Clinical trial NCT03156816: COlchicine for Left VEntricular Remodeling Treatment in Acute Myocardial Infarction
Official title: COlchicine for Left VEntricular Remodeling Treatment in Acute Myocardial Infarction, a Phase II, Multicenter, Randomized, Double Blinded, Placebo Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myocardial Infarction
Keywords: Myocardial Infarction
STEMI
Inflammation
Left ventricular remodeling
Colchicine
CMR
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2017-05-17
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: infarct size (in % of LV mass) as estimated by CMR
timeFrame: 5 days
Secondary outcomes:
measure: LV ejection fraction
timeFrame: At 5 days
measure: Microvascular obstruction (in % of LV mass)
timeFrame: At 5 days
measure: Absolute adverse left ventricular remodeling (mL)
timeFrame: at 3 months
measure: Relative ventricular remodeling (%)
timeFrame: at 3 months
measure: Infarct size in % of LV mass
timeFrame: At 3 months
measure: LVEDV
timeFrame: At 3 months
measure: LVESV
timeFrame: at 3 months
measure: Relative LV ejection fraction
timeFrame: 5 days
measure: Percent of thrombi in the LV
timeFrame: At 5 days
measure: Incidence of major adverse cardiovascular events
timeFrame: at 3 months
measure: Incidence of major adverse cardiovascular events
timeFrame: At 12 months
measure: Quality of life assessed by the EuroQol-5D (EQ5D) questionnaire
timeFrame: At 12 months
measure: Dosage of inflammation biomarkers
timeFrame: up to 3 months
measure: number of treatment discontinuation
timeFrame: 5 days
measure: number of adverse events
timeFrame: up to 5 days
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Hospitalier Universitaire Angers
city: Bron
country: France
facility: Hôpital Louis Pradel
city: Lyon
country: France
facility: Hôpital Saint Joseph
city: Montpellier
country: France
facility: CHU Arnaud de Villeneuve
city: Mulhouse
country: France
facility: CHU de Mulhouse
city: Poitiers
country: France
facility: CHU de Poitiers
city: Toulouse
country: France
facility: CHU de Rangueil
city: Tours
country: France
facility: CHRU de Tours
Study officials:
affiliation: Hospices Civils de Lyon, Hôpital Louis Pradel, Service de cardiologie, 69677, Bron.
name: Nathan MEWTON, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mewton N, Roubille F, Bresson D, Prieur C, Bouleti C, Bochaton T, Ivanes F, Dubreuil O, Biere L, Hayek A, Derimay F, Akodad M, Alos B, Haider L, El Jonhy N, Daw R, De Bourguignon C, Dhelens C, Finet G, Bonnefoy-Cudraz E, Bidaux G, Boutitie F, Maucort-Boulch D, Croisille P, Rioufol G, Prunier F, Angoulvant D. Effect of Colchicine on Myocardial Injury in Acute Myocardial Infarction. Circulation. 2021 Sep 14;144(11):859-869. doi: 10.1161/CIRCULATIONAHA.121.056177. Epub 2021 Aug 23.