<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04420624</url>
  </required_header>
  <id_info>
    <org_study_id>7727</org_study_id>
    <nct_id>NCT04420624</nct_id>
  </id_info>
  <brief_title>COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction</brief_title>
  <acronym>COLD-MI</acronym>
  <official_title>COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Montpellier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Montpellier</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the benefit of colchicine on induced denervation after myocardial&#xD;
      infarction. Patients who have suffered a documented De Novo myocardial infarction and&#xD;
      completed a revascularization procedure will receive either colchicine on top of standard&#xD;
      therapy, compared to standard therapy alone (1:1 allocation ratio). Colchicine 1mg (or 0.5mg)&#xD;
      will be initiated within 48h after percutaneous revascularization and prescribed for one&#xD;
      month.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      COLD-MI study aims to explore colchicine's impact on myocardial denervation following&#xD;
      reperfused acute myocardial infarction. Acute myocardial infarction is the leading cause of&#xD;
      heart failure (HF). It induces myocardial denervation predisposing to ventricular rhythm&#xD;
      disorders and death. This denervation linked to infarction's size occurs by direct ischaemic&#xD;
      mechanisms during the initial coronary occlusion (initially non-vascularised zone) and&#xD;
      secondarily by cardiac remodelling in the context of the heart failure (HF). In usual&#xD;
      practice, cardiac denervation which intensity is correlated with rhythm and mortality risks,&#xD;
      can be evaluated by scintigraphy. In a murine reperfusion model of ischemia, the direct&#xD;
      anti-inflammatory effect of colchicine reduces the size of the necrosis and improves&#xD;
      post-ischemic remodeling. This suggests that colchicine may reduce myocardial denervation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Inclusion period completed&#xD;
  </why_stopped>
  <start_date type="Actual">December 4, 2020</start_date>
  <completion_date type="Actual">May 24, 2022</completion_date>
  <primary_completion_date type="Actual">May 24, 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Prospective, phase IIb, monocentric, randomized, open labeled with 2 parallel study arms.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of myocardial denervation</measure>
    <time_frame>6 month</time_frame>
    <description>assess by MIBG (méta-iodobenzylguanidine)-nuclear cardiac imaging</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the heart-to-mediastinum ratio</measure>
    <time_frame>6 month</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left Ventricular Ejection Fraction in percent</measure>
    <time_frame>6 month</time_frame>
    <description>By transthoracic echocardiogram (TTE)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left Ventricular Ejection Fraction in percent</measure>
    <time_frame>6 month</time_frame>
    <description>By MIBG (méta-iodobenzylguanidine)-nuclear cardiac imaging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left Ventricular Ejection Fraction in percent</measure>
    <time_frame>1 month</time_frame>
    <description>By transthoracic echocardiogram (TTE)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Sinus variability</measure>
    <time_frame>6 month</time_frame>
    <description>by 24 hours holter recording : SDNN (Standard Deviation of NN intervals) will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Sinus variability</measure>
    <time_frame>1 month</time_frame>
    <description>by 24 hours holter recording : SDNN (Standard Deviation of NN intervals) will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Basic ECG parameters (QRS duration)</measure>
    <time_frame>6 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Basic ECG parameters (QRS duration)</measure>
    <time_frame>1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Basic ECG parameters (corrected QT)</measure>
    <time_frame>1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Basic ECG parameters (corrected QT)</measure>
    <time_frame>6 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of ventricular extrasystole (2 or 3 VES) per 24 hours on the Holter</measure>
    <time_frame>6 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of bursts (2 or 3 VES) per 24 hours on the Holter</measure>
    <time_frame>1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of bursts (2 or 3 VES) per 24 hours on the Holter</measure>
    <time_frame>6 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of ventricular or supraventricular tachycardia (&gt;3 VES) episodes per 24 hours</measure>
    <time_frame>1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of ventricular or supraventricular tachycardia (&gt;3 VES) episodes per 24 hours</measure>
    <time_frame>6 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from randomization to death (total mortality)</measure>
    <time_frame>6 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from randomization to heart failure hospitalization</measure>
    <time_frame>6 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from randomization to all-cause hospitalization</measure>
    <time_frame>6 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variations in the levels of neurotrophic molecular markers</measure>
    <time_frame>Between hospitalization and 1 month</time_frame>
    <description>Concentration of NGF ng/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variations in the levels of neurotrophic molecular markers</measure>
    <time_frame>Between 1 month and 6 months</time_frame>
    <description>Concentration of NGF ng/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variations in the levels of neurotrophic molecular markers</measure>
    <time_frame>Between hospitalization and 1 month</time_frame>
    <description>Concentration of proNGF ng/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variations in the levels of neurotrophic molecular markers</measure>
    <time_frame>Between 1 month and 6 months</time_frame>
    <description>Concentration of proNGF ng/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variations in the levels of neurotrophic molecular markers</measure>
    <time_frame>Between hospitalization and 1 month</time_frame>
    <description>Concentration of BDNF ng/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variations in the levels of neurotrophic molecular markers</measure>
    <time_frame>Between 1 month and 6 months</time_frame>
    <description>Concentration of BDNF ng/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biological evaluation of infarction size Creatine PhosphoKinase (CPK)</measure>
    <time_frame>During hospitalization (Day 1 to Day 5)</time_frame>
    <description>Area Under Curve (AUC) of CPK</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biological evaluation of infarction size (troponin)</measure>
    <time_frame>During hospitalization (Day 1 to Day 5)</time_frame>
    <description>Area Under Curve (AUC) of Troponin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post infarction systemic inflammation evaluation</measure>
    <time_frame>Between hospitalization and 1 month</time_frame>
    <description>Concentration of biomarkers from blood : CRP (mg/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post infarction systemic inflammation evaluation</measure>
    <time_frame>Between 1 month and 6 months</time_frame>
    <description>Concentration of biomarkers from blood : CRP (mg/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post infarction systemic inflammation evaluation</measure>
    <time_frame>Between hospitalization and 1 month</time_frame>
    <description>Concentration of biomarkers from blood : sST2 (ng/mL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post infarction systemic inflammation evaluation</measure>
    <time_frame>Between 1 month and 6 months</time_frame>
    <description>Concentration of biomarkers from blood : sST2 (ng/mL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infarct size in percentage of left ventricular</measure>
    <time_frame>6 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Adverse event</measure>
    <time_frame>from randomization to 6 months</time_frame>
    <description>Comparison of adverse events between 2 arms</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Myocardial Infarction, Acute</condition>
  <arm_group>
    <arm_group_label>Colchicine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>colchicine and standard therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comparator</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>standard therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Colchicine</intervention_name>
    <description>1 mg (or 0.5mg) tablet of colchicine taken once a day for 1 month</description>
    <arm_group_label>Colchicine</arm_group_label>
    <other_name>no other name</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age from 18 to 80 year old&#xD;
&#xD;
          -  Hospitalization within 12 hours of onset of acute chest pain&#xD;
&#xD;
          -  Patient must have suffered a documented acute myocardial infarction&#xD;
&#xD;
          -  Coronary occlusion on initial angiography (culprit artery with aTIMI (Thrombolysis in&#xD;
             Myocardial Infarction) flow 1 or 0)&#xD;
&#xD;
          -  Patient eligible for a revascularization procedure by PTCA (Percutaneous transluminal&#xD;
             coronary angioplasty)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a history of myocardial infarction prior to the current episode&#xD;
&#xD;
          -  Patient in cardiogenic shock or with hemodynamic instability&#xD;
&#xD;
          -  Patients with severe hepatic or renal dysfunction (GFR ≤30 mL/min)&#xD;
&#xD;
          -  Pregnant women or women of childbearing age without contraception&#xD;
&#xD;
          -  Treatment with a potent CYP3A4 inhibitor or a P-glycoprotein inhibitor in patients&#xD;
             with renal or hepatic impairement&#xD;
&#xD;
          -  Association with macrolides (except spiramycin)&#xD;
&#xD;
          -  Association with pristinamycin&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UH Montpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34090</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>April 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>December 14, 2022</last_update_submitted>
  <last_update_submitted_qc>December 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Myocardial infarction</keyword>
  <keyword>Sympathetic denervation</keyword>
  <keyword>Heart failure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>Infarction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colchicine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04420624
org study id: 7727
nct id: NCT04420624
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective, phase IIb, monocentric, randomized, open labeled with 2 parallel study arms.
primary purpose: Prevention
masking: None (Open Label)
measure: Percentage of myocardial denervation
time frame: 6 month
description: assess by MIBG (méta-iodobenzylguanidine)-nuclear cardiac imaging
measure: Change in the heart-to-mediastinum ratio
time frame: 6 month
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.
measure: Left Ventricular Ejection Fraction in percent
time frame: 6 month
description: By transthoracic echocardiogram (TTE)
measure: Left Ventricular Ejection Fraction in percent
time frame: 6 month
description: By MIBG (méta-iodobenzylguanidine)-nuclear cardiac imaging
measure: Left Ventricular Ejection Fraction in percent
time frame: 1 month
description: By transthoracic echocardiogram (TTE)
measure: Change in Sinus variability
time frame: 6 month
description: by 24 hours holter recording : SDNN (Standard Deviation of NN intervals) will be measured
measure: Change in Sinus variability
time frame: 1 month
description: by 24 hours holter recording : SDNN (Standard Deviation of NN intervals) will be measured
measure: Basic ECG parameters (QRS duration)
time frame: 6 month
measure: Basic ECG parameters (QRS duration)
time frame: 1 month
measure: Basic ECG parameters (corrected QT)
time frame: 1 month
measure: Basic ECG parameters (corrected QT)
time frame: 6 month
measure: Number of ventricular extrasystole (2 or 3 VES) per 24 hours on the Holter
time frame: 6 month
measure: Number of bursts (2 or 3 VES) per 24 hours on the Holter
time frame: 1 month
measure: Number of bursts (2 or 3 VES) per 24 hours on the Holter
time frame: 6 month
measure: Number of ventricular or supraventricular tachycardia (>3 VES) episodes per 24 hours
time frame: 1 month
measure: Number of ventricular or supraventricular tachycardia (>3 VES) episodes per 24 hours
time frame: 6 month
measure: Time from randomization to death (total mortality)
time frame: 6 month
measure: Time from randomization to heart failure hospitalization
time frame: 6 month
measure: Time from randomization to all-cause hospitalization
time frame: 6 month
measure: Variations in the levels of neurotrophic molecular markers
time frame: Between hospitalization and 1 month
description: Concentration of NGF ng/mL
measure: Variations in the levels of neurotrophic molecular markers
time frame: Between 1 month and 6 months
description: Concentration of NGF ng/mL
measure: Variations in the levels of neurotrophic molecular markers
time frame: Between hospitalization and 1 month
description: Concentration of proNGF ng/mL
measure: Variations in the levels of neurotrophic molecular markers
time frame: Between 1 month and 6 months
description: Concentration of proNGF ng/mL
measure: Variations in the levels of neurotrophic molecular markers
time frame: Between hospitalization and 1 month
description: Concentration of BDNF ng/mL
measure: Variations in the levels of neurotrophic molecular markers
time frame: Between 1 month and 6 months
description: Concentration of BDNF ng/mL
measure: Biological evaluation of infarction size Creatine PhosphoKinase (CPK)
time frame: During hospitalization (Day 1 to Day 5)
description: Area Under Curve (AUC) of CPK
measure: Biological evaluation of infarction size (troponin)
time frame: During hospitalization (Day 1 to Day 5)
description: Area Under Curve (AUC) of Troponin
measure: Post infarction systemic inflammation evaluation
time frame: Between hospitalization and 1 month
description: Concentration of biomarkers from blood : CRP (mg/L)
measure: Post infarction systemic inflammation evaluation
time frame: Between 1 month and 6 months
description: Concentration of biomarkers from blood : CRP (mg/L)
measure: Post infarction systemic inflammation evaluation
time frame: Between hospitalization and 1 month
description: Concentration of biomarkers from blood : sST2 (ng/mL)
measure: Post infarction systemic inflammation evaluation
time frame: Between 1 month and 6 months
description: Concentration of biomarkers from blood : sST2 (ng/mL)
measure: Infarct size in percentage of left ventricular
time frame: 6 month
measure: Number of Adverse event
time frame: from randomization to 6 months
description: Comparison of adverse events between 2 arms
arm group label: Colchicine
arm group type: Experimental
description: colchicine and standard therapy
arm group label: Comparator
arm group type: No Intervention
description: standard therapy
intervention type: Drug
intervention name: Colchicine
description: 1 mg (or 0.5mg) tablet of colchicine taken once a day for 1 month
arm group label: Colchicine
other name: no other name
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: France
responsible party type: Sponsor
mesh term: Myocardial Infarction
mesh term: Infarction
mesh term: Colchicine
sharing ipd: No