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)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 115
- 试验地点
- 5
- 主要终点
- Left ventricle ejection fraction (LVEF) increase
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: CardioCell (Drug)
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.
干预措施: Placebos (Drug)
结局指标
主要结局
Left ventricle ejection fraction (LVEF) increase
时间窗: 6 months FU
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).
次要结局
- NT pro-BNP level(3, 6 and 12 months FU)
- The occurrence of major adverse cardiovascular events(6 month and 1 year FU)
- Quality of life improvement(6 month and 1 year FU)
- An improvement the result of spiroergometric test(6 month FU)
- An increase the result of 6 minute walk test(3 and 6 month FU)
- Myocardial perfusion improvement(6 month FU)
- Left ventricle ejection fraction (LVEF) change against baseline(6 month FU)
- Left ventricle end-systolic volume (ESV) change against baseline(6 month FU)
- Left ventricle end-diastolic volume (EDV) change against baseline(6 month FU)