Back to resultsRandomized Clinical Trial to Evaluate the Regenerative Capacity of CardioCell in Patients With Chronic Ischaemic Heart Failure (CIHF)
Primary Purpose
Heart Failure
Status
Completed
Phase
Phase 2
Locations
Poland
Study Type
Interventional
Intervention
CardioCell
Placebos
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure
Eligibility Criteria
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
Sites / Locations
- The John Paul II Hospital
- The University Hospital in Cracow
- Instytut Kardiologii im. Prymasa Tysiąclecia Stefana Kardynała Wyszyńskiego
- Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice
- Central Clinical Hospital of the MSWiA in Warsaw
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Active Group
Control Group
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
An increase the result of 6 minute walk test
An increase the result of 6 minute walk test at 3 and 6 month.
Myocardial perfusion improvement
Myocardial perfusion improvement assessed in SPECT at 6 month FU.
Myocardial perfusion improvement
Myocardial perfusion improvement assessed in cardiac MRI at 6 month FU.
An improvement the result of spiroergometric test
An improvement the result of spiroergometric test at 6 month FU.
Left ventricle ejection fraction (LVEF) change against baseline
Left ventricle ejection fraction (LVEF) change (in %) against baseline, assessed in echocardiography.
Left ventricle end-systolic volume (ESV) change against baseline
Left ventricle end-systolic volume (ESV, in ml) change against baseline, assessed in echocardiography.
Left ventricle end-diastolic volume (EDV) change against baseline
Left ventricle end-diastolic volume (EDV, in ml) change against baseline, assessed in echocardiography.
NT pro-BNP level
NT pro-BNP level at 3, 6 and 12 months in comparison to the baseline level.
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.
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.
Full Information
NCT ID
NCT03418233
First Posted
January 25, 2018
Last Updated
April 8, 2021
Sponsor
John Paul II Hospital, Krakow
Collaborators
KCRI, National Center for Research and Development, Poland
1. Study Identification
Unique Protocol Identification Number
NCT03418233
Brief Title
Randomized Clinical Trial to Evaluate the Regenerative Capacity of CardioCell in Patients With Chronic Ischaemic Heart Failure (CIHF)
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
April 19, 2018 (Actual)
Primary Completion Date
January 27, 2021 (Actual)
Study Completion Date
March 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
John Paul II Hospital, Krakow
Collaborators
KCRI, National Center for Research and Development, Poland
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model 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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The Data and Safety Monitoring Board (DSMB) will be blinded at project start, but may request unblinding if necessary to accommodate effective review of data.
Other than the DSMB (if necessary), the only other "un-blinded parties", meaning that they will have knowledge as to the patient's treatment assignment, will be the PBTiK UJ CM employee who participates in randomization utilizing randomization lists and investigational medication preparation.
Allocation
Randomized
Enrollment
115 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active Group
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Control Group
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
CardioCell
Other Intervention Name(s)
CardioCell administration
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebos
Other Intervention Name(s)
Placebo administration
Intervention Description
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.
Primary Outcome Measure Information:
Title
Left ventricle ejection fraction (LVEF) increase
Description
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).
Time Frame
6 months FU
Secondary Outcome Measure Information:
Title
An increase the result of 6 minute walk test
Description
An increase the result of 6 minute walk test at 3 and 6 month.
Time Frame
3 and 6 month FU
Title
Myocardial perfusion improvement
Description
Myocardial perfusion improvement assessed in SPECT at 6 month FU.
Time Frame
6 month FU
Title
Myocardial perfusion improvement
Description
Myocardial perfusion improvement assessed in cardiac MRI at 6 month FU.
Time Frame
6 month FU
Title
An improvement the result of spiroergometric test
Description
An improvement the result of spiroergometric test at 6 month FU.
Time Frame
6 month FU
Title
Left ventricle ejection fraction (LVEF) change against baseline
Description
Left ventricle ejection fraction (LVEF) change (in %) against baseline, assessed in echocardiography.
Time Frame
6 month FU
Title
Left ventricle end-systolic volume (ESV) change against baseline
Description
Left ventricle end-systolic volume (ESV, in ml) change against baseline, assessed in echocardiography.
Time Frame
6 month FU
Title
Left ventricle end-diastolic volume (EDV) change against baseline
Description
Left ventricle end-diastolic volume (EDV, in ml) change against baseline, assessed in echocardiography.
Time Frame
6 month FU
Title
NT pro-BNP level
Description
NT pro-BNP level at 3, 6 and 12 months in comparison to the baseline level.
Time Frame
3, 6 and 12 months FU
Title
The occurrence of major adverse cardiovascular events
Description
The occurrence of major adverse cardiovascular events (MACE including death, myocardial infarction, and hospitalization for heart failure) at 6 month and 1 year FU.
Time Frame
6 month and 1 year FU
Title
Quality of life improvement
Description
Quality of life improvement, assessed by SF-36 questionnaire or other dedicated for investigated population at 6 month and 1 year FU.
Time Frame
6 month and 1 year FU
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Piotr Musiałek, MD, PhD
Organizational Affiliation
John Paul II Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
The John Paul II Hospital
City
Cracovia
ZIP/Postal Code
31-202
Country
Poland
Facility Name
The University Hospital in Cracow
City
Cracovia
ZIP/Postal Code
31-501
Country
Poland
Facility Name
Instytut Kardiologii im. Prymasa Tysiąclecia Stefana Kardynała Wyszyńskiego
City
Katowice
ZIP/Postal Code
04-628
Country
Poland
Facility Name
Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice
City
Katowice
ZIP/Postal Code
40-635
Country
Poland
Facility Name
Central Clinical Hospital of the MSWiA in Warsaw
City
Warsaw
ZIP/Postal Code
02-507
Country
Poland
12. IPD Sharing Statement
Learn more about this trial
Randomized Clinical Trial to Evaluate the Regenerative Capacity of CardioCell in Patients With Chronic Ischaemic Heart Failure (CIHF)
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