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CompletedNCT03156816COVERT-MIUpdated Aug 1, 2025

COlchicine for Left VEntricular Remodeling Treatment in Acute Myocardial Infarction

A Phase 2 interventional study of Colchicine group (experimental arm) and Placebo group (control arm) in Myocardial Infarction, sponsored by Hospices Civils de Lyon. Completed at 8 sites in France. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2025-08-01.

Sponsored by Hospices Civils de Lyon · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
194
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Myocardial Infarction

Keywords

  • Myocardial Infarction
  • STEMI
  • Inflammation
  • Left ventricular remodeling
  • Colchicine
  • CMR
03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
194 participants (actual)

Study arms

  • Experimental
    Colchicine

    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)

  • Placebo comparator
    Control arm

    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

  • DrugColchicine 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.

  • DrugPlacebo 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.

05

What researchers measure

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

    Time frame: 5 days

Secondary outcomes

  1. LV ejection fraction

    Time frame: At 5 days

  2. Microvascular obstruction (in % of LV mass)

    Time frame: At 5 days

  3. Absolute adverse left ventricular remodeling (mL)

    Time frame: at 3 months

  4. Relative ventricular remodeling (%)

    Time frame: at 3 months

  5. Infarct size in % of LV mass

    Infarct size in % of LV mass assessed by ce-CMR

    Time frame: At 3 months

  6. LVEDV

    LVEDV (indexed to body surface area) as determined by CMR at the acute phase and 3 months follow-up respectively

    Time frame: At 3 months

  7. LVESV

    LVEDV (indexed to body surface area) as determined by CMR at the acute phase and 3 months follow-up respectively

    Time frame: at 3 months

  8. Relative LV ejection fraction

    Time frame: 5 days

  9. Percent of thrombi in the LV

    Time frame: At 5 days

  10. 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.

    Time frame: at 3 months

  11. 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.

    Time frame: At 12 months

  12. 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).

    Time frame: At 12 months

  13. 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 1β and interleukin 18, complement system components.

    Time frame: up to 3 months

  14. number of treatment discontinuation

    Time frame: 5 days

  15. number of adverse events

    (diarrhea, nausea/vomiting and myelotoxicity, renal function at 48H).

    Time frame: up to 5 days

06

Study locations

8 sites
  • Centre Hospitalier Universitaire Angers
    Angers, France
  • Hôpital Louis Pradel
    Bron, 69677, 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, France
07

References and documents

Publications

  • 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. PubMed 34420373 ↗
08

Registry details

Key details

Study ID
NCT03156816
Lead sponsor
Hospices Civils de Lyon
Responsible party
Sponsor
First posted
May 17, 2017
Start date
Jul 23, 2018
Primary completion
Nov 8, 2020
Completion
Aug 16, 2021
Last update
Aug 1, 2025

Study contacts

Nathan MEWTON, PhD
principal investigator · Hospices Civils de Lyon, Hôpital Louis Pradel, Service de cardiologie, 69677, Bron.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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