Pericardial Matrix With Mesenchymal Stem Cells for the Treatment of Patients With Infarcted Myocardial Tissue

Study Overview
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Brief Summary
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Myocardial infarction causes necrosis of myocardial cells and reduces cardiac function. Today, there are treatments such as primary angioplasty and thrombolysis that are effective in limiting cell death after acute myocardial infarction. However, the post-infarct scar often conditions a global ventricular remodeling that can evolve clinically towards heart failure and in more advanced stages the only therapy that completely restores cardiac function is heart transplantation. Mesenchymal stem cells are multipotent cells found from embryonic mesoderm and found in all tissues. In the field of cardiac regeneration, studies have shown a certain degree of benefit when treated with MSCs from different origins. Our approach is based on a decellularized matrix that carries the cells directly over myocardial infarction.

Detailed Description
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Myocardial infarction causes necrosis of myocardial cells and reduces cardiac function. Today there are treatments such as primary angioplasty and thrombolysis that are effective in limiting cell death after acute myocardial infarction. However, the post-infarct scar often conditions a global ventricular remodeling that can evolve clinically towards heart failure and, in more advanced stages, the only therapy that completely restores cardiac function is heart transplantation. Experimental studies are evaluating new therapeutic approaches based on tissue engineering for myocardial regeneration. Cardiac tissue engineering attempts to create functional tissue constructs that can restore the structure and function of damaged myocardium. Mesenchymal stem cells (MSCs) are multipotent cells that develop from embryonic mesoderm and are found in all structural tissues of the body. In the field of cardiac regeneration, studies have shown a certain degree of benefit when treated with MSCs from different origins. The investigators approach is based on a decellularized matrix that carries the cells directly over myocardial infarction. Among the different types of MSC currently available, the investigators propose the use of those derived from the connective tissue surrounding the great vessels (2 arteries and one vein) of the umbilical cord called Wharton's gelatin (MSC, WJ) whose immunomodulatory properties are described extensively in the literature. These MSC, WJ cells have a PEI approved by the Spanish Agency for Medicines and Healthcare Products (AEMPS) (PEI 16-017) that guarantees an optimal manufacturing process for a clinical trial.

Official Title
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Pericardial Matrix With Mesenchymal Stem Cells for the Treatment of Patients With Infarcted Myocardial Tissue (The PERISCOPE Trial)

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Combination Product: PeriCord: Expanded and cryopreserved allogeneic umbilical cord Wharton´s jelly-derived adult mesenchymal stem cells colonized on human pericardial matrix.
* Procedure: Surgery by sternotomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Myocardial infarction of ≥50% of transmurally due to MR Candidate for coronary by-pass through that or another territory Age ≥18 years Signature of informed consent Wave Q present in the ECG Followed by the cardiology service of Germans Trial i Pujol hospital Exclusion Criteria: Severe valvular disease with indication of surgical repair Candidate for ventricular remodeling Contraindication for MR (creatinine clearance less than 30 ml / min / 1.73m2, metallic implant carriers, claustrophobia) Extracardiac disease with estimated life expectancy less than 1 year Neoplastic disease detected in the last five years or without complete remission Severe renal or hepatic insufficiency Abnormal laboratory values, not explainable at the time of inclusion, and that at the discretion of the investigator contraindicate the patient's participation in the study Patients with a previous cardiac intervention Women who are pregnant or breast-feeding. Women of childbearing age who are heterosexually active and who do not use an effective contraceptive method from 14 days before the inclusion in the study and at least up to 12 weeks after the end of the study. Simultaneous participation in another clinical trial or treatment with another product in investigational phase in the 30 days prior to inclusion in the study. Negation of the patient to be followed by a period that exceeds the clinical trial itself (long-term follow-up in the second and third year).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: - Experimental group: The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization. In addition, the matrix-cell construct will be placed on the ischemic area of the non-candidate revascularization area and will be fixed using surgical glue. - Control group: The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization. No additional procedure will be performed.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization. In addition, the matrix-cell (PeriCord) construct will be placed on the ischemic area of the non-candidate revascularization area and will be fixed using surgical glue. PeriCord: Expanded and cryopreserved allogeneic umbilical cord Wharton´s jelly-derived adult mesenchymal stem cells colonized on human pericardial matrix . | Combination Product: PeriCord: Expanded and cryopreserved allogeneic umbilical cord Wharton´s jelly-derived adult mesenchymal stem cells colonized on human pericardial matrix.<br>* A matrix-cell construct (PeriCord) will be placed on the ischemic area of the non-candidate revascularization area during a surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization.<br>|
| Active Comparator: Control group<br>The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization. No additional procedure will be performed. | Procedure: Surgery by sternotomy<br>* The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization. No additional procedure will be performed only the by-pass.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of death or rehospitalization due to any cause and / or adverse reactions related to the procedure / product under investigation. | Safety measured with a combined endpoint of serious clinical events (death or rehospitalization due to any cause) and serious adverse reactions related to the investigational treatment. | at 12 months of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of death or rehospitalization due to any cause and / or adverse reactions related to the procedure / product under investigation. | Safety measured with a combined endpoint of serious clinical events (death or rehospitalization due to any cause) and serious adverse reactions related to the investigational treatment | At 1 week, 3 and 6 months | 
| Death rate or rehospitalization due to cardiovascular causes | Death rate or rehospitalization due to cardiovascular causes at week, 3, 6 and 12 months. | At 1 week, 3 , 6and 12 months | 
| Rate of relevant arrhythmias in Holter of 24 hours | Rate of relevant arrhythmias in Holter of 24 hours a week, 3 and 12 months. | At 1 week, 3 and 12 months | 
| Relevant changes in N-terminal B-type natriuretic peptide (NT-proBNP) and High sensitivity troponin I (hsTnI) levels | Relevant changes in NT-proBNP and hsTnI levels at week, 3 and 12 months. | At 1 week, 3 and 12 months | 
| Changes in the necrotic myocardial mass ratio | Changes in the necrotic myocardial mass ratio due to gadolinium retention at 3 and 12 months. | At 3 and 12 months | 
| Changes of regional contractility | change of regional contractility by nuclear magnetic resonance (NMR) at 3 and 12 months. | At 3 and 12 months | 
| Changes in ejection fraction of the left ventricle | Changes in ejection fraction of the left at 3 and 12 months | At 3 and 12 months | 
| changes in left and right ventricular geometric remodeling | changes in left and right ventricular geometric remodeling at 3 and 12 months | At 3 and 12 months | 
| Changes in the score on the quality of life test Short Form 36 Healthy Survey (SF-36). | Changes in the score on the quality of life test SF-36 will be used at 3 and 12 months. The mínimum value is 0 and the máximum value is 100. Higher scores mean a better outcome. | At 3 and 12 months | 
| Changes in the score on the quality of life Kansas City Cardiomyopathy Questionnaire (KCCQ) test in cases of participants with heart failure will be used. | Changes in the score on the quality of life test KCCQ in cases of participants with heart failure will be used at 3 and 12 months. The test is composed of 23 items. The options for the answers are Likert scales of 1 to 5, 6 or 7 points and the score of each of its dimensions has a theoretical range from 0 to 100, 100 being the best outcome. | At 3 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac repair, Wharton jelly mesenchymal stem cells, Chronic myocardial infarction, Tissue engineering, Cell therapy, Clinical trial