The VIVA trial: Vascular endothelial growth factor in ischemia for vascular angiogenesis

Timothy D. Henry, Brian H. Annex, George R. McKendall, Michael A. Azrin, John J. Lopez, Frank J. Giordano, P. K. Shah, James T. Willerson, Raymond L. Benza, Daniel S. Berman, C. Michael Gibson, Alex Bajamonde, Amy Chen Rundle, Jennifer Fine, Edward R. McCluskey

Research output: Contribution to journalArticle

Abstract

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. Methods and Results - A total of 178 patients with stable exertional angina, unsuitable for standard revascularization, were randomized to receive placebo, low-dose rhVEGF (17 ng · kg-1 · min-1, or high-dose rhVEGF (50 ng · kg-1 · 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.

Original languageEnglish (US)
Pages (from-to)1359-1365
Number of pages7
JournalCirculation
Volume107
Issue number10
DOIs
StatePublished - Mar 18 2003
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor A
Blood Vessels
Exercise Test
Ischemia
Placebos
Proteins
Intravenous Infusions
Quality of Life
human VEGFA protein
Clinical Trials, Phase I
Myocardial Perfusion Imaging
Stable Angina
Animal Models
Safety

Keywords

  • Angina
  • Angiogenesis
  • Growth substances
  • Heart disease
  • Ischemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Henry, T. D., Annex, B. H., McKendall, G. R., Azrin, M. A., Lopez, J. J., Giordano, F. J., ... McCluskey, E. R. (2003). The VIVA trial: Vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation, 107(10), 1359-1365. https://doi.org/10.1161/01.CIR.0000061911.47710.8A

The VIVA trial : Vascular endothelial growth factor in ischemia for vascular angiogenesis. / Henry, Timothy D.; Annex, Brian H.; McKendall, George R.; Azrin, Michael A.; Lopez, John J.; Giordano, Frank J.; Shah, P. K.; Willerson, James T.; Benza, Raymond L.; Berman, Daniel S.; Gibson, C. Michael; Bajamonde, Alex; Rundle, Amy Chen; Fine, Jennifer; McCluskey, Edward R.

In: Circulation, Vol. 107, No. 10, 18.03.2003, p. 1359-1365.

Research output: Contribution to journalArticle

Henry, TD, Annex, BH, McKendall, GR, Azrin, MA, Lopez, JJ, Giordano, FJ, Shah, PK, Willerson, JT, Benza, RL, Berman, DS, Gibson, CM, Bajamonde, A, Rundle, AC, Fine, J & McCluskey, ER 2003, 'The VIVA trial: Vascular endothelial growth factor in ischemia for vascular angiogenesis', Circulation, vol. 107, no. 10, pp. 1359-1365. https://doi.org/10.1161/01.CIR.0000061911.47710.8A
Henry TD, Annex BH, McKendall GR, Azrin MA, Lopez JJ, Giordano FJ et al. The VIVA trial: Vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation. 2003 Mar 18;107(10):1359-1365. https://doi.org/10.1161/01.CIR.0000061911.47710.8A
Henry, Timothy D. ; Annex, Brian H. ; McKendall, George R. ; Azrin, Michael A. ; Lopez, John J. ; Giordano, Frank J. ; Shah, P. K. ; Willerson, James T. ; Benza, Raymond L. ; Berman, Daniel S. ; Gibson, C. Michael ; Bajamonde, Alex ; Rundle, Amy Chen ; Fine, Jennifer ; McCluskey, Edward R. / The VIVA trial : Vascular endothelial growth factor in ischemia for vascular angiogenesis. In: Circulation. 2003 ; Vol. 107, No. 10. pp. 1359-1365.
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AU - Annex, Brian H.

AU - McKendall, George R.

AU - Azrin, Michael A.

AU - Lopez, John J.

AU - Giordano, Frank J.

AU - Shah, P. K.

AU - Willerson, James T.

AU - Benza, Raymond L.

AU - Berman, Daniel S.

AU - Gibson, C. Michael

AU - Bajamonde, Alex

AU - Rundle, Amy Chen

AU - Fine, Jennifer

AU - McCluskey, Edward R.

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N2 - 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. Methods and Results - A total of 178 patients with stable exertional angina, unsuitable for standard revascularization, were randomized to receive placebo, low-dose rhVEGF (17 ng · kg-1 · min-1, or high-dose rhVEGF (50 ng · kg-1 · 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.

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KW - Growth substances

KW - Heart disease

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