The RENEW Trial Efficacy and Safety of Intramyocardial Autologous CD34+ cell Administration in Patients With Refractory Angina

被引：103

作者：

Povsic, Thomas J. ^{[1
]}

Henry, Timothy D. ^{[2
]}

Traverse, Jay H. ^{[3
]}

Fortuin, F. David ^{[4
]}

Schaer, Gary L. ^{[5
]}

Kereiakes, Dean J. ^{[6
]}

Schatz, Richard A. ^{[7
]}

Zeiher, Andreas M. ^{[8
]}

White, Christopher J. ^{[9
]}

Stewart, Duncan J. ^{[10
]}

Jolicoeur, E. Marc ^{[11
]}

Bass, Theodore ^{[12
]}

Henderson, David A. ^{[13
]}

Dignacco, Patricia ^{[1
]}

Gu, Ziangoiong ^{[1
]}

Al-Khalidi, Hussein R. ^{[1
]}

Junge, Candice ^{[14
]}

Nada, Adel ^{[15
]}

Hunt, Andrea S. ^{[16
]}

Losordo, Douglas W. ^{[17
]}

机构：

[1] Duke Med, Duke Clin Res Inst, Durham, NC USA

[2] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

[3] Abbott NW Hosp, Minneapolis Heart Inst Fdn, Minneapolis, MN USA

[4] Mayo Clin Hosp, Phoenix, AZ USA

[5] Rush Univ, Med Ctr, Chicago, IL 60612 USA

[6] Christ Hosp, Heart & Vasc Ctr, Cincinnati, OH 45219 USA

[7] Scripps Clin Torrey Pines, La Jolla, CA USA

[8] Goethe Univ Frankfurt, Dept Med, Frankfurt, Germany

[9] Ochsner Med Ctr, New Orleans, LA USA

[10] Univ Ottawa, Ottawa Hosp, Res Inst, Quebec City, ON, Canada

[11] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada

[12] Univ Florida, Jacksonville Cardiovasc Ctr, Jacksonville, FL USA

[13] Cardiol Res Associates, Daytona Beach, FL USA

[14] Amgen Inc, Thousand Oaks, CA USA

[15] Intellia Therapeut Inc, Cambridge, MA USA

[16] Baxalta US Inc, Bannockburn, IL USA

[17] Caladrius Biosci, New York, NY USA

来源：

JACC-CARDIOVASCULAR INTERVENTIONS | 2016年 / 9卷 / 15期

关键词：

angina; angiogenesis; CD34(+); interventional therapy; progenitor cell; stable coronary disease; stem cell; LONG-TERM SURVIVAL; DOUBLE-BLIND; THERAPEUTIC NEOVASCULARIZATION; MYOCARDIAL-ISCHEMIA; PROGENITOR CELLS; MEDICAL-RESEARCH; REVASCULARIZATION; TRANSPLANTATION; RESPONSIBILITIES; METAANALYSIS;

D O I：

10.1016/j.jcin.2016.05.003

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVES 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. BACKGROUND IM administration of autologous CD34(+) cells has been associated consistently with improvements in functional capacity and angina symptoms in early phase clinical trials. METHODS 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. RESULTS 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(+)]). CONCLUSIONS 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) (C) 2016 by the American College of Cardiology Foundation.

引用

页码：1576 / 1585

页数：10

共 34 条

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