Randomized Clinical Trial to Evaluate the Regenerative Capacity of CardioCell in Patients With Chronic Ischaemic Heart Failure (CIHF)

Regeneration of Ischemic Damages in Cardiovascular System Using Wharton's Jelly as an Unlimited Source of Mesenchymal Stem Cells for Regenerative Medicine. Project of the National Centre for Research and Development (Poland) 'STRATEGMED II'. Randomized Clinical Trial to Evaluate the Regenerative Capacity of CardioCell in Patients With Chronic Ischaemic Heart Failure (CIHF)

The main objective of the CIRCULATE project is to compare the clinical outcomes of CardioCell administration in treatment of ischemic damages of cardiovascular system with control group, who will receive the placebo.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: CardioCell; Drug: Placebos

Detailed Description

The CIHF trial will enroll 105 patients with randomization into active and placebo therapy with 2:1 ratio.

Additional 5-10 subjects meeting inclusion/exclusion criteria will receive, in a non-blinded fashion, labelled CardioCell to determine the early myocardial uptake and retention of IMP.

The primary research question of this project is to check if the administration of CardioCell could improve the clinical outcomes in patients with CIHF. There are several secondary questions, defined by secondary endpoints in each cohort, e.g.: if the investigated treatment is possible to administered, if the investigated treatment and way of CardioCell administration is safe, if it is possible to define any selected subgroup in which the treatment results are significantly different than in whole group.

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Poland
  • Cracovia, Poland, 31-202
    • The John Paul II Hospital
  • Cracovia, Poland, 31-501
    • The University Hospital in Cracow
  • Katowice, Poland, 40-635
    • Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice
  • Katowice, Poland, 04-628
    • Instytut Kardiologii im. Prymasa Tysiąclecia Stefana Kardynała Wyszyńskiego
  • Warsaw, Poland, 02-507
    • Central Clinical Hospital of the MSWiA in Warsaw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged 18-80 years
• Diagnosis of ischemic heart failure (supported by history of CAD or revascularization by PCI or CABG procedure) without known need for revascularization or feasibility of revascularization
• Substantial chronic ischemic myocardial injury as demonstrated by LVEF ≤45% by SPECT and the clinical stage of NYHA II or III
• At least 50% viable myocardium (SPECT)
• Patency of at least two major coronary arteries and/or bypass grafts supplying their territories (confirmed in angiography within 12 months)
• Clinically stable CIHF for at least 3 months on guideline recommended therapy
• Signed informed consent

Exclusion Criteria:

• Other than ischemic cause of cardiomyopathy
• Less than 3 months from any substantial therapeutic intervention (such as, e.g. CRT/ICD fitting or revascularization)
• Less than 3 months from ACS
• BMI lower than 18 or greater than 45kg/m2
• Severe valvular heart disease or left ventricle aneurysm requiring aneurysmectomy or other structural interventions
• 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
• Females of childbearing potential in absence of a negative highly sensitive urine or serum pregnancy test
• Participation in any other clinical research study that has not reached the primary efficacy endpoint or otherwise would interfere with the patient's participation in this project
• Life expectancy < 12 months
• Any objective or subjective reason for inability to attend follow-up visits
• Any concurrent disease or condition that, in the opinion of the investigator, would make the patient unsuitable for participation in the project

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Group; Patients randomized to the active treatment group: Transcoronary or trans-bypass graft administration of CardioCell consist 30 000 000 cells (suspended in 20 ml of 0.9% NaCl and 5% albumin) will be performed using a dedicated cell delivery catheter. The cell delivery catheter is a typical coronary balloon catheter that is CE marked (1.2x10 mm balloon, RX system) modified to include cell delivery perforations in the balloon section of the catheter. The cell delivery catheter has been demonstrated not to affect cell viability or other cell properties.	Drug: CardioCell; Patients randomized to the active treatment group will receive transcoronary or trans-bypass graft administration of 30 000 000 cells (suspended in 20 ml of 0.9% NaCl and 5% albumin). Injection will be performed using a dedicated cell delivery catheter. The cell delivery catheter is a typical coronary balloon catheter that is CE marked (1.2x10 mm balloon, RX system) modified to include cell delivery perforations in the balloon section of the catheter. The cell delivery catheter has been demonstrated not to affect cell viability or other cell properties.; Other Names: CardioCell administration
Placebo Comparator: Control Group; Patients randomized to the placebo group will receive Placebos consist 0.9% NaCl and 5% albumin injections (in the same volumes as CardioCell) via the coronary arter(ies)/bypass grafts. The CardioCell and placebo are distributed encoded, in an indistinguishable form.	Drug: Placebos; Patients randomized to the placebo group will receive Placebos consist 0.9% NaCl and 5% albumin injections (in the same volumes as CardioCell) via the coronary arter(ies)/bypass grafts. The CardioCell and placebo are distributed encoded, in an indistinguishable form.; Other Names: Placebo administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricle ejection fraction (LVEF) increase	Left ventricle ejection fraction (LVEF) increase, assessed by SPECT at 6M FU vs. during index (baseline) imaging - comparison between two groups (active vs placebo therapy).	6 months FU

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
An increase the result of 6 minute walk test	An increase the result of 6 minute walk test at 3 and 6 month.	3 and 6 month FU
Myocardial perfusion improvement	Myocardial perfusion improvement assessed in SPECT at 6 month FU.	6 month FU
Myocardial perfusion improvement	Myocardial perfusion improvement assessed in cardiac MRI at 6 month FU.	6 month FU
An improvement the result of spiroergometric test	An improvement the result of spiroergometric test at 6 month FU.	6 month FU
Left ventricle ejection fraction (LVEF) change against baseline	Left ventricle ejection fraction (LVEF) change (in %) against baseline, assessed in echocardiography.	6 month FU
Left ventricle end-systolic volume (ESV) change against baseline	Left ventricle end-systolic volume (ESV, in ml) change against baseline, assessed in echocardiography.	6 month FU
Left ventricle end-diastolic volume (EDV) change against baseline	Left ventricle end-diastolic volume (EDV, in ml) change against baseline, assessed in echocardiography.	6 month FU
NT pro-BNP level	NT pro-BNP level at 3, 6 and 12 months in comparison to the baseline level.	3, 6 and 12 months FU
The occurrence of major adverse cardiovascular events	The occurrence of major adverse cardiovascular events (MACE including death, myocardial infarction, and hospitalization for heart failure) at 6 month and 1 year FU.	6 month and 1 year FU
Quality of life improvement	Quality of life improvement, assessed by SF-36 questionnaire or other dedicated for investigated population at 6 month and 1 year FU.	6 month and 1 year FU

Collaborators and Investigators

• Sponsor: John Paul II Hospital, Krakow
• Collaborators: National Center for Research and Development, Poland; KCRI
• Investigators: Principal Investigator: Piotr Musiałek, MD, PhD, John Paul II Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2018
• Primary Completion (Actual): January 27, 2021
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: January 25, 2018
• First Submitted That Met QC Criteria: January 25, 2018
• First Posted (Actual): February 1, 2018

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CardioCell in CIHF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No