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

Sponsor

Azienda USL Toscana Centro (Other)

Overall Status

Recruiting

CT.gov ID

NCT05250596

Collaborator

(none)

175

Enrollment

Locations

Arms

10.2

Anticipated Duration (Months)

58.3

Patients Per Site

5.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non ST Segment Elevation Acute Coronary Syndrome	Drug: Colchicine Drug: Atorvastatin	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

175 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants are assigned to Colchicine plus standard treatment with Atorvastatin or only standard treatment with AtorvastatinParticipants are assigned to Colchicine plus standard treatment with Atorvastatin or only standard treatment with Atorvastatin

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 24, 2022

Anticipated Primary Completion Date :

Sep 24, 2022

Anticipated Study Completion Date :

Dec 30, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

hsCRP change between admission and discharge [Average 4 days: from admission to discharge]
Effect of colchicine plus atorvastatin in limiting hsCRP changes compared to atorvastatin alone

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.