The VIVA trial: Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis.
BACKGROUND
Recombinant human vascular endothelial growth factor protein (rhVEGF) stimulates angiogenesis in animal models and was well tolerated in Phase I clinical trials. VIVA (Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis) is a double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of intracoronary and intravenous infusions of rhVEGF.


RESULTS
A total of 178 patients with stable exertional angina, unsuitable for standard revascularization, were randomized to receive placebo, low-dose rhVEGF (17 ng x kg(-1) x min(-1)), or high-dose rhVEGF (50 ng x kg(-1) x min(-1)) by intracoronary infusion on day 0, followed by intravenous infusions on days 3, 6, and 9. Exercise treadmill tests, angina class, and quality of life assessments were performed at baseline, day 60, and day 120. Myocardial perfusion imaging was performed at baseline and day 60. At day 60, the change in exercise treadmill test (ETT) time from baseline was not different between groups (placebo, +48 seconds; low dose, +30 seconds; high dose, +30 seconds). Angina class and quality of life were significantly improved within each group, with no difference between groups. By day 120, placebo-treated patients demonstrated reduced benefit in all three measures, with no significant difference compared with low-dose rhVEGF. In contrast, high-dose rhVEGF resulted in significant improvement in angina class (P=0.05) and nonsignificant trends in ETT time (P=0.15) and angina frequency (P=0.09) as compared with placebo.


CONCLUSIONS
rhVEGF seems to be safe and well tolerated. rhVEGF offered no improvement beyond placebo in all measurements by day 60. By day 120, high-dose rhVEGF resulted in significant improvement in angina and favorable trends in ETT time and angina frequency.
Henry
Timothy D
TD
Division of Cardiology at Hennepin County Medical Center and University of Minnesota, Minneapolis, USA. henry003@tc.umn.edu
Annex
Brian H
BH
McKendall
George R
GR
Azrin
Michael A
MA
Lopez
John J
JJ
Giordano
Frank J
FJ
Shah
P K
PK
Willerson
James T
JT
Benza
Raymond L
RL
Berman
Daniel S
DS
Gibson
C Michael
CM
Bajamonde
Alex
A
Rundle
Amy Chen
AC
Fine
Jennifer
J
McCluskey
Edward R
ER
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000145:classification; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000187:drug effects / Q000254:growth & development; D004311:Double-Blind Method; D016228:Endothelial Growth Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005080:Exercise Test; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008222:Lymphokines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011788:Quality of Life; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors