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COMBinAtion Therapy in Myocardial Infarction: The COMBAT-MI Trial (COMBAT-MI)

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ClinicalTrials.gov Identifier: NCT02404376
Recruitment Status : Recruiting
First Posted : March 31, 2015
Last Update Posted : April 9, 2019
Sponsor:
Information provided by (Responsible Party):
Hospital Universitari Vall d'Hebron Research Institute

Tracking Information
First Submitted Date  ICMJE March 20, 2015
First Posted Date  ICMJE March 31, 2015
Last Update Posted Date April 9, 2019
Actual Study Start Date  ICMJE March 2016
Estimated Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 1, 2017)
Myocardial Infarct Size [ Time Frame: 3-7 days after pPCI ]
MI, measured by late gadolinium enhancement in CMRI 3-7 days after pPCI, and expressed as percent of left ventricular mass.
Original Primary Outcome Measures  ICMJE
 (submitted: March 26, 2015)
Myocardial Infarct Size [ Time Frame: 2-7 days after pPCI ]
MI, measured by late gadolinium enhancement in CMRI 2-7 days after pPCI, and expressed as percent of left ventricular mass.
Change History Complete list of historical versions of study NCT02404376 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2017)
  • Myocardial salvage index [ Time Frame: 3-7 days after pPCI ]
    Myocardial salvage index defined as the difference between infarct size and area at risk, defined by the T2 CMRI and expressed as a percent of total LV (Left Ventricular) mass, divided by the area at risk.
  • Transmurality index [ Time Frame: 3-7 days after pPCI ]
    Transmurality index, defined as the ratio of the mass of myocardium showing late gadolinium enhancement to the mass of the myocardial segment containing it.
  • Ventricular volumes [ Time Frame: 3-7 days after pPCI ]
    LV (Left Ventricular) end-diastolic volume and LVEF (Left Ventricular Ejection Fraction), as determined by CMRI.
  • Microvascular obstruction [ Time Frame: 3-7 days after pPCI ]
    Volume of myocardium with microvascular obstruction determined by late gadolinium enhancement expressed as percent of infarct size.
  • Markers of successful reperfusion [ Time Frame: First 90 min after reperfusion ]
    Markers of successful myocardial reperfusion: ST segment resolution 90 minutes post-pPCI , TIMI flow and frame-count post-pPCI , and TIMI blush grade .
  • Major adverse cardiac events (MACE) [ Time Frame: Hospital discharge and expected average of 1 week, one year follow-up ]
    MACE rate during hospitalization, defined as death, non-fatal myocardial rupture, or appearance or worsening of heart failure during the hospitalization period and after 1 year of follow-up
Original Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2015)
  • Myocardial salvage index [ Time Frame: 2-7 days after pPCI ]
    Myocardial salvage index defined as the difference between infarct size and area at risk, defined by the T2 CMRI and expressed as a percent of total LV (Left Ventricular) mass, divided by the area at risk.
  • Transmurality index [ Time Frame: 2-7 days after pPCI ]
    Transmurality index, defined as the ratio of the mass of myocardium showing late gadolinium enhancement to the mass of the myocardial segment containing it.
  • Ventricular volumes [ Time Frame: 2-7 days after pPCI ]
    LV (Left Ventricular) end-diastolic volume and LVEF (Left Ventricular Ejection Fraction), as determined by CMRI.
  • Microvascular obstruction [ Time Frame: 2-7 days after pPCI ]
    Volume of myocardium with microvascular obstruction determined by late gadolinium enhancement expressed as percent of infarct size.
  • Markers of successful reperfusion [ Time Frame: First 90 min after reperfusion ]
    Markers of successful myocardial reperfusion: ST segment resolution 90 minutes post-pPCI , TIMI flow and frame-count post-pPCI , and TIMI blush grade .
  • Major adverse cardiac events (MACE) [ Time Frame: Hospital discharge and expected average of 1 week, one year follow-up ]
    MACE rate during hospitalization, defined as death, non-fatal myocardial rupture, or appearance or worsening of heart failure during the hospitalization period and after 1 year of follow-up
Current Other Pre-specified Outcome Measures
 (submitted: May 22, 2017)
  • Substudy: Biomarker analysis in Hospital Universitari Vall d'Hebron Biobank (HUVH Biobank) [ Time Frame: pre- pPCI ]
    To find biomarkers of increased myocardial susceptibility to reperfusion injury in blood samples obtained before PCI
  • PRESPECIFIED SUBGROUP ANALYSIS ACCORDING TO TOTAL ISCHEMIC TIME [ Time Frame: 3-7 days after pPCI ]
    The effects of treatments will be analysed in the subgroup of patients with a total ischemic time of less than 3 hours and of 3 hours of longer.
Original Other Pre-specified Outcome Measures
 (submitted: March 26, 2015)
  • Substudy: Biomarker analysis [ Time Frame: pre- pPCI ]
    To find biomarkers of increased myocardial susceptibility to reperfusion injury in blood samples obtained before PCI
  • PRESPECIFIED SUBGROUP ANALYSIS ACCORDING TO TOTAL ISCHEMIC TIME [ Time Frame: 2-7 days after pPCI ]
    The effects of treatments will be analysed in the subgroup of patients with a total ischemic time of less than 3 hours and of 3 hours of longer.
 
Descriptive Information
Brief Title  ICMJE COMBinAtion Therapy in Myocardial Infarction: The COMBAT-MI Trial
Official Title  ICMJE COMBinAtion Therapy in Myocardial Infarction: The COMBAT-MI Trial
Brief Summary Remote ischemic conditioning (RIC) and intravenous exenatide administered immediately before primary angioplasty have been found to limit infarct size in patients with STEMI (ST segment elevation myocardial infarction), but the reduction is limited. This study investigates whether a combination therapy including both therapies is more effective.
Detailed Description COMBAT-MI is an investigator-driven, randomized, double-blind and placebo-controlled clinical trial aimed at evaluating the effect of Remote Ischemic Conditioning and exenatide, alone and in combination, on Myocardial Infarct size in 428 STEMI patients (107 per group) (ST segment elevation myocardial infarction). Patients with TIMI (Thrombolysis in Myocardial Infarction) flow grade > 1 will be excluded. The study has a 2 x 2 factorial design (Remote Ischemic Conditioning , Exenatide, both or neither). The primary end-point will be Myocardial Infarct size measured by Cardiac Magnetic Resonance Imaging (CMRI) performed 3 - 7 days after primary Percutaneous Coronary Intervention (pPCI) (expressed as % of left ventricular (LV) mass). Sample size has been calculated in 274 patients with TIMI 0-1 available for analysis of the primary end-point, and inclusion will end when this number is reached, which will require, according to the current rate of TIMI 0-1 in our STEMI population, to randomize 428 patients. Secondary end-points will include myocardial salvage index, based on angiographic and CMRI derived estimations of the area at risk, and frequency of Major Adverse Cardiovascular Events (MACE) and of major adverse events during admission.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE ST Elevation Acute Myocardial Infarction
Intervention  ICMJE
  • Drug: Exenatide
    Intravenous administration of Exenatide
  • Other: Remote Ischemic Conditioning (RIC)
    Remote ischemic conditioning with a cuff in the arm
  • Drug: Placebo
    Intrevenous administration of Placebo
Study Arms  ICMJE
  • Active Comparator: Remote Ischemic Conditioning
    Remote Ischemic Conditioning + placebo
    Interventions:
    • Other: Remote Ischemic Conditioning (RIC)
    • Drug: Placebo
  • Active Comparator: Combined treatment
    Remote Ischemic Conditioning + exenatide
    Interventions:
    • Drug: Exenatide
    • Other: Remote Ischemic Conditioning (RIC)
  • Placebo Comparator: Placebo
    Sham Remote Ischemic Conditioning + placebo
    Interventions:
    • Other: Remote Ischemic Conditioning (RIC)
    • Drug: Placebo
  • Active Comparator: Exenatide
    Sham Remote Ischemic Conditioning + exenatide
    Interventions:
    • Drug: Exenatide
    • Other: Remote Ischemic Conditioning (RIC)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 7, 2018)
428
Original Estimated Enrollment  ICMJE
 (submitted: March 26, 2015)
360
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Men or women ≥18 years of age
  • STEMI characterized by 2 mm ST segment elevation in 2 or more V1 through V4 leads or presumed new left bundle branch block with minimum of 1 mm concordant ST elevation or 1 mV(millivolt) ST segment elevation in the limb leads (II, III and aVF leads, I, aVL leads) and V4-V6.
  • Patients presenting within 6 hours of chest pain.

Exclusion Criteria:

  • Known hypersensitivity to exenatide or any of the excipients
  • Known contraindication to CMR imaging such as significant claustrophobia, severe allergy to gadolinium chelate contrast, severe renal insufficiency (defined as estimated glomerular filtration rate [eGFR] (epidermal growth factor receptor) <30 mL/min/1.73 m2), presence of CMRI contraindicated implanted devices (e.g., pacemaker, implanted cardiac defibrillator, cardiac resynchronization therapy device, cochlear implant), embedded metal objects (e.g., shrapnel), or any other contraindication for CMRI.
  • Assumed life expectancy < 1 year e.g. due to non-cardiac disease.
  • TIMI flow grade > 1 at the time of diagnostic coronary angiography. These patients will be excluded from the analysis of infarct size but will be included in the safety analysis.
  • Pregnant women
  • Patients with loss of consciousness or confused, not able to read the information and to sign the writting consent
  • Patients with oro-tracheal intubation
  • Patients with cardiogenic shock persisting 48h after reperfusion
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: David García-Dorado, MD, PhD, Professor +34932746070 dgdorado@vhebron.net
Contact: David García- Dorado, MD, PhD, Professor +34932746070 dgdorado@vhebron.net
Listed Location Countries  ICMJE Spain
Removed Location Countries France,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT02404376
Other Study ID Numbers  ICMJE COMBAT-MI
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hospital Universitari Vall d'Hebron Research Institute
Study Sponsor  ICMJE Hospital Universitari Vall d'Hebron Research Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: David García-Dorado, MD, PhD, Professor Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca
PRS Account Hospital Universitari Vall d'Hebron Research Institute
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP