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

Heart Failure, Systolic Clinical Trial

— PRIME-HFrEF  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04992832
• Other study ID #: DFSC-2018(CR)-08
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 28, 2021
• Est. completion date: April 4, 2023

Study information

• Verified date: November 2023
• Source: Shanghai East Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 4, 2023
• Est. primary completion date: January 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Systolic

Intervention

Biological:
• human umbilical cord mesenchymal stem cells
Human umbilical cord mesenchymal stem cells were peripheral intravenous infused to experimental group.

Other:
• human serum albumin
Saline solution containing 1 percent human serum albumin will be infused to the control group.

Locations

Country	Name	City	State
China	Heart Failure Department, East Hospital Affiliated to Tongji University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai East Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The safety of treatment	The incidence of treatment related adverse events	Day 360
Primary	Left ventricular ejection fraction	The change in Left ventricular ejection fraction (LVEF) % after the infusion.	Day 360
Secondary	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
Secondary	NT-proBNP	The change in NT-proBNP after the infusion.	Day 360
Secondary	ST2	The change in ST2 after the infusion.	Day 360
Secondary	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
Secondary	6 minutes walking distance	The change in 6 minutes walking distance after the infusion.	Day 360
Secondary	The SUV in PET-MR	The change of standard uptake value in PET-MR after the infusion	Day 180
Secondary	Right ventricular end systolic volume	The change in Right ventricular end systolic volume(RVESV) after the infusion	Day 360
Secondary	Tricuspid annular plane systolic excursion	Changes of Right ventricular tricuspid annular plane systolic excursion (TAPSE) detected by echocardiography	Day 360