title: A randomized, double-blind, placebo-controlled, multicenter, pilot study of the safety and feasibility of catheter-based intramyocardial injection of AdVEGF121 in patients with refractory advanced coronary artery disease.
abstract: BACKGROUND
  The experience with direct myocardial injection of adenovirus encoding angiogenic growth factor is limited to invasive surgical approach. Accordingly, we sought to evaluate, for the first time, in a randomized, double-blind, placebo-controlled, phase I pilot study the safety and feasibility of percutaneous catheter-based intramyocardial delivery of a replication-deficient adenovector encoding the 121-amino-acid isoform of vascular endothelial growth factor (AdVEGF121).
  
  
  METHODS
  Ten "no-option" patients with severe coronary artery disease were randomized (2:1) to receive AdVEGF121 (4 x 10(10) pu) or placebo as fifteen 100 microL, evenly distributed, endomyocardial injections using a nonflouroscopic, 3-dimensional mapping and injection (NOGA) catheter-based system.
  
  
  RESULTS
  Injection procedure was successfully completed in all cases and was associated with no major adverse events. AdVEGF121 was considered potentially associated with a single serious adverse event of transient moderate fever. Elevated postprocedure CK and CK-MB fraction levels were recorded in two placebo-treated and three AdVEGF121-treated patients; all CK measured values were <1.5 times upper limit of normal. All adenoviral cultures (urine and throat swab) were negative 24-hr after dosing, and no significant changes in serial plasma VEGF levels were noted over time. At 12 months follow-up, no cancers, proliferative retinal changes, or significant abnormalities in hepatic, renal or hematological indices were observed.
  
  
  CONCLUSIONS
  Percutaneous, catheter-based AdVEGF121 intramyocardial injection is a practical, feasible, and potentially safe approach for intramyocardial gene transfer. A larger randomized, phase II efficacy study is warranted.
authors.affiliation: Cardiology Department, Rabin Medical Center, Petach-Tikva, Israel. shmuelf@clalit.org.il
authors.forename: Shmuel
authors.initials: S
authors.lastname: Fuchs
authors.forename: Nabil
authors.initials: N
authors.lastname: Dib
authors.forename: Barry M
authors.initials: BM
authors.lastname: Cohen
authors.forename: Petros
authors.initials: P
authors.lastname: Okubagzi
authors.forename: Edward B
authors.initials: EB
authors.lastname: Diethrich
authors.forename: Ann
authors.initials: A
authors.lastname: Campbell
authors.forename: Jennifer
authors.initials: J
authors.lastname: Macko
authors.forename: Paul D
authors.initials: PD
authors.lastname: Kessler
authors.forename: Henrik S
authors.initials: HS
authors.lastname: Rasmussen
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Epstein
authors.forename: Ran
authors.initials: R
authors.lastname: Kornowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000787:Angina Pectoris / Q000188:drug therapy; D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood / Q000652:urine; D006328:Cardiac Catheterization; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D052279:Creatine Kinase, MB Form / Q000097:blood / Q000187:drug effects; D004311:Double-Blind Method; D017079:Exercise Tolerance; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007267:Injections / Q000379:methods; D008297:Male; D008875:Middle Aged; D009206:Myocardium; D010807:Physical Endurance; D010865:Pilot Projects; D011788:Quality of Life; D013997:Time Factors; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000187:drug effects
chemical_list: D043925:Angiogenesis Inducing Agents; D015415:Biomarkers; D020107:Troponin T; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D052279:Creatine Kinase, MB Form