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

Phase 1Not Yet RecruitingNCT06956807

Viscofan10 enrolled

Overview

* 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.

Study Type

INTERVENTIONAL

Allocation

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

combination of MACCEs at all follow up visits during the first year after treatment

combination of MACCEs at all follow up visits during the first year after treatment (after surgery, at 1, 3, 6, 9 and 12 months). MACCEs are defined as all cause death, myocardial infarction requiring target vessel revascularisation, hospitalisation for heart failure, cardiac tamponade or pericardial constriction, sustained ventricular tachycardia, ventricular fibrillation, and stroke.

Time frame: 12 months

Secondary Outcomes

Safety - Composite MACCE

Composite MACCE (all cause death, myocardial infarction requiring target vessel revascularisation, hospitalisation for heart failure, cardiac tamponade or pericardial constriction, sustained ventricular tachycardia, ventricular fibrillation, and stroke) at all follow up visits during the first year after treatment (after surgery, 1, 3, 6, 9 and 12 months),

Time frame: 12 months

Safety - Hematology parameters

Erythrocytes, Haemoglobin, Haematocrit, Leukocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, Prothrombin time, APTT, INR. Measurement of the values and evaluation of their clinical significance in case they are outside of the normal range.

Time frame: 12 months

Safety - Adverse Events

Any cause adverse event at all follow up visits during the first year after treatment (after surgery, 1, 3, 6, 9 and 12 months)

Time frame: 12 months

Safety - Biochemical blood parameters

Measurement of biochemistry paramenters in blood including Glucose, Creatinine, Urea, GOT, GPT, GGT, Total bilirubin, Alkaline phosphatase, Total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, Total proteins, Sodium, Potassium, Calcium, Chloride. Evaluation of clinical significance in case values are out of normal range.

Time frame: 12 months

Safety - New York Heart Association (NYHA) functional class

Assessment of the New York Heart Association (NYHA) functional class before surgery (the first assessment will be done during the screening process and repeated before the procedure), at 6 and 12 months after surgery.

Time frame: 12 months

Safety - Minnesota Living with Heart Failure (MLHFQ) questionnaire

Minnesota Living with Heart Failure (MLHFQ) questionnaire, before surgery (the first assessment will be done during the screening process, at least one day before surgery), at 6 and 12 months after surgery.

Time frame: 12 months

Safety - 6 minute walk test

The 6 minute walk test will be performed before surgery (the first assessment will be done during the screening process, at least one day before surgery), at 6 and 12 months after surgery.

Time frame: 12 months

Safety - Brain natriuretic peptide curve (Nt proBNP or BNP)

Brain natriuretic peptide curve (Nt proBNP or BNP, depending on the availability at each site using the same parameter throughout the follow up of each patient). Levels will be measured during the screening process (the first assessment will be done, at least one day before surgery), on the second day after surgery and at 6 and 12 months after product administration.

Time frame: 12 months

Safety - C reactive protein (CRP) levels

C reactive protein (CRP) levels will be assessed prior to surgery (the first assessment will be done during the screening process, repeated prior to surgery), at hospital discharge, and 1 month after product administration.

Time frame: 1 month

Safety - Incidence of subacute pericardial inflammation or constrictive physiology

Incidence of subacute pericardial inflammation or constrictive physiology as assessed by echocardiography and cardiac magnetic resonance imaging (CMRI) at months 1, 6 and 12 after treatment. The first assessment will be done during the screening process.

Time frame: 12 months

Safety - Immunological analysis

The following immunological analysis will be performed: B Lymphocytes, NK Lymphocytes (CD16+), T Lymphocytes (CD3+), Th Lymphocytes (CD4+), Activated Th Lymphocytes (CD4+DR+), Treg Lymphocytes (CD4+CD25+), Treg Lymphocytes (CD4+CD25+), Activated Treg Lymphocytes (CD4+CD25+DR+), Cytotoxic T Lymphocytes (CD8+), Activated Cytotoxic T Lymphocytes (CD8+DR+), Cytotoxic Treg Lymphocytes (CD8+CD25+), Activated Cytotoxic Treg Lymphocytes (CD8+CD25+DR+), Albumin, Alpha globulin, Beta globulin, Gamma globulin, IgG, IgM and anti-HLA antibodies (the first assessment will be done during the screening process) at discharge (at discharge excluding Serum Cytokines and anti-HLA antibodies) and 1 month after product administration.

Time frame: 1 month

Efficacy - Change in scar size

Absolute change in scar size expressed as percentage of left ventricular mass (i.e. scar mass corrected for total left ventricular mass), absolute change in percentage of viable left ventricular mass (i.e. viable mass corrected for total left ventricular mass), absolute change in total scar size (expressed in grams), and absolute change in viable mass (expressed in grams).

Time frame: 12 months

Efficacy - end systolic volume

Biomechanical parameters of the left ventricle: end systolic volume, end diastolic volume, ejection fraction, segmental contractility, and segmental wall thickness. All values will be obtained by CMRI analysis.

Time frame: 12 months

Efficacy - end diastolic volume

Time frame: 12 months

Efficacy - ejection fraction

Time frame: 12 months

Efficacy - segmental contractility

Time frame: 12 months

Efficacy - segmental wall thickness

Time frame: 12 months

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts