Multi-dose mesenchymal stem cell (MSC) regimens have not been widely evaluated for safety in patients with heart failure with reduced ejection fraction (HFrEF). A randomized trial assessed the safety of repeated intravenous MSC infusions, with exploratory evaluation of cardiac function parameters.

The PRIME-HFrEF (Prospective Randomized Controlled Study of Multiple Intravenous Infusions of Umbilical Cord–derived MSCs in Patients with Heart Failure and Reduced Ejection Fraction) trial, published in Signal Transduction and Targeted Therapy, was a single-center, randomized, placebo-controlled study (ClinicalTrials.gov identifier: NCT04992832) that enrolled 40 patients.

The study evaluated three intravenous infusions of umbilical cord-derived MSCs (UC-MSCs) administered at six-week intervals. The primary safety endpoint was the incidence of serious adverse events (SAEs), and the primary efficacy endpoint was the change in left ventricular ejection fraction (LVEF). Secondary endpoints included changes in right ventricular (RV) end-systolic and end-diastolic volumes (ESV and EDV). Thirty-nine patients completed 12 study visits over a 360-day follow-up period or until death.

The incidence of SAEs did not differ significantly between the UC-MSC and placebo groups. Elevated D-dimer levels were observed in the UC-MSC group, with a negative correlation noted between D-dimer levels and LVEF. No significant difference in change in LVEF was observed between groups.

Improvement in change in RV end-systolic volume (RVESV) was greater in the UC-MSC group compared with placebo-treated patients (P = 0.033). Multi-dose UC-MSC infusions were administered without a difference in SAE incidence, with changes observed in RV volumes and D-dimer levels.