Epicardial Infarct Repair Using CorMatrix®-ECM: Clinical Feasibility Study
Condition: Acute Coronary Syndrome; Heart Failure
MeSH terms: Acute Coronary Syndrome
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Epicardial Infarct Repair with CorMatrix-Extracellular Matrix (ECM) is an open-label,
      non-randomized, feasibility pilot study. Following ischemic injury the ECM of the heart
      adversely remodels leading to cardiac fibrosis, left ventricular (LV) dilatation and
      subsequent heart failure. Preclinical evidence demonstrates that epicardial infarct repair
      with CorMatrix-ECM restores the damaged ECM, prevents LV dilatation and improves myocardial
      performance. This study will interrogate epicardial infarct repair in patients undergoing
      coronary artery bypass grafting (CABG) surgery within 6 weeks following acute myocardial
      infarction as an adjunct to surgical revascularization. Patients will be evaluated for
      markers of cardiac function and left ventricular remodelling using cardiac magnetic resonance
      imaging (MRI). Adverse events will be monitored to ensure safety.
    

Detailed description: 
      RATIONALE: Following ischemic injury the extracellular matrix (ECM) of the heart adversely
      remodels leading to cardiac fibrosis, left ventricular (LV) dilatation and subsequent heart
      failure. Preclinical evidence suggests that the epicardial application of a healthy biologic
      ECM may reverse the adverse ECM remodeling that takes place following ischemic injury
      preventing LV dilatation and subsequent heart failure. The investigators have demonstrated
      that epicardial infarct repair with CorMatrix-ECM restores the damaged ECM, prevents LV
      dilatation and improves myocardial performance. The investigators believe that epicardial
      infarct repair may not only restrain the infarcted myocardium to prevent infarct expansion
      and LV dilatation, but owing to it's biologic nature, help to provide a healthy ECM
      environment restoring ECM homeostasis and architecture. The investigators therefore propose
      clinical investigation epicardial infarct repair in patients undergoing coronary artery
      bypass grafting (CABG) surgery within 6 weeks following acute myocardial infarction as an
      adjunct to surgical revascularization. This is a patient population commonly referred for
      CABG surgery. While complete surgical revascularization can prevent further ischemic insult
      and salvage stunned or hibernating myocardium, it does not restore function to the infarcted
      myocardium resulting from the acute ischemic injury. The investigator's previous studies
      suggest that epicardial infarct repair as an adjunct to CABG surgery in this patient
      population may help improve myocardial function in this previously untreatable territory.

      STUDY DESIGN: This is an open-label, non-randomized, feasibility pilot study

      PRIMARY OBJECTIVE:

      • To evaluate the feasibility of epicardial infarct repair performed with CorMatrix-ECM as an
      adjunct to CABG surgery in patients undergoing surgery during the subacute period following
      myocardial infarction (MI).

      SECONDARY OBJECTIVES:

        -  To evaluate the feasibility of identifying the infarct area to be treated by epicardial
           infarct repair and measure regional function and tissue characteristics within the
           treated area using cardiac magnetic resonance (CMR) imaging.

        -  To evaluate the safety of epicardial infarct repair performed with CorMatrix-ECM as an
           adjunct to CABG surgery.

      NUMBER OF SUBJECTS: Eight

      TEST PRODUCT, DOSE, AND ROUTE OF ADMINISTRATION: CorMatrix-ECM will be surgically applied to
      the epicardial surface of the anterior LV wall at the time of coronary artery bypass surgery.

      CONTROL PRODUCT, DOSE AND ROUTE OF ADMINISTRATION: No control group will be performed in this
      pilot trial.

      DURATION OF SUBJECT PARTICIPATION AND DURATION OF STUDY: Subjects will be involved in the
      study for up to 6 months.

      Screening/Enrollment: 0-6 weeks between acute coronary syndrome presentation and CABG
      surgery.

      Treatment: Day of CABG surgery. Follow-up: 6 months postoperatively. Total duration of the
      study is expected to be 9 months. Three months for subject enrollment and 6 months for final
      subject follow-up.

      CONCOMMITANT MEDICATIONS:

      Prohibited: Immunosuppressive medications (including steroids). Allowed: Any other
      medications.

      FEASIBILITY EVALUATIONS: Feasibility will be accessed through qualitative evaluation by the
      performing surgeon and successful measurement of cardiac function and tissue characterization
      by CMR.

      PRIMARY ENDPOINT:

      • Feasibility of epicardial infarct repair performed with CorMatrix-ECM as an adjunct to CABG
      surgery in patients undergoing surgery during the subacute period following myocardial
      infarction (MI) evaluated by the performing surgeon though qualitative observation.

      SECONDARY ENDPOINTS:

        -  Feasibility of measuring regional myocardial function and tissue characteristics within
           the treated area using cardiac magnetic resonance (CMR) imaging.

        -  The safety of epicardial infarct repair performed with CorMatrix-ECM.

      SAFETY EVALUATIONS :

      Adverse events including: all cause mortality; cardiovascular mortality; MACCE; major
      bleeding events; primary surgical site infection; and myocardial constriction will be
      recorded.

      RATIONALE FOR NUMBER OF STUDY SUBJECTS: This is a pilot study designed to access the
      feasibility of performing epicardial infarct repair with CorMatrix-ECM in subacute MI
      patients going for CABG surgery, the feasibility of measuring cardiac function and various
      tissue characteristics within the treated myocardium by CMR in this patient population, and
      the safety of epicardial infarct repair performed at the time of CABG surgery. Given the
      preliminary nature of this study 8 subjects will be tested to confirm feasibility and inform
      future randomized control trial study design.
    

Intervention name(s): Epicardial Infarct Repair with CorMatrix-ECM; Coronary Artery Bypass Grafting Surgery
Intervention type(s): Device; Procedure
Intervention description(s): CorMatrix-ECM-biomaterial will be surgically applied to the epicardial surface of the infarct myocardium at the time of coronary artery bypass surgery; All participants will undergo standard coronary artery bypass grafting surgery to treat coronary artery disease
Other intervention name(s): SIS-ECM (small intestine submucosa extracellular matrix); Aorto-coronary bypass surgery
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment