A randomised, double-blind, placebo-controlled, multicentre study of the safety and efficacy of BIOBYPASS (AdGVVEGF121.10NH) gene therapy in patients with refractory advanced coronary artery disease: the NOVA trial.
OBJECTIVE
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]).


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.
The Heart Center, University Hospital Rigshospitalet, Copenhagen, Denmark. jens.kastrup@rh.regionh.dk
Jens
J
Kastrup
Erik
E
Jørgensen
Shmuel
S
Fuchs
Sigrid
S
Nikol
Hans Erik
HE
Bøtker
Mariann
M
Gyöngyösi
Dietmar
D
Glogar
Ran
R
Kornowski
D000256:Adenoviridae; D000368:Aged; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D004311:Double-Blind Method; D017079:Exercise Tolerance; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D009206:Myocardium; D015899:Tomography, Emission-Computed, Single-Photon; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000235:genetics*; D016277:Ventricular Function, Left
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A