Document Detail


Phase 1/2 placebo-controlled, double-blind, dose-escalating trial of myocardial vascular endothelial growth factor 2 gene transfer by catheter delivery in patients with chronic myocardial ischemia.
MedLine Citation:
PMID:  11980678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: This phase 1/2 study investigated the safety of percutaneous catheter-based gene transfer of naked plasmid DNA encoding for vascular endothelial growth factor 2 (phVEGF2) to left ventricular (LV) myocardium in a prospective, randomized, double-blind, placebo-controlled, dose-escalating study of inoperable patients with class III or IV angina. METHODS AND RESULTS: A steerable deflectable 8F catheter with a 27-gauge needle at its distal tip was advanced percutaneously to the endocardial surface of the LV in 19 patients (age, 61+/-2 years) with chronic myocardial ischemia who were not candidates for conventional revascularization. Patients were randomized in a double-blind fashion to receive 6 injections (total volume, 6.0 mL) of placebo or phVEGF2 in doses of 200 microg (n=9), 800 microg (n=9), or 2000 microg (n=1) guided by LV electromechanical (NOGA) mapping with a gene-to-placebo ratio of 2:1. A total of 114 LV injections were delivered and caused no hemodynamic alterations, sustained ventricular arrhythmias, ECG evidence of infarction, or ventricular perforation. End-point analysis at 12 weeks disclosed a statistically significant improvement in Canadian Cardiovascular Society (CCS) angina class in phVEGF2-treated versus placebo-treated patients (-1.3 versus -0.1, P=0.04). Remaining efficacy end points--including change in exercise duration (91.8 versus 3.9 seconds), functional improvement by > or =2 CCS classes (9 of 12 versus 1 of 6), and Seattle Angina Questionnaire data--all showed strong trends favoring efficacy of phVEGF2 versus placebo treatment. CONCLUSIONS: This phase 1/2, double-blind, randomized trial provides preliminary data that support safety of phVEGF2 catheter-mediated myocardial gene transfer. The statistically significant reduction in anginal class and strong positive trends for remaining end points suggest that a larger phase 2/3 trial is warranted.
Authors:
Douglas W Losordo; Peter R Vale; Robert C Hendel; Charles E Milliken; F David Fortuin; Nancie Cummings; Richard A Schatz; Takayuki Asahara; Jeffrey M Isner; Richard E Kuntz
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Publication Detail:
Type:  Clinical Trial; Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  105     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-04-30     Completed Date:  2002-05-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2012-8     Citation Subset:  AIM; IM    
Affiliation:
Division of Cardiology, Tufts School of Medicine/St Elizabeth's Medical Center, Boston, Mass 02135, USA. douglas.losordo@tufts.edu
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MeSH Terms
Descriptor/Qualifier:
Angina Pectoris / diagnosis,  radionuclide imaging,  therapy
Body Surface Potential Mapping
Catheterization
Chronic Disease
Double-Blind Method
Endothelial Growth Factors / genetics*
Exercise Test
Female
Gene Therapy* / adverse effects
Heart Ventricles*
Humans
Lymphokines / genetics*
Male
Middle Aged
Myocardial Ischemia / diagnosis,  radionuclide imaging,  therapy*
Tomography, Emission-Computed, Single-Photon
Treatment Outcome
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Chemical
Reg. No./Substance:
0/Endothelial Growth Factors; 0/Lymphokines; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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