COMBinAtion Therapy in Myocardial Infarction: The COMBAT-MI Trial

Vall d'Hebron University Hospital (HUVH)

Status and phase: Completed; Phase 3

Conditions: ST Elevation Acute Myocardial Infarction

Treatments: Drug: Exenatide; Drug: Placebo; Other: Remote Ischemic Conditioning (RIC)

Study type: Interventional

Funder types: Other

Identifiers

NCT02404376

COMBAT-MI

Details and patient eligibility

About

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.

Full 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.

Enrollment: 378 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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378 participants in 4 patient groups, including a placebo group

Remote Ischemic Conditioning

Active Comparator group

Description:

Remote Ischemic Conditioning + placebo

Treatment:

Drug: Placebo

Other: Remote Ischemic Conditioning (RIC)

Combined treatment

Active Comparator group

Description:

Remote Ischemic Conditioning + exenatide

Treatment:

Drug: Exenatide

Other: Remote Ischemic Conditioning (RIC)

Placebo

Placebo Comparator group

Description:

Sham Remote Ischemic Conditioning + placebo

Treatment:

Drug: Placebo

Other: Remote Ischemic Conditioning (RIC)

Exenatide

Active Comparator group

Description:

Sham Remote Ischemic Conditioning + exenatide

Treatment:

Drug: Exenatide

Other: Remote Ischemic Conditioning (RIC)