The PRoject of Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT IV) trial: study rationale, design, and baseline patient characteristics.
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 > 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.
Alexander
John H
JH
Duke University Medical Center, Duke Clinical Research Institute, Durham, NC 27715, USA. john.h.alexander@duke.edu
Ferguson
T Bruce
TB
Joseph
Diane M
DM
Mack
Michael J
MJ
Wolf
Randall K
RK
Gibson
C Michael
CM
Gennevois
Daniel
D
Lorenz
Todd J
TJ
Harrington
Robert A
RA
Peterson
Eric D
ED
Lee
Kerry L
KL
Califf
Robert M
RM
Kouchoukos
Nicholas T
NT
D000368:Aged; D001026:Coronary Artery Bypass / Q000009:adverse effects / Q000379:methods*; D004247:DNA / Q000627:therapeutic use*; D004867:Equipment Design; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006965:Hyperplasia / Q000517:prevention & control; D007275:Injections, Intravenous / Q000295:instrumentation; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009841:Oligonucleotides; D011183:Postoperative Complications / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D017539:Tunica Intima / Q000473:pathology
D009841:Oligonucleotides; C502518:edifoligide; D004247:DNA