

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Interventions

Oral Colchicine 0.5 mg tablet taken daily for median of 3 years. Eligible and consenting participants will be registered and then commenced on Run-In treatment consisting of 1 oral tablet (0.5mg of colchicine) a day for 28 days additional to standard of care. The Run-In treatment will be dispensed to participants in a single blinded manner. Upon completion of the Run-In treatment participants will be asked to return to site for a safety and compliance check before being randomised to receive either oral Colchicine 0.5mg taken daily or matched oral Placebo tablet taken daily for a median of 3 years.