Clinical trial NCT04992832: Multi-intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Heart Failure With Reduced Ejection Fraction（PRIME-HFrEF Study）
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Heart Failure, Systolic
Keywords: Human Umbilical Cord Mesenchymal Stem Cells
Heart Failure
Lead sponsor: Shanghai East Hospital
Sponsor class: OTHER
First posted: 2021-08-05
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. LVEF≤40％;
2. NYHA II-IV;
3. Received maximally tolerated guideline-directed medical therapy ( GDMT) for at least 3 months before enrollment;
4. Angiography or coronary CT within 6 months shows that there is no indication for PCI / CABG; Or PCI / CABG indications, but refused.

Exclusion Criteria:

1. Severe valvular heart disease, congenital heart disease, acute viral myocarditis and acute coronary syndrome.
2. PCI / CABG, ICD / permanent pacemaker / CRT implantation within 3 months.
3. Recent cerebrovascular disease (\<6 months).
4. eGFR\<30ml/min, or ALT/AST\>120U/L.
5. 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) .
6. Malignant tumor within 5 years.
7. Life expectancy \<1 year according any disease.
8. Uncontrolled acute infectious diseases.
9. Known or suspected of being sensitive to the study drugs or its ingredients.
10. Not suitable for inclusion according to the evaluation of the sponsors or unwilling to comply with the study protocol.

Primary outcomes:
measure: The safety of treatment
timeFrame: Day 360
measure: Left ventricular ejection fraction
timeFrame: Day 360
Secondary outcomes:
measure: A composite of cardiac death and rehospitalization caused by heart failure within 12 months
timeFrame: 12 month after treatment
measure: NT-proBNP
timeFrame: Day 360
measure: ST2
timeFrame: Day 360
measure: Left ventricular end systolic volume
timeFrame: Day 43, Day 85, Day 180, Day 360
measure: 6 minutes walking distance
timeFrame: Day 360
measure: The SUV in PET-MR
timeFrame: Day 180
measure: Right ventricular end systolic volume
timeFrame: Day 360
measure: Tricuspid annular plane systolic excursion
timeFrame: Day 360
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Heart Failure Department, East Hospital Affiliated to Tongji University
state: Shanghai
Study officials:
affiliation: Shanghai East Hospital, Shanghai Tongji University
name: Zhongmin Liu, Doctor
role: PRINCIPAL_INVESTIGATOR
References: