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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non ST Segment Elevation Acute Coronary Syndrome
• Intervention / Treatment: Drug: Colchicine; Drug: Atorvastatin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 175
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anna Toso, MD; Phone Number: 0039 574 803732; Email: anna.toso@libero.it
• Study Contact Backup: Name: Mario Leoncini, MD; Phone Number: 0039 574 803732; Email: leoncini.mario@tiscali.it

Study Locations

• Italy
  • Pescia, Italy, 59100
    • Recruiting
    • Gaia Chiara Selvaggia Magnaghi
    • Contact: Gaia CS Magnaghi, MD; Phone Number: 0039 572460254; Email: gaiachiaraselvaggia.magnaghi@uslcentro.toscana.it
    • Sub-Investigator: Duccio Rossini, MD
  • Pistoia, Italy, 51100
    • Recruiting
    • Marco Comeglio
    • Contact: Marco Comeglio, MD; Phone Number: 0039 5733521; Email: marco.comeglio@uslcentro.toscana.it
    • Contact: Francesco Biagini, MD; Phone Number: 0039 573351027; Email: francesco.biagini@uslcentro.toscana.it
    • Sub-Investigator: Francesco Biagini, MD
  • Prato, Italy, 59100
    • Recruiting
    • Anna Toso
    • Sub-Investigator: Francesco Bellandi, MD
    • Sub-Investigator: Mauro Maioli, MD
    • Contact: Anna Toso, MD; Phone Number: 0039 574803732; Email: anna.toso@libero.it
    • Sub-Investigator: Mario Leoncini, MD
    • Sub-Investigator: Elisa Vignini, MD
    • Sub-Investigator: Francesco Pestelli, MD
    • Sub-Investigator: Gabriele Grippo, MD
    • Sub-Investigator: Massimiliano Nieri, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Azienda USL Toscana Centro
• Investigators: Principal Investigator: Anna Toso, MD, Santo Stefano Hospital, Prato, Italy

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2022
• Primary Completion (Anticipated): September 24, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: February 20, 2022
• First Posted (Actual): February 22, 2022

Study Record Updates

• Last Update Posted (Actual): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 1, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Acute Coronary Syndrome; Atorvastatin; Acute Kidney Injury; Colchicine; C reactive protein
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Inflammation; Acute Coronary Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Gout Suppressants; Atorvastatin; Colchicine
• Other Study ID Numbers: ID 20426; 2021-000637-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No