COLchicine On-admission to Reduce Inflammation in Acute Coronary Syndrome (COLOR-ACS)

Study Overview
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Brief Summary
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Since colchicine is known to have anti-inflammatory effects and inflammation is an early component of acute coronary syndrome (ACS), this study aims to evaluate the acute effects of low-dose colchicine, in addition to atorvastatin, administered on-admission to statin-naive patients with non-ST elevation ACS scheduled for early invasive strategy.

Detailed Description
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On-admission all statin naive NSTEACS patients are randomized to receive either standard treatment of atorvastatin 80 mg or standard treatment plus colchicine (1 mg loading dose followed by 0.5 mg/day). Inflammatory biomarker high sensitivity C reactive protein (hs-CRP) is measured in all patients on-admission and every 24 hours thereafter until discharge. Cardiac and renal function parameters are evaluated to evidence the possible beneficial effects of the administration of colchicine in addition to atorvastatin alone both short- and medium-term (up to 30 days). Colchicine tolerance is also investigated through monitoring for clinical side effects.

Official Title
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On-admission Low-dose Colchicine in Addition to Atorvastatin to Reduce Inflammation in Acute Coronary Syndrome

Conditions
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Non ST Segment Elevation Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Colchicine
* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: non-ST elevation acute coronary syndrome; ≥ 18 years; statin-naive. Exclusion Criteria: prior statin therapy and/or colchicine treatment; known allergy or hypersensitivity to colchicine or statins; current treatment with potent inhibitors of CYP3A4 or P-glycoprotein (eg., Cyclosporin, antiretroviral drugs, antimycotics, erythromicin and clarythromycin); previous or scheduled administration of any immunosuppressive therapy; known active malignancy; severe kidney disease (creatinine > 3 mg/dl or dialysis) severe liver disease (ALT and/or AST, > double ref. normal values in case of (a) total bilirubin > double ref. normal values, or (b) alteration in coagulation (INR> 1,5); severe heart failure (NYHA class ≥ 3 or cardiogenic shock) at hospital presentation; severe acute or chronic gastro-intestinal disease (nausea, vomiting, diarrhea, malabsorption disease, malnutrition); pregnancy or lactation; current COVID-19 or other infectious disease; refusal of consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants are assigned to Colchicine plus standard treatment with Atorvastatin or only standard treatment with Atorvastatin
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colchicine and Atorvastatin<br>Colchicine 1 mg (0.5 mg for patients ≤ 70 Kg) on-admission followed by 0.5 mg/day until discharge plus Atorvastatin 80 mg on admission followed by 80 mg/day until discharge. | Drug: Colchicine<br>* Colchicine 1 mg (0.5 mg for patients ≤ 70 Kg) on-admission followed by 0.5 mg/day until discharge.<br>Drug: Atorvastatin<br>* Atorvastatin 80 mg on admission followed by 80 mg/day until discharge.<br>|
| Active Comparator: Atorvastatin<br>Atorvastatin 80 mg on admission followed by 80 mg/day until discharge. | Drug: Atorvastatin<br>* Atorvastatin 80 mg on admission followed by 80 mg/day until discharge.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hsCRP change between admission and discharge | Effect of colchicine plus atorvastatin in limiting hsCRP changes compared to atorvastatin alone | Average 4 days: from admission to discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delta variation in creatinine value from baseline to peak | Delta variation (absolute and relative) in creatinine value from baseline value to peak value | Creatinine value is measured daily during hospitalization - average 4 days | 
| Acute kidney injury incidence | Creatinine increase >= 0.3 mg/dl within 48 hours after angiography | Creatinine value is measured daily during hospitalization - average 4 days | 
| CK-MB peak value | Comparison of CK-MB peak values in the two arms | CK-MB value is measured daily during hospitalization - average 4 days | 
| Glomerular filtration rate changes at 30 days after discharge | Delta variation in the glomerular filtration rate from baseline to 30 days after discharge | Approximately 30 days | 
| Adverse clinical events from admission to 30 days after discharge | Myocardial infarction, glomerular filtration rate deterioration or all-cause death from admission to 30 days after discharge | Approximately 30 days | 
| Tolerance to colchicine | Percentage of patients who do not manifest side effects to colchicine treatment | From admission to discharge - Approximately 4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colchicine, Atorvastatin, Acute Coronary Syndrome, C reactive protein, Acute Kidney Injury