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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 : June 8, 2018
Sponsor:
Information provided by (Responsible Party):
Hospital Universitari Vall d'Hebron Research Institute

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.

Condition or disease Intervention/treatment Phase
ST Elevation Acute Myocardial Infarction Drug: Exenatide Other: Remote Ischemic Conditioning (RIC) Drug: Placebo Phase 3

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 428 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: COMBinAtion Therapy in Myocardial Infarction: The COMBAT-MI Trial
Actual Study Start Date : March 2016
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : November 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack
Drug Information available for: Exenatide

Arm Intervention/treatment
Active Comparator: Remote Ischemic Conditioning
Remote Ischemic Conditioning + placebo
Other: Remote Ischemic Conditioning (RIC)
Remote ischemic conditioning with a cuff in the arm

Drug: Placebo
Intrevenous administration of Placebo

Active Comparator: Combined treatment
Remote Ischemic Conditioning + exenatide
Drug: Exenatide
Intravenous administration of Exenatide

Other: Remote Ischemic Conditioning (RIC)
Remote ischemic conditioning with a cuff in the arm

Placebo Comparator: Placebo
Sham Remote Ischemic Conditioning + placebo
Other: Remote Ischemic Conditioning (RIC)
Remote ischemic conditioning with a cuff in the arm

Drug: Placebo
Intrevenous administration of Placebo

Active Comparator: Exenatide
Sham Remote Ischemic Conditioning + exenatide
Drug: Exenatide
Intravenous administration of Exenatide

Other: Remote Ischemic Conditioning (RIC)
Remote ischemic conditioning with a cuff in the arm




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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 .

  6. 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


Other Outcome Measures:
  1. 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

  2. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02404376


Contacts
Contact: David García-Dorado, MD, PhD, Professor +34932746070 dgdorado@vhebron.net
Contact: David García- Dorado, MD, PhD, Professor +34932746070 dgdorado@vhebron.net

Locations
Spain
Hospital Universitari Germans Trias i Pujol Recruiting
Badalona, Barcelona, Spain, 08916
Contact: Antoni Bayés Genís, MD, PhD    +34 93 497 89 15    abayesgenis@gmail.com   
Principal Investigator: Antoni Bayés- Genís, MD, PhD         
Principal Investigator: Eduard Fernández-Nofrerias, MD         
Hospital Clínico Universitario de Santiago de Compostela Recruiting
Santiago de Compostela, La Coruña, Spain, 15706
Contact: José Ramón González Juanatey, MD, PhD       Jose.Ramon.Gonzalez.Juanatey@sergas.es   
Hospital de la Santa Creu i Sant Pau Not yet recruiting
Barcelona, Spain, 08026
Contact: Joan García Picart, MD       JGarciaPi@santpau.cat   
Hospital Universitario Valle de Hebron Recruiting
Barcelona, Spain, 08035
Contact: Gerad Marti, MD    +34 93 274 6134 ext 6134    drgmarti@googlemail.com   
Contact: Imanol Otaegui, MD    +34 93 274 6155    iotaegui@vhebron.net   
Principal Investigator: David García- Dorado García, MD PhD         
Hospital Universitari de Girona Josep Trueta Not yet recruiting
Girona, Spain, 17007
Contact: Joan Bassaganyas Vilarrasa, MD, PhD       jbassaganyas.girona.ics@gencat.cat   
Hospital Universitario Arnau de Vilanova Recruiting
Lleida, Spain, 25198
Contact: Fernando Worner Diz, MD, PhD       fworner.lleida.ics@gencat.cat   
Hospital Universitario Fundación Jiménez Díaz Recruiting
Madrid, Spain, 28040
Contact: Borja Ibáñez Cabeza, MD, PhD       bibanez@cnic.es   
Hospital Universitari de Tarragona Joan 23 Recruiting
Tarragona, Spain, 43005
Contact: Alfredo Bardají Ruíz, MD, PhD       abardaji.hj23.ics@gencat.cat   
Sponsors and Collaborators
Hospital Universitari Vall d'Hebron Research Institute
Investigators
Principal Investigator: David García-Dorado, MD, PhD, Professor Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca

Publications of Results:
Other Publications:
Responsible Party: Hospital Universitari Vall d'Hebron Research Institute
ClinicalTrials.gov Identifier: NCT02404376     History of Changes
Other Study ID Numbers: COMBAT-MI
First Posted: March 31, 2015    Key Record Dates
Last Update Posted: June 8, 2018
Last Verified: January 2018

Keywords provided by Hospital Universitari Vall d'Hebron Research Institute:
STEMI
Reperfusion Injury
Myocardial Infarction
Myocardial Ischemia
Remote Ischemic Conditioning
Exenatide
Glucagon-Like Peptide-1 (GLP-1)
Acute Coronary Syndrome
Cardioprotection

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists