Clinical trial NCT03418233: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Heart Failure
Lead sponsor: John Paul II Hospital, Krakow
Sponsor class: OTHER
Collaborators: name: KCRI
name: National Center for Research and Development, Poland
First posted: 2018-02-01
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Left ventricle ejection fraction (LVEF) increase
timeFrame: 6 months FU
Secondary outcomes:
measure: An increase the result of 6 minute walk test
timeFrame: 3 and 6 month FU
measure: Myocardial perfusion improvement
timeFrame: 6 month FU
measure: Myocardial perfusion improvement
timeFrame: 6 month FU
measure: An improvement the result of spiroergometric test
timeFrame: 6 month FU
measure: Left ventricle ejection fraction (LVEF) change against baseline
timeFrame: 6 month FU
measure: Left ventricle end-systolic volume (ESV) change against baseline
timeFrame: 6 month FU
measure: Left ventricle end-diastolic volume (EDV) change against baseline
timeFrame: 6 month FU
measure: NT pro-BNP level
timeFrame: 3, 6 and 12 months FU
measure: The occurrence of major adverse cardiovascular events
timeFrame: 6 month and 1 year FU
measure: Quality of life improvement
timeFrame: 6 month and 1 year FU
Other outcomes:
Locations:
city: Cracovia
country: Poland
facility: The John Paul II Hospital
city: Cracovia
country: Poland
facility: The University Hospital in Cracow
city: Katowice
country: Poland
facility: Instytut Kardiologii im. Prymasa Tysiąclecia Stefana Kardynała Wyszyńskiego
city: Katowice
country: Poland
facility: Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice
city: Warsaw
country: Poland
facility: Central Clinical Hospital of the MSWiA in Warsaw
Study officials:
affiliation: John Paul II Hospital
name: Piotr Musiałek, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: