Randomised, double-blinded, placebo-controlled trial to assess the effects of intramyocardial bone-marrow-derived immunoselected CD133+ cells on left ventricle perfusion and function assessed by single-photon emission CT and MRI in patients with inducible ischaemia and refractory angina (REGENT-VSEL)

AIMS: REGENT‐VSEL (NCT01660581) is a randomised, double‐blinded, placebo‐controlled trial of intramyocardial (IM) autologous bone marrow (BM)‐derived CD133+ cells on left ventricle (LV) perfusion/function and clinical status. METHODS AND RESULTS: Inclusion criteria: stable angina (CCS II‐IV) despite maximum pharmacotherapy for at least two weeks since last medications change, ≥1 myocardial segment with inducible ischaemia in Tc‐99m SPECT with adenosine, no option of revascularisation by Heart Team, age >18 and <75 years. Exclusion criteria: acute coronary syndrome <6 months, NYHA III‐IV heart failure, LVEF <35%, intracardiac thrombus, severe aortic stenosis, ICD/CRT, bleeding diathesis, renal insufficiency (GFR <30 mL/min/1.73m2), pregnancy or lactation. Cells were harvested from 100 cc of BM aspirated from iliac crest in a GMP facility with immuno‐magnetic beads (CliniMACS; Miltenyi Biotec). Cardiology team was fully blinded to the group allocation. Cells or placebo were injected using the NOGA system (BDS) in predefined hibernating (unipolar voltage ≥6.0 mV with reduced LLS) areas of myocardium. Clinical evaluation and safety profile are monitored during scheduled outpatient visits: 1, 4, 6, and 12 months after hospital discharge. The primary endpoint was the change in myocardial perfusion 4 months after the procedure by 99m‐Tc SPECT with adenosine. The secondary endpoint was (1) global and segmental contractility by cardiac MRI, (2) exercise treadmill test (TET, ESTD, TTLA), (3) angina severity (CCS class), the frequency of nitrates intake, and (4) quality of life (Seattle Angina Questionnaire, SF36). Thirty‐one patients (23 males, mean LVEF 55.4%, 12 with diabetes, 23 previous PCI, 25 previous CABG, 21 previous MI) were randomised (1:1) to receive IM cell injections or placebo. Sixteen patients were randomised to the cell group and 15 received placebo (6‐16 injections of 0.2 mL). All patients completed IM procedures without any SAE. There were no deaths during the follow‐up. The last patient is scheduled for the 4‐month SPECT follow‐up in January 2016. CONCLUSIONS: The final results of primary and secondary endpoints will be presented.