The PRoject of Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT IV) trial: Study rationale, design, and baseline patient characteristics

Alexander, John H.; Ferguson, T. Bruce; Joseph, Diane M.; Mack, Michael J.; Wolf, Randall K.; Gibson, C. Michael; Gennevois, Daniel; Lorenz, Todd J.; Harrington, Robert A.; Peterson, Eric D.; Lee, Kerry L.; Califf, Robert M.; Kouchoukos, Nicholas T.; PREVENT IV Investigators,

doi:10.1016/j.ahj.2005.05.021

« Previous Next »American Heart Journal
Volume 150, Issue 4 , Pages 643-649, October 2005

The PRoject of Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT IV) trial:

Study rationale, design, and baseline patient characteristics

John H. Alexander, MD, MS
- Duke University Medical Center, Duke Clinical Research Institute, Durham, NC
- Reprint requests: John H. Alexander, MD, MS, Box 3300, Duke University Medical Center, Duke Clinical Research Institute, Durham, NC, 27715.
T. Bruce Ferguson Jr., MD
- Louisiana State University, New Orleans, La
Diane M. Joseph, BS
- Duke University Medical Center, Duke Clinical Research Institute, Durham, NC
Michael J. Mack, MD
- Cardiopulmonary Research Science and Technology Institute, Dallas, Tex
Randall K. Wolf, MD
- University of Cincinnati, Cincinnati, Ohio
C. Michael Gibson, MD, MS
- PERFUSE Angiographic Laboratory, Beth Israel-Deaconess Medical Center, Boston, Mass
Daniel Gennevois, MD
- Corgentech Inc., South San Francisco, Calif
Todd J. Lorenz, MD
- Corgentech Inc., South San Francisco, Calif
Robert A. Harrington, MD
- Duke University Medical Center, Duke Clinical Research Institute, Durham, NC
Eric D. Peterson, MD, MPH
- Duke University Medical Center, Duke Clinical Research Institute, Durham, NC
Kerry L. Lee, PhD
- Duke University Medical Center, Duke Clinical Research Institute, Durham, NC
Robert M. Califf, MD
- Duke University Medical Center, Duke Clinical Research Institute, Durham, NC
Nicholas T. Kouchoukos, MD
- Missouri Baptist Medical Center, St. Louis, Mo
PREVENT IV Investigators

Received 27 February 2005; accepted 17 May 2005.

Background

Coronary artery bypass graft (CABG) surgery with autologous vein graft (VG) conduit is one of the most frequently performed operations in the United States. Unfortunately, many VGs become occluded during long-term follow-up largely because of neointimal hyperplasia. A novel approach to preventing neointimal hyperplasia is with the double-stranded oligonucleotide edifoligide (Corgentech Inc, South San Francisco, Calif). Edifoligide inhibits E2F, a transcription factor that activates cell-cycle genes responsible for neointimal hyperplasia.

Methods

PREVENT IV is a phase-III, multicenter, randomized double-blind placebo-controlled trial of ex vivo treatment of autologous VGs with edifoligide in patients undergoing initial CABG surgery. The primary end point is VG failure, defined as death or ≥75% stenosis in a treated VG at 12- to 18-month angiographic follow-up. Secondary end points include major adverse cardiac events through at least 5 years and adverse events through 30 days.

Results

Enrollment of 3014 patients from 107 sites was completed on October 22, 2003. The baseline and procedural characteristics of the PREVENT IV population are generally well matched to a contemporary population of patients undergoing initial CABG from the Society of Thoracic Surgeons National Database. Angiographic follow-up is ongoing and scheduled to be completed in March 2005.

Conclusions

The PREVENT IV data will establish whether VG pretreatment with an E2F transcription factor decoy, edifoligide, can improve graft patency and reduce the long-term morbidity and mortality of patients undergoing CABG surgery.