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CompletedNCT03418233Updated Apr 9, 2021

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

A Phase 2/3 interventional study of CardioCell and Placebos in Heart Failure, sponsored by John Paul II Hospital, Krakow. Completed at 5 sites in Poland. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2021-04-09.

Sponsored by John Paul II Hospital, Krakow · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
115
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Heart Failure

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03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
115 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • DrugCardioCell

    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.

    Also known as: CardioCell administration

  • DrugPlacebos

    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.

    Also known as: Placebo administration

05

What researchers measure

Primary outcomes

  1. 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).

    Time frame: 6 months FU

Secondary outcomes

  1. An increase the result of 6 minute walk test

    An increase the result of 6 minute walk test at 3 and 6 month.

    Time frame: 3 and 6 month FU

  2. Myocardial perfusion improvement

    Myocardial perfusion improvement assessed in SPECT at 6 month FU.

    Time frame: 6 month FU

  3. Myocardial perfusion improvement

    Myocardial perfusion improvement assessed in cardiac MRI at 6 month FU.

    Time frame: 6 month FU

  4. An improvement the result of spiroergometric test

    An improvement the result of spiroergometric test at 6 month FU.

    Time frame: 6 month FU

  5. Left ventricle ejection fraction (LVEF) change against baseline

    Left ventricle ejection fraction (LVEF) change (in %) against baseline, assessed in echocardiography.

    Time frame: 6 month FU

  6. Left ventricle end-systolic volume (ESV) change against baseline

    Left ventricle end-systolic volume (ESV, in ml) change against baseline, assessed in echocardiography.

    Time frame: 6 month FU

  7. Left ventricle end-diastolic volume (EDV) change against baseline

    Left ventricle end-diastolic volume (EDV, in ml) change against baseline, assessed in echocardiography.

    Time frame: 6 month FU

  8. NT pro-BNP level

    NT pro-BNP level at 3, 6 and 12 months in comparison to the baseline level.

    Time frame: 3, 6 and 12 months FU

  9. 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.

    Time frame: 6 month and 1 year FU

  10. 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.

    Time frame: 6 month and 1 year FU

06

Study locations

5 sites
  • The John Paul II Hospital
    Cracovia, 31-202, Poland
  • The University Hospital in Cracow
    Cracovia, 31-501, Poland
  • Instytut Kardiologii im. Prymasa Tysiąclecia Stefana Kardynała Wyszyńskiego
    Katowice, 04-628, Poland
  • Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice
    Katowice, 40-635, Poland
  • Central Clinical Hospital of the MSWiA in Warsaw
    Warsaw, 02-507, Poland
07

Registry details

Key details

Study ID
NCT03418233
Lead sponsor
John Paul II Hospital, Krakow
Collaborators
KCRI, National Center for Research and Development, Poland
Responsible party
Sponsor
First posted
Feb 1, 2018
Start date
Apr 19, 2018
Primary completion
Jan 27, 2021
Completion
Mar 31, 2021
Last update
Apr 9, 2021

Study contacts

Piotr Musiałek, MD, PhD
principal investigator · John Paul II Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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