COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction

Phase 2

Terminated

• Conditions: Myocardial Infarction, Acute
• Interventions: Drug: Colchicine

• Registration Number: NCT04420624
• Lead Sponsor: University Hospital, Montpellier

Brief Summary

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.

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 Timeline

• Study First Submitted: 2020-04-29
• Study First Submitted QC: 2020-06-05
• Study First Posted: 2020-06-09
• Study Start: 2020-12-04
• Primary Completion: 2022-05-24
• Study Completion: 2022-05-24
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-14
• Last Update Posted: 2022-12-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 54

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Colchicine	Colchicine	colchicine and standard therapy

Primary Outcome Measures

Name	Time	Method
Percentage of myocardial denervation	6 month	assess by MIBG (méta-iodobenzylguanidine)-nuclear cardiac imaging

Secondary Outcome Measures

Name	Time	Method
Change in Sinus variability	1 month	by 24 hours holter recording : SDNN (Standard Deviation of NN intervals) will be measured
Time from randomization to heart failure hospitalization	6 month
Time from randomization to all-cause hospitalization	6 month
Change in the heart-to-mediastinum ratio	6 month	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.
Basic ECG parameters (corrected QT)	6 month
Time from randomization to death (total mortality)	6 month
Left Ventricular Ejection Fraction in percent	1 month	By transthoracic echocardiogram (TTE)
Variations in the levels of neurotrophic molecular markers	Between 1 month and 6 months	Concentration of BDNF ng/mL
Biological evaluation of infarction size Creatine PhosphoKinase (CPK)	During hospitalization (Day 1 to Day 5)	Area Under Curve (AUC) of CPK
Biological evaluation of infarction size (troponin)	During hospitalization (Day 1 to Day 5)	Area Under Curve (AUC) of Troponin
Basic ECG parameters (QRS duration)	1 month
Number of ventricular extrasystole (2 or 3 VES) per 24 hours on the Holter	6 month
Number of ventricular or supraventricular tachycardia (>3 VES) episodes per 24 hours	6 month
Number of bursts (2 or 3 VES) per 24 hours on the Holter	6 month
Infarct size in percentage of left ventricular	6 month
Post infarction systemic inflammation evaluation	Between 1 month and 6 months	Concentration of biomarkers from blood : sST2 (ng/mL)
Number of Adverse event	from randomization to 6 months	Comparison of adverse events between 2 arms

Trial Locations

Locations (1)

UH Montpellier; 🇫🇷 Montpellier, France