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

Sponsor

University Hospital, Montpellier (Other)

Overall Status

Terminated

CT.gov ID

NCT04420624

Collaborator

(none)

Enrollment

Location

Arms

17.6

Actual Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction, Acute	Drug: Colchicine	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

54 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective, phase IIb, monocentric, randomized, open labeled with 2 parallel study arms.Prospective, phase IIb, monocentric, randomized, open labeled with 2 parallel study arms.

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction

Actual Study Start Date :

Dec 4, 2020

Actual Primary Completion Date :

May 24, 2022

Actual Study Completion Date :

May 24, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Percentage of myocardial denervation [6 month]
assess by MIBG (méta-iodobenzylguanidine)-nuclear cardiac imaging

Secondary Outcome Measures

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.
Left Ventricular Ejection Fraction in percent [6 month]
By transthoracic echocardiogram (TTE)
Left Ventricular Ejection Fraction in percent [6 month]
By MIBG (méta-iodobenzylguanidine)-nuclear cardiac imaging
Left Ventricular Ejection Fraction in percent [1 month]
By transthoracic echocardiogram (TTE)
Change in Sinus variability [6 month]
by 24 hours holter recording : SDNN (Standard Deviation of NN intervals) will be measured
Change in Sinus variability [1 month]
by 24 hours holter recording : SDNN (Standard Deviation of NN intervals) will be measured
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 [Between hospitalization and 1 month]
Concentration of NGF ng/mL
Variations in the levels of neurotrophic molecular markers [Between 1 month and 6 months]
Concentration of NGF ng/mL
Variations in the levels of neurotrophic molecular markers [Between hospitalization and 1 month]
Concentration of proNGF ng/mL
Variations in the levels of neurotrophic molecular markers [Between 1 month and 6 months]
Concentration of proNGF ng/mL
Variations in the levels of neurotrophic molecular markers [Between hospitalization and 1 month]
Concentration of BDNF ng/mL
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
Post infarction systemic inflammation evaluation [Between hospitalization and 1 month]
Concentration of biomarkers from blood : CRP (mg/L)
Post infarction systemic inflammation evaluation [Between 1 month and 6 months]
Concentration of biomarkers from blood : CRP (mg/L)
Post infarction systemic inflammation evaluation [Between hospitalization and 1 month]
Concentration of biomarkers from blood : sST2 (ng/mL)
Post infarction systemic inflammation evaluation [Between 1 month and 6 months]
Concentration of biomarkers from blood : sST2 (ng/mL)
Infarct size in percentage of left ventricular [6 month]
Number of Adverse event [from randomization to 6 months]
Comparison of adverse events between 2 arms

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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