COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction (COLD-MI)

This study evaluates the benefit of colchicine on induced denervation after myocardial infarction. Patients who have suffered a documented De Novo myocardial infarction and completed a revascularization procedure will receive either colchicine on top of standard therapy, compared to standard therapy alone (1:1 allocation ratio). Colchicine 1mg (or 0.5mg) will be initiated within 48h after percutaneous revascularization and prescribed for one month.

Study Overview

• Status: Terminated
• Conditions: Myocardial Infarction, Acute
• Intervention / Treatment: Drug: Colchicine

Detailed Description

COLD-MI study aims to explore colchicine's impact on myocardial denervation following reperfused acute myocardial infarction. Acute myocardial infarction is the leading cause of heart failure (HF). It induces myocardial denervation predisposing to ventricular rhythm disorders and death. This denervation linked to infarction's size occurs by direct ischaemic mechanisms during the initial coronary occlusion (initially non-vascularised zone) and secondarily by cardiac remodelling in the context of the heart failure (HF). In usual practice, cardiac denervation which intensity is correlated with rhythm and mortality risks, can be evaluated by scintigraphy. In a murine reperfusion model of ischemia, the direct anti-inflammatory effect of colchicine reduces the size of the necrosis and improves post-ischemic remodeling. This suggests that colchicine may reduce myocardial denervation.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34090
    • UH Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age from 18 to 80 year old
• Hospitalization within 12 hours of onset of acute chest pain
• Patient must have suffered a documented acute myocardial infarction
• Coronary occlusion on initial angiography (culprit artery with aTIMI (Thrombolysis in Myocardial Infarction) flow 1 or 0)
• Patient eligible for a revascularization procedure by PTCA (Percutaneous transluminal coronary angioplasty)

Exclusion Criteria:

• Patients with a history of myocardial infarction prior to the current episode
• Patient in cardiogenic shock or with hemodynamic instability
• Patients with severe hepatic or renal dysfunction (GFR ≤30 mL/min)
• Pregnant women or women of childbearing age without contraception
• Treatment with a potent CYP3A4 inhibitor or a P-glycoprotein inhibitor in patients with renal or hepatic impairement
• Association with macrolides (except spiramycin)
• Association with pristinamycin

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colchicine; colchicine and standard therapy	Drug: Colchicine; 1 mg (or 0.5mg) tablet of colchicine taken once a day for 1 month; Other Names: no other name
No Intervention: Comparator; standard therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of myocardial denervation	assess by MIBG (méta-iodobenzylguanidine)-nuclear cardiac imaging	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the heart-to-mediastinum ratio	The heart-to-mediastinum (H/M) ratio, the heart count normalized for the mediastinum count, is used as a quantitative index in cardiac 123 I-MIBG imaging.	6 month
Left Ventricular Ejection Fraction in percent	By transthoracic echocardiogram (TTE)	6 month
Left Ventricular Ejection Fraction in percent	By MIBG (méta-iodobenzylguanidine)-nuclear cardiac imaging	6 month
Left Ventricular Ejection Fraction in percent	By transthoracic echocardiogram (TTE)	1 month
Change in Sinus variability	by 24 hours holter recording : SDNN (Standard Deviation of NN intervals) will be measured	6 month
Change in Sinus variability	by 24 hours holter recording : SDNN (Standard Deviation of NN intervals) will be measured	1 month
Basic ECG parameters (QRS duration)		6 month
Basic ECG parameters (QRS duration)		1 month
Basic ECG parameters (corrected QT)		1 month
Basic ECG parameters (corrected QT)		6 month
Number of ventricular extrasystole (2 or 3 VES) per 24 hours on the Holter		6 month
Number of bursts (2 or 3 VES) per 24 hours on the Holter		1 month
Number of bursts (2 or 3 VES) per 24 hours on the Holter		6 month
Number of ventricular or supraventricular tachycardia (>3 VES) episodes per 24 hours		1 month
Number of ventricular or supraventricular tachycardia (>3 VES) episodes per 24 hours		6 month
Time from randomization to death (total mortality)		6 month
Time from randomization to heart failure hospitalization		6 month
Time from randomization to all-cause hospitalization		6 month
Variations in the levels of neurotrophic molecular markers	Concentration of NGF ng/mL	Between hospitalization and 1 month
Variations in the levels of neurotrophic molecular markers	Concentration of NGF ng/mL	Between 1 month and 6 months
Variations in the levels of neurotrophic molecular markers	Concentration of proNGF ng/mL	Between hospitalization and 1 month
Variations in the levels of neurotrophic molecular markers	Concentration of proNGF ng/mL	Between 1 month and 6 months
Variations in the levels of neurotrophic molecular markers	Concentration of BDNF ng/mL	Between hospitalization and 1 month
Variations in the levels of neurotrophic molecular markers	Concentration of BDNF ng/mL	Between 1 month and 6 months
Biological evaluation of infarction size Creatine PhosphoKinase (CPK)	Area Under Curve (AUC) of CPK	During hospitalization (Day 1 to Day 5)
Biological evaluation of infarction size (troponin)	Area Under Curve (AUC) of Troponin	During hospitalization (Day 1 to Day 5)
Post infarction systemic inflammation evaluation	Concentration of biomarkers from blood : CRP (mg/L)	Between hospitalization and 1 month
Post infarction systemic inflammation evaluation	Concentration of biomarkers from blood : CRP (mg/L)	Between 1 month and 6 months
Post infarction systemic inflammation evaluation	Concentration of biomarkers from blood : sST2 (ng/mL)	Between hospitalization and 1 month
Post infarction systemic inflammation evaluation	Concentration of biomarkers from blood : sST2 (ng/mL)	Between 1 month and 6 months
Infarct size in percentage of left ventricular		6 month
Number of Adverse event	Comparison of adverse events between 2 arms	from randomization to 6 months

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2020
• Primary Completion (Actual): May 24, 2022
• Study Completion (Actual): May 24, 2022

Study Registration Dates

• First Submitted: April 29, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): December 15, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Heart failure; Myocardial infarction; Sympathetic denervation
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 7727

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