Clinical trial NCT04420624: COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction
Official title: COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Myocardial Infarction, Acute
Keywords: Myocardial infarction
Sympathetic denervation
Heart failure
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2020-06-09
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, phase IIb, monocentric, randomized, open labeled with 2 parallel study arms.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of myocardial denervation
timeFrame: 6 month
Secondary outcomes:
measure: Change in the heart-to-mediastinum ratio
timeFrame: 6 month
measure: Left Ventricular Ejection Fraction in percent
timeFrame: 6 month
measure: Left Ventricular Ejection Fraction in percent
timeFrame: 6 month
measure: Left Ventricular Ejection Fraction in percent
timeFrame: 1 month
measure: Change in Sinus variability
timeFrame: 6 month
measure: Change in Sinus variability
timeFrame: 1 month
measure: Basic ECG parameters (QRS duration)
timeFrame: 6 month
measure: Basic ECG parameters (QRS duration)
timeFrame: 1 month
measure: Basic ECG parameters (corrected QT)
timeFrame: 1 month
measure: Basic ECG parameters (corrected QT)
timeFrame: 6 month
measure: Number of ventricular extrasystole (2 or 3 VES) per 24 hours on the Holter
timeFrame: 6 month
measure: Number of bursts (2 or 3 VES) per 24 hours on the Holter
timeFrame: 1 month
measure: Number of bursts (2 or 3 VES) per 24 hours on the Holter
timeFrame: 6 month
measure: Number of ventricular or supraventricular tachycardia (>3 VES) episodes per 24 hours
timeFrame: 1 month
measure: Number of ventricular or supraventricular tachycardia (>3 VES) episodes per 24 hours
timeFrame: 6 month
measure: Time from randomization to death (total mortality)
timeFrame: 6 month
measure: Time from randomization to heart failure hospitalization
timeFrame: 6 month
measure: Time from randomization to all-cause hospitalization
timeFrame: 6 month
measure: Variations in the levels of neurotrophic molecular markers
timeFrame: Between hospitalization and 1 month
measure: Variations in the levels of neurotrophic molecular markers
timeFrame: Between 1 month and 6 months
measure: Variations in the levels of neurotrophic molecular markers
timeFrame: Between hospitalization and 1 month
measure: Variations in the levels of neurotrophic molecular markers
timeFrame: Between 1 month and 6 months
measure: Variations in the levels of neurotrophic molecular markers
timeFrame: Between hospitalization and 1 month
measure: Variations in the levels of neurotrophic molecular markers
timeFrame: Between 1 month and 6 months
measure: Biological evaluation of infarction size Creatine PhosphoKinase (CPK)
timeFrame: During hospitalization (Day 1 to Day 5)
measure: Biological evaluation of infarction size (troponin)
timeFrame: During hospitalization (Day 1 to Day 5)
measure: Post infarction systemic inflammation evaluation
timeFrame: Between hospitalization and 1 month
measure: Post infarction systemic inflammation evaluation
timeFrame: Between 1 month and 6 months
measure: Post infarction systemic inflammation evaluation
timeFrame: Between hospitalization and 1 month
measure: Post infarction systemic inflammation evaluation
timeFrame: Between 1 month and 6 months
measure: Infarct size in percentage of left ventricular
timeFrame: 6 month
measure: Number of Adverse event
timeFrame: from randomization to 6 months
Other outcomes:
Locations:
city: Montpellier
country: France
facility: UH Montpellier
Study officials:
References: