Multi-intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Heart Failure With Reduced Ejection Fraction（PRIME-HFrEF Study）

Study Overview
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Brief Summary
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This study is an exploratory clinical study to observe the safety and efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in the heart failure patients with reduced ejection fraction. The study was a 12 months single center, randomized, double-blind, placebo-controlled trial that included 12 weeks of treatment, and 9 months of follow-up.

Detailed Description
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The study was a 12-month single center, randomized, double-blind, placebo-controlled trial that included 12 weeks of treatment, and 9 months of follow-up.We plan to recruit 40 subjects，which were divided into experimental group and control group. The volunteers of the experimental group will be given peripheral intravenously infusion a dose of 1.0*10^6/kg human umbilical cord mesenchymal stem cell (HUC-MSC) respectively at 0,6,12 week. The control group will be given the same dose of 1 percent human serum albumin injection. Then centralization visit was conducted at 0,7 day, 6,12 week, 6 and 12 month. The primary safety end point is the incidence of any treatment emergent serious adverse events within12 months after intravenous MSC infusion, including death, nonfatal MI, stroke, sustained ventricular arrhythmias (>15 seconds or causing hemodynamic compromise), and other adverse events such as infection, tumor formation and clinical abnormal, which will be evaluated by monitoring for serial troponin, hematology, chemistry, urinalysis, 24-hour Holter, CTscans and ultrasound of abdomen.There are independent data and safety monitoring committees to monitor patient safety throughout the duration the trial.The primary efficacy endpoint is a change in Left Ventricular Ejection Fractions (LVEF) measured by left ventricular opacification (LVO) with contrast echocardiography and magnetic resonance imaging (MRI) at 12th month.

Official Title
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Multi-intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells for Treatment in Heart Failure Patients With Reduced Ejection Fraction: A Randomized, Double Blind, Placebo-Controlled, Prospective Clinical Study

Conditions
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Heart Failure, Systolic

Intervention / Treatment
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* Biological: human umbilical cord mesenchymal stem cells
* Other: human serum albumin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: LVEF≤40％; NYHA II-IV; Received maximally tolerated guideline-directed medical therapy ( GDMT) for at least 3 months before enrollment; Angiography or coronary CT within 6 months shows that there is no indication for PCI / CABG; Or PCI / CABG indications, but refused. Exclusion Criteria: Severe valvular heart disease, congenital heart disease, acute viral myocarditis and acute coronary syndrome. PCI / CABG, ICD / permanent pacemaker / CRT implantation within 3 months. Recent cerebrovascular disease (<6 months). eGFR<30ml/min, or ALT/AST>120U/L. Hematologic disease: anemia (hemoglobin ≤9.0 g/dL); leukopenia (<3500/μL); thrombocytopenia (<70000/μL); myeloproliferative disorders, myelodysplastic syndrome, acute or chronic leukemia, and plasma cell dyscrasias (multiple myeloma, amyloidosis) . Malignant tumor within 5 years. Life expectancy <1 year according any disease. Uncontrolled acute infectious diseases. Known or suspected of being sensitive to the study drugs or its ingredients. Not suitable for inclusion according to the evaluation of the sponsors or unwilling to comply with the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group<br>The volunteers of the experimental group will be given peripheral intravenously a dose of 1.0*10^6/kg human umbilical cord mesenchymal stem cells at 0,6,12 week. | Biological: human umbilical cord mesenchymal stem cells<br>* Human umbilical cord mesenchymal stem cells were peripheral intravenous infused to experimental group.<br>|
| Placebo Comparator: control group<br>The control group will be given the same dose of saline containing human albumin. | Other: human serum albumin<br>* Saline solution containing 1 percent human serum albumin will be infused to the control group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety of treatment | The incidence of treatment related adverse events | Day 360 | 
| Left ventricular ejection fraction | The change in Left ventricular ejection fraction (LVEF) % after the infusion. | Day 360 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite of cardiac death and rehospitalization caused by heart failure within 12 months | The comparison of the mortality and the incidence of rehospitalization caused by heart failure between the two groups. | 12 month after treatment | 
| NT-proBNP | The change in NT-proBNP after the infusion. | Day 360 | 
| ST2 | The change in ST2 after the infusion. | Day 360 | 
| Left ventricular end systolic volume | The change in Left ventricular end systolic volume(LVESV) after the infusion | Day 43, Day 85, Day 180, Day 360 | 
| 6 minutes walking distance | The change in 6 minutes walking distance after the infusion. | Day 360 | 
| The SUV in PET-MR | The change of standard uptake value in PET-MR after the infusion | Day 180 | 
| Right ventricular end systolic volume | The change in Right ventricular end systolic volume(RVESV) after the infusion | Day 360 | 
| Tricuspid annular plane systolic excursion | Changes of Right ventricular tricuspid annular plane systolic excursion (TAPSE) detected by echocardiography | Day 360 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Umbilical Cord Mesenchymal Stem Cells, Heart Failure