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

Phase 1

Completed

• Conditions: Heart Failure, Systolic
• Interventions: Biological: human umbilical cord mesenchymal stem cells; Other: human serum albumin

• Registration Number: NCT04992832
• Lead Sponsor: Shanghai East Hospital

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.

Study Timeline

• Study First Submitted: 2021-07-13
• Study Start: 2021-07-28
• Study First Submitted QC: 2021-07-29
• Study First Posted: 2021-08-05
• Primary Completion: 2023-01-17
• Study Completion: 2023-04-04
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-30
• Last Update Posted: 2023-12-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
experimental group	human umbilical cord mesenchymal stem cells	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.
control group	human serum albumin	The control group will be given the same dose of saline containing human albumin.

Primary Outcome Measures

Name	Time	Method
Left ventricular ejection fraction	Day 360	The change in Left ventricular ejection fraction (LVEF) % after the infusion.
The safety of treatment	Day 360	The incidence of treatment related adverse events

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Heart Failure Department, East Hospital Affiliated to Tongji University; 🇨🇳 Shanghai, Shanghai, China