AIMS: Genes encoding vascular endothelial growth factor (VEGF) can potentially augment myocardial perfusion in patients with coronary artery disease (CAD). We conducted a randomised, double-blind, placebo-controlled gene therapy study with the adenovirus carrying VEGF121 (BIOBYPASS [AdGVVEGF121.10NH]). METHODS AND RESULTS:Seventeen patients with severe CAD were 2:1 randomised to BIOBYPASS (n=12; 61 years) or placebo (n=5; 64) as 12 intra-myocardial injections into the ischaemic area using the NOGA XP® system. The study was terminated prematurely due to a company product portfolio decision. Mean change in total exercise duration from baseline to 12, 26 and 52 weeks was 20.2, 21.4 and 16.4 sec in BIOBYPASS treated and 46.2, 31.4 and 12.4 sec in placebo (NS). Change from baseline to at least 1 mm ST depression during exercise at 12, 26 and 52 weeks did not differ between BIOBYPASS and placebo. Change in stress-induced ischaemia score was similar in the BIOBYPASS (3.4%) and placebo (2.0%) groups. An improvement in symptoms was seen in patients treated with BIOBYPASS, but no difference between the groups. CONCLUSIONS:Direct intramyocardial injection of BIOBYPASS (AdGVVEGF121.10NH) was safe but did not improve exercise capacity, time to ischaemic threshold or myocardial perfusion compared to sham injection in patients with refractory myocardial ischaemia.
RCT Entities:
AIMS: Genes encoding vascular endothelial growth factor (VEGF) can potentially augment myocardial perfusion in patients with coronary artery disease (CAD). We conducted a randomised, double-blind, placebo-controlled gene therapy study with the adenovirus carrying VEGF121 (BIOBYPASS [AdGVVEGF121.10NH]). METHODS AND RESULTS: Seventeen patients with severe CAD were 2:1 randomised to BIOBYPASS (n=12; 61 years) or placebo (n=5; 64) as 12 intra-myocardial injections into the ischaemic area using the NOGA XP® system. The study was terminated prematurely due to a company product portfolio decision. Mean change in total exercise duration from baseline to 12, 26 and 52 weeks was 20.2, 21.4 and 16.4 sec in BIOBYPASS treated and 46.2, 31.4 and 12.4 sec in placebo (NS). Change from baseline to at least 1 mm ST depression during exercise at 12, 26 and 52 weeks did not differ between BIOBYPASS and placebo. Change in stress-induced ischaemia score was similar in the BIOBYPASS (3.4%) and placebo (2.0%) groups. An improvement in symptoms was seen in patients treated with BIOBYPASS, but no difference between the groups. CONCLUSIONS: Direct intramyocardial injection of BIOBYPASS (AdGVVEGF121.10NH) was safe but did not improve exercise capacity, time to ischaemic threshold or myocardial perfusion compared to sham injection in patients with refractory myocardial ischaemia.
Authors: Zhi Hong Lu; Sergey Kaliberov; Jingzhu Zhang; Barbara Muz; Abdel K Azab; Rebecca E Sohn; Lyudmila Kaliberova; Yingqiu Du; David T Curiel; Jeffrey M Arbeit Journal: Lab Invest Date: 2014-06-23 Impact factor: 5.662