COlchicine for Left VEntricular Remodeling Treatment in Acute Myocardial Infarction

NCT03156816 | Completed Phase 2 DMC

• 2 other identifiers: 69HCL17_00342017-004090-13
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 8

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.

Conditions

Myocardial Infarction

Keywords

Myocardial Infarction; STEMI; Inflammation; Left ventricular remodeling; Colchicine; CMR

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• LV ejection fraction

  At 5 days

• Microvascular obstruction (in % of LV mass)

  At 5 days

• Absolute adverse left ventricular remodeling (mL)

  at 3 months

• Relative ventricular remodeling (%)

  at 3 months

• Infarct size in % of LV mass

  At 3 months

Study Arms (2)

Colchicine

EXPERIMENTAL

The patients will receive an oral bolus of colchicine of 2 mg followed by 0.5 mg b.i.d. during 5 days.

Drug: Colchicine group (experimental arm)

Control arm

PLACEBO COMPARATOR

The patients will receive an oral bolus of placebo of 2 mg followed by 0.5 mg b.i.d. during 5 days.

Drug: Placebo group (control arm)

Interventions

Colchicine group (experimental arm) DRUG

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.

Colchicine

Placebo group (control arm) DRUG

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.

Control arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (8)

Centre Hospitalier Universitaire Angers

Angers, France

Location

Hôpital Louis Pradel

Bron, 69677, France

Location

Hôpital Saint Joseph

Lyon, France

Location

CHU Arnaud de Villeneuve

Montpellier, France

Location

CHU de Mulhouse

Mulhouse, France

Location

CHU de Poitiers

Poitiers, France

Location

CHU de Rangueil

Toulouse, France

Location

CHRU de Tours

Tours, France

Location

Related Publications (1)

• 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.

  PMID: 34420373 RESULT

MeSH Terms

Conditions

Myocardial Infarction; ST Elevation Myocardial Infarction; Inflammation; Ventricular Remodeling

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Pathological Conditions, Anatomical

Study Officials

• Nathan MEWTON, PhD

  Hospices Civils de Lyon, Hôpital Louis Pradel, Service de cardiologie, 69677, Bron.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 17, 2017
• Study Start: July 23, 2018
• Primary Completion: November 8, 2020
• Study Completion: August 16, 2021
• Last Updated: August 1, 2025

Record last verified: 2022-01

Locations

FR (8)