Evaluation of the CIRCULATE Catheter for Transcoronary Administration of Pharmacologic and Cell-based Agents

Study Overview
=================
Brief Summary
-----------------
Clinical evaluation of the CIRCULATE catheter involves intracoronary administration of a typical medical agent (nitroglycerin) and a shown-to-be-safe cell-based agent (CardioCell) in patients with a diagnosis of dilated cardiomyopathy (DCM).

Detailed Description
-----------------
The use of adult stem cells from several sources has been shown to improve cardiac function in acute and chronic cardiac disease. Several sources of adult stem cells have been identified including bone marrow, skeletal muscle, blood and adipose tissue. A number of pilot trials using intramyocardial injection of stem cells have shown promising results in patients with chronic myocardial disease in patients with ischemic heart failure , and in patients after an acute myocardial infarction . The vast majority of research on cell therapies in the treatment of heart diseases focuses mainly on determining the optimal source of cells, their characteristics, and the number of cells in the administered preparation. From a clinical perspective, the method of cell administration is also an important topic. There are several ways of cell administration that can be used in cell therapy for heart muscle disease. In addition to the intramuscular administration systems, such preparations can be administered directly into the circulation in a more or less selective manner. As no dedicated devices were developed, various types of catheters and microcatheters have been used for transcoronary administration. During the procedure of administering cell preparations by means of a catheter directly to the selected coronary vessel, the flow parameters should be adjusted to minimize the risk of damage to the administered cells. The CIRCULATE catheter tested in the experiment was designed to increase the efficacy and safety of the cells delivery. It has a reservoir and holes created through which - as shown in preclinical studies - the cells can be delivered without a risk of their damage during delivery. In addition to the administration of cell therapy, the course of the study is planned to administer the drug - nitroglycerin - one of the most commonly used drugs for coronary administration, recommended during standard angiography of the coronary arteries due to its ability to expand the arterial bed, thus enabling accurate imaging and sizing of the examined arteries.

Official Title
-----------------
Evaluation of the CIRCULATE Catheter for Transcoronary Administration of Pharmacologic and Cell-based Agents

Conditions
-----------------
Dilated Cardiomyopathy

Intervention / Treatment
-----------------
* Device: Transcoronary delivery of a pharmacological agent (nitroglycerin) and cell based agent (Cardiocell) using the CIRCULATE Catheter


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of DCM Left ventricular ejection fraction (LVEF) ≤ 45% by echocardiography Signed informed consent Exclusion Criteria: Less than 3 months from any substantial cardiac therapeutic intervention (such as, e.g. CRT/ICD fitting) Less than 3 months from acute coronary syndrome BMI lower than 18 or greater than 45kg/m2 Severe valvular heart disease or left ventricle aneurysm requiring aneurysmectomy or other structural interventions Present candidate for heart transplantation Active or any history of malignancy or tumor Moderate or severe immunodeficiency Chronic immunosuppressive therapy Acute or chronic infection Coagulopathies Known alcohol or drug dependence Severe renal dysfunction (eGFR<20mL/min) Soft tissue disease or local infection in a place of required artery puncture Pregnancy or breastfeeding Females of childbearing potential who do not use a highly effective method of contraception, and in absence of a negative highly sensitive urine or serum pregnancy test Participation in any other clinical research study that has not reached its primary efficacy endpoint or otherwise would interfere with the patient's participation in this project Life expectancy <12 months Any concurrent disease or condition that, in the opinion of the investigator, would make the patient unsuitable for participation in the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Interventional Model Description: Clinical evaluation of the CIRCULATE catheter will be performed in a group of 10 patients. Each will receive intracoronary NTG followed by labelled CardioCell. This is a non-randomized study without any requirement for sample size calculation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CIRCULATE Catheter<br>CIRCULATE Catheter will be used to deliver nitroglycerin and CardioCell to evaluate safety and efficacy of the device | Device: Transcoronary delivery of a pharmacological agent (nitroglycerin) and cell based agent (Cardiocell) using the CIRCULATE Catheter<br>* Investigated device - the CIRCULATE Catheter will be introduced, using a standard radial or femoral access and a typical guiding catheter and typical coronary wire, first into the right coronary artery. After that the one dose of NTG (200µg) will be administered followed by a typical angiographic recording to visualize the vasodilatatory effect of the medication. Then CardioCell in doses of 10mln cells each (6.7mL) will be administered transcoronary to each of the coronary arteries (right coronary artery (RCA), LAD, left circumflex (Cx)). Angiography will be performed routinely before and after each product administration.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device success | Device success, defined as the device introduction, administration of nitroglycerine and cell-based agent, and device removal without complications | During procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standardized uptake values (SUVs) of 99mTc-HMPAO radiolabelled CardioCell | CardioCell myocardial uptake on a whole-body scan: 50% of cells will be radiolabelled. Standardized uptake values (SUVs) of 99mTc-HMPAO radiolabelled CardioCell in cardiac VOI on a whole-body scan measured using the commercial calculation methods corrected for physical decay and attenuation | 1 hour after application | 
| Freedom from major adverse cardiovascular events | Freedom from periprocedural (during the procedure and 60 minutes thereafter) major adverse cardiovascular events | 24 hours or until hospital discharge, whichever time point is first |