COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction

Myocardial Infarction, Acute Clinical Trial

— COLD-MI  

Official title:

COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04420624
• Other study ID #: 7727
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: December 4, 2020
• Est. completion date: May 24, 2022

Study information

• Verified date: December 2022
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 54
• Est. completion date: May 24, 2022
• Est. primary completion date: May 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• Myocardial Infarction, Acute

Intervention

Drug:
• Colchicine
1 mg (or 0.5mg) tablet of colchicine taken once a day for 1 month

Locations

Country	Name	City	State
France	UH Montpellier	Montpellier

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

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