PRIME-HFrEF Trial: a randomized, double-blind, multi-dose umbilical cord-derived mesenchymal stem cell regimen for heart failure
Summary
The safety of multi-dose mesenchymal stem cell (MSC) regimens has seldom been systematically investigated. 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 was a single-center, randomized, placebo-controlled, investigator-initiated study (ClinicalTrials.gov identifier: NCT04992832) that enrolled 40 patients. The trial aimed to evaluate the safety of t
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# PRIME-HFrEF Trial: a randomized, double-blind, multi-dose umbilical cord-derived mesenchymal stem cell regimen for heart failure
*Published: 2026 Mar 26*
The safety of multi-dose mesenchymal stem cell (MSC) regimens has seldom been
systematically investigated. 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 was a
single-center, randomized, placebo-controlled, investigator-initiated study
(ClinicalTrials.gov identifier: NCT04992832) that enrolled 40 patients. The
trial aimed to evaluate the safety of three intravenous infusions of Umbilical
Cord-derived MSCs (UC-MSCs) administered at six-week intervals in patients with
heart failure and reduced ejection fraction (HFrEF), while also collecting
exploratory efficacy data. The primary safety endpoint was the incidence of
serious adverse events (SAEs), and the primary efficacy endpoint was the change
(Δ) in left ventricular ejection fraction (LVEF). Secondary efficacy 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 treatment groups. However, UC-MSC-treated patients
exhibited elevated D-dimer levels, suggesting a treatment-associated increase in
coagulability. D-dimer levels were negatively correlated with LVEF, and no
significant difference in ΔLVEF was observed between groups. In contrast, the
improvement in ΔRVESV was significantly greater in the UC-MSC group than in
placebo-treated patients (P = 0.033). In summary, multi-dose UC-MSC infusions
were safely administered to patients with HFrEF and were associated with
improvements in RV volumes. However, these benefits were accompanied by
transient increases in coagulability, which may have attenuated potential
improvements in left ventricular contractile function.
DOI: 10.1038/s41392-026-02678-5