The PRIME-HFrEF trial was a single-center, randomized, placebo-controlled study assessing the safety and exploratory efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in patients with heart failure and reduced ejection fraction (HFrEF). Forty patients were enrolled, with 39 completing the 360-day follow-up. The primary safety endpoint was the incidence of serious adverse events (SAEs), which showed no significant difference between the UC-MSC and placebo groups. The primary efficacy endpoint was the change in left ventricular ejection fraction (LVEF), which did not differ significantly between groups. Secondary endpoints included changes in right ventricular end-systolic volume (RVESV) and end-diastolic volume (RVEDV). Notably, the UC-MSC group experienced a significant improvement in RVESV compared to placebo (P=0.033). Safety analysis revealed elevated D-dimer levels in the UC-MSC group, indicating increased coagulability, which correlated negatively with LVEF. These findings suggest that while UC-MSC infusions are safe and improve RV volumes, the associated increase in coagulability may limit potential benefits on left ventricular function. Clinicians should consider the balance between these effects when evaluating UC-MSC therapy for HFrEF.
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· Auto-published
This study involves patients with heart failure, a condition where the heart struggles to pump blood effectively. Researchers tested a treatment using stem cells from umbilical cords, giving patients three infusions over several weeks to see if it was safe and effective. They found that the treatment was mostly safe, with no major differences in serious side effects between those receiving the stem cells and those getting a placebo (a fake treatment). However, patients who received the stem cells showed higher levels of a substance that indicates increased blood clotting risk. While there were no significant improvements in heart function measured by one test, there was a noticeable improvement in another measure related to the right side of the heart. This suggests that the treatment might help some aspects of heart function. For patients, this could mean a new potential option for managing heart failure, but it’s important to be aware of the increased clotting risk. More research is needed to understand the long-term effects and benefits of this treatment.
What this means for you: Stem cell treatment for heart failure may help some heart function but carries a risk of increased blood clotting.
View Original Abstract ↓
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.