title: A phase 3, randomized, double-blinded, active-controlled, unblinded standard of care study assessing the efficacy and safety of intramyocardial autologous CD34+ cell administration in patients with refractory angina: design of the RENEW study.
abstract: Preclinical trials indicate that CD34+ cells represent an effective angiogenic stem cell component. Early-phase clinical trials suggest that intramyocardial administration of autologous CD34+ cells may improve functional capacity and symptoms of angina. RENEW is a pivotal phase 3 trial designed to determine the efficacy of granulocyte colony-stimulating factor (G-CSF)-mobilized CD34+ stem cells for the treatment for patients with refractory angina and chronic myocardial ischemia. Patients (n = 444) receiving maximally tolerated antianginal therapies and lacking conventional revascularization options with Canadian Cardiovascular Society class III or IV angina and ischemia on stress testing will be randomized 2:1:1 to cell therapy (G-CSF-mediated stem cell mobilization, apheresis, and intramyocardial injection of 1 × 10(5) autologous CD34(+) cells/kg), active control (G-CSF-mediated stem cell mobilization, apheresis, and intramyocardial placebo injection), or open-label standard of care. The primary efficacy end point is change in exercise treadmill time in the treated vs active control patients, with 90% power to detect a 60-second difference in exercise time between cell-treated (n = 200) and active control (n = 100) patients. Key secondary end points include total number of anginal episodes per week and the incidence of independently adjudicated major adverse cardiac events and serious adverse events. RENEW will be the first adequately powered study aimed at definitively determining the efficacy of a cell therapy (intramyocardially delivered autologous CD34+ cells) for improvement of functional capacity in patients with refractory angina.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA. thomas.povsic@duke.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Povsic
authors.forename: Candice
authors.initials: C
authors.lastname: Junge
authors.forename: Adel
authors.initials: A
authors.lastname: Nada
authors.forename: Richard A
authors.initials: RA
authors.lastname: Schatz
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Davidson
authors.forename: F David
authors.initials: FD
authors.lastname: Fortuin
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Kereiakes
authors.forename: Farrell O
authors.initials: FO
authors.lastname: Mendelsohn
authors.forename: Warren
authors.initials: W
authors.lastname: Sherman
authors.forename: Gary L
authors.initials: GL
authors.lastname: Schaer
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: White
authors.forename: Duncan
authors.initials: D
authors.lastname: Stewart
authors.forename: Kenneth
authors.initials: K
authors.lastname: Story
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Losordo
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060050:Angina, Stable / Q000175:diagnosis / Q000276:immunology / Q000601:surgery*; D018952:Antigens, CD34 / Q000276:immunology*; D004311:Double-Blind Method; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D009206:Myocardium; D011446:Prospective Studies; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000276:immunology*; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018952:Antigens, CD34