Safety and Efficacy of Epicardial Implantation of Collagen Membranes With Allogeneic Adipose Derived Stem Cells

First in Human Open Label Multicentre Clinical Trial to Evaluate the Safety and Efficacy of Epicardial Implantation of Collagen Membranes With Allogeneic Adipose Derived Stem Cells in Patients With Ischaemic Left Ventricular Dysfunction Scheduled to Undergo Coronary Revascularisation Surgery

• The Cardiomesh II clinical trial is a phase I open label study intended to enrol 10 patients to evaluate the safety and efficacy of surgical epicardial implantation of a membrane seeded with allogeneic adipose tissue derived stem cells in patients scheduled to undergo coronary revascularisation surgery and at high risk of developing heart failure.
• The primary objective of the study is to evaluate the safety of surgical implantation of this membrane in patients with large ischaemic myocardial scars scheduled to undergo coronary revascularisation surgery. The secondary objective is to investigate the efficacy of the above treatment in terms of reduction of scar size and ventricular function parameters.

• The clinical trial CARDIOMESH II aims to attenuate adverse remodelling of the left ventricle, which is the main cause of death in ischaemic heart disease, through the development of a new regenerative therapy consisting of the combination of allogeneic adipose derived stem cells with bovine derived collagen membranes to promote repair of damaged myocardium. This is predicted to achieve a 10% reduction in mortality related to ischaemic heart failure.
• Specifically, the working hypotheses of the project are:
• Surgical implantation of a membrane containing allogeneic adipose derived stem cells in patients with large myocardial scars scheduled to undergo coronary revascularisation surgery is technically feasible.
• Surgical implantation of a membrane containing allogeneic adipose derived stem cells in patients with large myocardial scars scheduled to undergo coronary revascularisation surgery is safe in terms of the primary objective consisting of major adverse cardiac and cerebrovascular events (MACCEs).
• Surgical implantation of the aforementioned bioengineering product is safe in terms of cardiac effects and immunological analysis.
• Surgical implantation of this cellularised membrane shows beneficial effects in terms of efficacy measured by surrogate cardiac imaging parameters.
• Designed as an international phase I clinical trial to be conducted at two sites in two European countries, the purpose of the study is to establish the basic safety parameters and to obtain preliminary efficacy data on clearly established surrogate variables to undertake future larger scale trials focused on clinical efficacy.

Inclusion Criteria:

1. Patients planning to undergo coronary revascularisation surgery within one month of study entry.
2. LVEF ≤45% by CMRI.
3. History of myocardial infarction at least 3 months prior to inclusion.
4. Scar covering at least 15% of the total left ventricular myocardial mass defined by late enhancement on CMRI.

Exclusion Criteria:

1. Participation in another clinical trial within 30 days prior to inclusion.
2. Prior treatment with cell or gene therapy.
3. Be a candidate for heart transplant at the time of study entry.
4. Diagnosis of acute myocardial infarction with 3 months prior to inclusion.
5. Need for urgent revascularisation surgery.
6. Strict contraindication for the use of CMRI (pacemaker or implantable automatic defibrillator carriers, previous reactions to gadolinium contrast, claustrophobia, cochlear implants, etc.).
7. Presence of uncontrolled ventricular arrhythmias (ventricular tachycardia or ventricular fibrillation) at the time of implant surgery.
8. Active systemic infection.
9. Women who are pregnant or breastfeeding.
10. Mental disease or psychological condition that impedes the subject from understanding the nature of the protocol and granting his/her consent
11. Advanced dementia according to the Barthel index.
12. History of primary or acquired immunodeficiency or on immunosuppressive therapy (within 3 months prior to inclusion or if the need for immunotherapy is foreseeable at any time during the study follow up).
13. Tumour disease, except that eradicated at least 5 years prior to inclusion in the study and without receiving chest radiotherapy. Completely eradicated non melanoma skin tumours (at any time) not requiring chest chemotherapy or radiotherapy are permitted.
14. History of autoimmune disease.
15. Stroke within 12 months prior to inclusion.
16. Respiratory compromise or need for home oxygen therapy.
17. Life expectancy of less than 1 year for any reason