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COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction (COLD-MI)

Primary Purpose

Myocardial Infarction, Acute

Status
Terminated
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Colchicine
Sponsored by
University Hospital, Montpellier
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Myocardial Infarction, Acute focused on measuring Myocardial infarction, Sympathetic denervation, Heart failure

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UH Montpellier

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Colchicine

Comparator

Arm Description

colchicine and standard therapy

standard therapy

Outcomes

Primary Outcome Measures

Percentage of myocardial denervation
assess by MIBG (méta-iodobenzylguanidine)-nuclear cardiac imaging

Secondary Outcome Measures

Change in the heart-to-mediastinum ratio
The heart-to-mediastinum (H/M) ratio, the heart count normalized for the mediastinum count, is used as a quantitative index in cardiac 123 I-MIBG imaging.
Left Ventricular Ejection Fraction in percent
By transthoracic echocardiogram (TTE)
Left Ventricular Ejection Fraction in percent
By MIBG (méta-iodobenzylguanidine)-nuclear cardiac imaging
Left Ventricular Ejection Fraction in percent
By transthoracic echocardiogram (TTE)
Change in Sinus variability
by 24 hours holter recording : SDNN (Standard Deviation of NN intervals) will be measured
Change in Sinus variability
by 24 hours holter recording : SDNN (Standard Deviation of NN intervals) will be measured
Basic ECG parameters (QRS duration)
Basic ECG parameters (QRS duration)
Basic ECG parameters (corrected QT)
Basic ECG parameters (corrected QT)
Number of ventricular extrasystole (2 or 3 VES) per 24 hours on the Holter
Number of bursts (2 or 3 VES) per 24 hours on the Holter
Number of bursts (2 or 3 VES) per 24 hours on the Holter
Number of ventricular or supraventricular tachycardia (>3 VES) episodes per 24 hours
Number of ventricular or supraventricular tachycardia (>3 VES) episodes per 24 hours
Time from randomization to death (total mortality)
Time from randomization to heart failure hospitalization
Time from randomization to all-cause hospitalization
Variations in the levels of neurotrophic molecular markers
Concentration of NGF ng/mL
Variations in the levels of neurotrophic molecular markers
Concentration of NGF ng/mL
Variations in the levels of neurotrophic molecular markers
Concentration of proNGF ng/mL
Variations in the levels of neurotrophic molecular markers
Concentration of proNGF ng/mL
Variations in the levels of neurotrophic molecular markers
Concentration of BDNF ng/mL
Variations in the levels of neurotrophic molecular markers
Concentration of BDNF ng/mL
Biological evaluation of infarction size Creatine PhosphoKinase (CPK)
Area Under Curve (AUC) of CPK
Biological evaluation of infarction size (troponin)
Area Under Curve (AUC) of Troponin
Post infarction systemic inflammation evaluation
Concentration of biomarkers from blood : CRP (mg/L)
Post infarction systemic inflammation evaluation
Concentration of biomarkers from blood : CRP (mg/L)
Post infarction systemic inflammation evaluation
Concentration of biomarkers from blood : sST2 (ng/mL)
Post infarction systemic inflammation evaluation
Concentration of biomarkers from blood : sST2 (ng/mL)
Infarct size in percentage of left ventricular
Number of Adverse event
Comparison of adverse events between 2 arms

Full Information

First Posted
April 29, 2020
Last Updated
December 14, 2022
Sponsor
University Hospital, Montpellier
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1. Study Identification

Unique Protocol Identification Number
NCT04420624
Brief Title
COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction
Acronym
COLD-MI
Official Title
COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Terminated
Why Stopped
Inclusion period completed
Study Start Date
December 4, 2020 (Actual)
Primary Completion Date
May 24, 2022 (Actual)
Study Completion Date
May 24, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Montpellier

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Infarction, Acute
Keywords
Myocardial infarction, Sympathetic denervation, Heart failure

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Prospective, phase IIb, monocentric, randomized, open labeled with 2 parallel study arms.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Colchicine
Arm Type
Experimental
Arm Description
colchicine and standard therapy
Arm Title
Comparator
Arm Type
No Intervention
Arm Description
standard therapy
Intervention Type
Drug
Intervention Name(s)
Colchicine
Other Intervention Name(s)
no other name
Intervention Description
1 mg (or 0.5mg) tablet of colchicine taken once a day for 1 month
Primary Outcome Measure Information:
Title
Percentage of myocardial denervation
Description
assess by MIBG (méta-iodobenzylguanidine)-nuclear cardiac imaging
Time Frame
6 month
Secondary Outcome Measure Information:
Title
Change in the heart-to-mediastinum ratio
Description
The heart-to-mediastinum (H/M) ratio, the heart count normalized for the mediastinum count, is used as a quantitative index in cardiac 123 I-MIBG imaging.
Time Frame
6 month
Title
Left Ventricular Ejection Fraction in percent
Description
By transthoracic echocardiogram (TTE)
Time Frame
6 month
Title
Left Ventricular Ejection Fraction in percent
Description
By MIBG (méta-iodobenzylguanidine)-nuclear cardiac imaging
Time Frame
6 month
Title
Left Ventricular Ejection Fraction in percent
Description
By transthoracic echocardiogram (TTE)
Time Frame
1 month
Title
Change in Sinus variability
Description
by 24 hours holter recording : SDNN (Standard Deviation of NN intervals) will be measured
Time Frame
6 month
Title
Change in Sinus variability
Description
by 24 hours holter recording : SDNN (Standard Deviation of NN intervals) will be measured
Time Frame
1 month
Title
Basic ECG parameters (QRS duration)
Time Frame
6 month
Title
Basic ECG parameters (QRS duration)
Time Frame
1 month
Title
Basic ECG parameters (corrected QT)
Time Frame
1 month
Title
Basic ECG parameters (corrected QT)
Time Frame
6 month
Title
Number of ventricular extrasystole (2 or 3 VES) per 24 hours on the Holter
Time Frame
6 month
Title
Number of bursts (2 or 3 VES) per 24 hours on the Holter
Time Frame
1 month
Title
Number of bursts (2 or 3 VES) per 24 hours on the Holter
Time Frame
6 month
Title
Number of ventricular or supraventricular tachycardia (>3 VES) episodes per 24 hours
Time Frame
1 month
Title
Number of ventricular or supraventricular tachycardia (>3 VES) episodes per 24 hours
Time Frame
6 month
Title
Time from randomization to death (total mortality)
Time Frame
6 month
Title
Time from randomization to heart failure hospitalization
Time Frame
6 month
Title
Time from randomization to all-cause hospitalization
Time Frame
6 month
Title
Variations in the levels of neurotrophic molecular markers
Description
Concentration of NGF ng/mL
Time Frame
Between hospitalization and 1 month
Title
Variations in the levels of neurotrophic molecular markers
Description
Concentration of NGF ng/mL
Time Frame
Between 1 month and 6 months
Title
Variations in the levels of neurotrophic molecular markers
Description
Concentration of proNGF ng/mL
Time Frame
Between hospitalization and 1 month
Title
Variations in the levels of neurotrophic molecular markers
Description
Concentration of proNGF ng/mL
Time Frame
Between 1 month and 6 months
Title
Variations in the levels of neurotrophic molecular markers
Description
Concentration of BDNF ng/mL
Time Frame
Between hospitalization and 1 month
Title
Variations in the levels of neurotrophic molecular markers
Description
Concentration of BDNF ng/mL
Time Frame
Between 1 month and 6 months
Title
Biological evaluation of infarction size Creatine PhosphoKinase (CPK)
Description
Area Under Curve (AUC) of CPK
Time Frame
During hospitalization (Day 1 to Day 5)
Title
Biological evaluation of infarction size (troponin)
Description
Area Under Curve (AUC) of Troponin
Time Frame
During hospitalization (Day 1 to Day 5)
Title
Post infarction systemic inflammation evaluation
Description
Concentration of biomarkers from blood : CRP (mg/L)
Time Frame
Between hospitalization and 1 month
Title
Post infarction systemic inflammation evaluation
Description
Concentration of biomarkers from blood : CRP (mg/L)
Time Frame
Between 1 month and 6 months
Title
Post infarction systemic inflammation evaluation
Description
Concentration of biomarkers from blood : sST2 (ng/mL)
Time Frame
Between hospitalization and 1 month
Title
Post infarction systemic inflammation evaluation
Description
Concentration of biomarkers from blood : sST2 (ng/mL)
Time Frame
Between 1 month and 6 months
Title
Infarct size in percentage of left ventricular
Time Frame
6 month
Title
Number of Adverse event
Description
Comparison of adverse events between 2 arms
Time Frame
from randomization to 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
UH Montpellier
City
Montpellier
ZIP/Postal Code
34090
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction

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