title: The RENEW Trial: Efficacy and Safety of Intramyocardial Autologous CD34(+) Cell Administration in Patients With Refractory Angina.
abstract: This study tested whether intramyocardial (IM) administration of mobilized, purified autologous CD34(+) cells would improve total exercise time (TET) and angina frequency in patients with refractory angina.
  
  
  
  IM administration of autologous CD34(+) cells has been associated consistently with improvements in functional capacity and angina symptoms in early phase clinical trials.
  
  
  
  RENEW (Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34+ Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina) was a randomized, double-blind, multicenter trial comparing IM CD34(+) administration with no intervention (open-label standard of care) or IM placebo injections (active control). The primary efficacy endpoint was change in TET at 12 months. Key secondary endpoints include changes in angina frequency at 3, 6, and 12 months, and TET at 3 and 6 months. The key safety analysis was the incidence of major adverse cardiovascular events through 24 months.
  
  
  
  The sponsor terminated the study for strategic considerations after enrollment of 112 of planned 444 patients. The difference in TET between patients treated with cell therapy versus placebo was 61.0 s at 3 months (95% confidence interval (CI): -2.9 to 124.8; p = 0.06), 46.2 s at 6 months (95% CI: -28.0 to 120.4; p = 0.22), and 36.6 s at 12 months (95% CI: -56.1 to 129.2; p = 0.43); angina frequency was improved at 6 months (relative risk: 0.63; p = 0.05). Autologous CD34(+) cell therapy seemed to be safe compared with both open-label standard of care and active control (major adverse cardiovascular events 67.9% [standard of care], 42.9% (active control), 46.0% [CD34(+)]).
  
  
  
  Due to early termination, RENEW was an incomplete experiment; however, the results were consistent with observations from earlier phase studies. These findings underscore the need for a definitive trial. (Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34(+) Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina [RENEW]: NCT01508910).
authors: Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina. Electronic address: povsi001@mc.duke.edu.
authors: Thomas J
authors: TJ
authors: Povsic
authors: Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Timothy D
authors: TD
authors: Henry
authors: Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, Minnesota.
authors: Jay H
authors: JH
authors: Traverse
authors: Mayo Clinic Hospital, Phoenix, Arizona.
authors: F David
authors: FD
authors: Fortuin
authors: Rush University Medical Center, Chicago, Illinois.
authors: Gary L
authors: GL
authors: Schaer
authors: The Christ Hospital Heart and Vascular Center, Cincinnati, Ohio.
authors: Dean J
authors: DJ
authors: Kereiakes
authors: Scripps Clinic Torrey Pines, La Jolla, California.
authors: Richard A
authors: RA
authors: Schatz
authors: Department of Medicine, University of Frankfurt, Frankfurt, Germany.
authors: Andreas M
authors: AM
authors: Zeiher
authors: Ochsner Medical Center, New Orleans, Louisiana.
authors: Christopher J
authors: CJ
authors: White
authors: Ottawa Hospital Research Institute, University of Ottawa, Quebec, Ontario, Canada.
authors: Duncan J
authors: DJ
authors: Stewart
authors: Montreal Heart Institute, Université de Montréal, Montréal, Quebec, Canada.
authors: E Marc
authors: EM
authors: Jolicoeur
authors: University of Florida, Jacksonville Cardiovascular Center Jacksonville, Florida.
authors: Theodore
authors: T
authors: Bass
authors: Cardiology Research Associates, Daytona Beach, Florida.
authors: David A
authors: DA
authors: Henderson
authors: Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina.
authors: Patricia
authors: P
authors: Dignacco
authors: Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina.
authors: Ziangoiong
authors: Z
authors: Gu
authors: Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina.
authors: Hussein R
authors: HR
authors: Al-Khalidi
authors: Amgen Inc. Thousand Oaks, California.
authors: Candice
authors: C
authors: Junge
authors: Intellia Therapeutics, Inc., Cambridge, Massachusetts.
authors: Adel
authors: A
authors: Nada
authors: Baxalta US Inc., Bannockburn, Illinois.
authors: Andrea S
authors: AS
authors: Hunt
authors: Caladrius Biosciences, New York, New York.
authors: Douglas W
authors: DW
authors: Losordo
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D018952:Antigens, CD34 / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D066026:Endothelial Progenitor Cells / Q000378:metabolism / Q000637:transplantation*; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D020127:Recovery of Function; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014481:United States
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers
keywords: CD34(+); angina; angiogenesis; interventional therapy; progenitor cell; stable coronary disease; stem cell