COlchicine for Left VEntricular Remodeling Treatment in Acute Myocardial Infarction

Myocardial Infarction Clinical Trial

— COVERT-MI  

Official title:

COlchicine for Left VEntricular Remodeling Treatment in Acute Myocardial Infarction, a Phase II, Multicenter, Randomized, Double Blinded, Placebo Controlled Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03156816
• Other study ID #: 69HCL17_0034
• Secondary ID: 2017-004090-13
• Status: Completed
• Phase: Phase 2
• Start date: July 23, 2018
• Est. completion date: August 16, 2021

Study information

• Verified date: January 2022
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Inflammatory processes have been identified as key mediators of ischemia/ reperfusion injury in ST-segment elevation myocardial infarction. They add additional damage to the myocardium and are associated with clinical adverse events (heart failure and cardiovascular death) and poor myocardial recovery. All the different anti-inflammatory approaches to reduce reperfusion injury have been disappointing.

Colchicine is a well-known substance with potent anti-inflammatory properties. In a recent pilot study performed in 151 acute STEMI patients treated with primary percutaneous coronary intervention(PPCI) Deftereos et al. showed a 50% reduction of infarct size (creatine kinase release) with a short course treatment of colchicine in comparison to placebo.

One mechanism to explain this effect could be the reduction of adverse left ventricular (LV) remodelling. LV remodelling is part of the healing process of myocardium after MI. It is defined as the end diastolic volume (EDV) increase in the first months after MI. Adverse LV remodelling is increased by inflammation and ultimately leads to heart failure.

Our main hypothesis is that colchicine with its anti-inflammatory properties significantly reduces the initiation of adverse LV remodelling, together with a significant reduction of infarct size and microvascular obstruction in comparison to placebo in acute STEMI patients referred for PPCI.

After inclusion and randomisation, patients will receive the first part of their experimental treatment: colchicine or placebo before PCI, then, the second part after PCI and during 5 days. They will be followed up during their hospitalization and until one year. In order to evaluate LV remodelling, two cardiac magnetic resonance studies will be performed during their participation: one during their hospitalization and a second at 3 months. At 1 year, adverse events will be collected by phone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 194
• Est. completion date: August 16, 2021
• Est. primary completion date: November 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• All patients, aged over 18 and <80 years,

• Presenting within 12 hours of chest pain onset,

• With ST segment elevation = 0.2 mV in two contiguous leads or new onset of left bundle branch block,

• Referral for primary percutaneous coronary intervention (PPCI).

• Preliminary oral informed consent followed by signed informed consent as soon as possible

• With an initially occluded coronary artery (TIMI angiographic flow of the culprit coronary artery =1)

Exclusion Criteria:

• Patients with any legal protection measure,

• Patients without any health coverage,

• Patients with loss of consciousness or confused

• Patients with a history of prior myocardial infarction

• Patients with cardiogenic shock as defined by a systolic blood pressure <90 mmHg, despite 30 minutes of fluid challenge or requiring intravenous vasoactive agents (dobutamine, noradrenaline, adrenaline)

• Patient with severe liver or known renal dysfunction (known GFR=30 ml/min)

• Patient with known history of severe drug intolerance to colchicine

• Female patients currently pregnant or women of childbearing age not using contraception (oral diagnosis)

• Patients with any obvious contraindication to magnetic resonance imaging (claustrophobia, pace maker, defibrillator….)

• Patients treated by macrolides or pristinamycin

• Chronic treatment with COLCHICINE (Mediterranean familial fever mainly)

• Patient with lactose intolerance

• Patient with swallowing disorders

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• Ventricular Remodeling

Intervention

Drug:
• Colchicine group (experimental arm)
In the experimental group, patients will receive colchicine, starting with a loading dose of 2 mg at the time of revascularization and continuing with 0.5 mg twice daily (b.i.d) for 5 days.
• Placebo group (control arm)
In the placebo group, patients will receive placebo, starting with a loading dose of 2 mg at the time of revascularization and continuing with 0.5 mg twice daily for 5 days.

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire Angers	Angers
France	Hôpital Louis Pradel	Bron
France	Hôpital Saint Joseph	Lyon
France	CHU Arnaud de Villeneuve	Montpellier
France	CHU de Mulhouse	Mulhouse
France	CHU de Poitiers	Poitiers
France	CHU de Rangueil	Toulouse
France	CHRU de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	infarct size (in % of LV mass) as estimated by CMR	The primary endpoint will be the infarct size as estimated by CMR at 5 days follow-up between both groups	5 days
Secondary	LV ejection fraction		At 5 days
Secondary	Microvascular obstruction (in % of LV mass)		At 5 days
Secondary	Absolute adverse left ventricular remodeling (mL)		at 3 months
Secondary	Relative ventricular remodeling (%)		at 3 months
Secondary	Infarct size in % of LV mass	Infarct size in % of LV mass assessed by ce-CMR	At 3 months
Secondary	LVEDV	LVEDV (indexed to body surface area) as determined by CMR at the acute phase and 3 months follow-up respectively	At 3 months
Secondary	LVESV	LVEDV (indexed to body surface area) as determined by CMR at the acute phase and 3 months follow-up respectively	at 3 months
Secondary	Relative LV ejection fraction		5 days
Secondary	Percent of thrombi in the LV		At 5 days
Secondary	Incidence of major adverse cardiovascular events	All cause death, cardiovascular death, heart failure worsening during initial hospitalization, hospitalization for heart failure, non-fatal myocardial infarction, life-threatening ventricular arrhythmias and atrial fibrillation.	at 3 months
Secondary	Incidence of major adverse cardiovascular events	All cause death, cardiovascular death, heart failure worsening during initial hospitalization, hospitalization for heart failure, non-fatal myocardial infarction, life-threatening ventricular arrhythmias and atrial fibrillation.	At 12 months
Secondary	Quality of life assessed by the EuroQol-5D (EQ5D) questionnaire	Evaluation of quality of life by the EQ5D questionnaire ( scale on which the best state is marked 100 and the worst state is marked 0).	At 12 months
Secondary	Dosage of inflammation biomarkers	Dosage of inflammation biomarkers; For all centers: neutrophil count, C-reactive protein, hematology, Platelets, fibrinogen.; For the centers participating to the BioCollection: interleukin 6, interleukin 8, interleukin 1ß and interleukin 18, complement system components.	up to 3 months
Secondary	number of treatment discontinuation		5 days
Secondary	number of adverse events	(diarrhea, nausea/vomiting and myelotoxicity, renal function at 48H).	up to 5 days