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    
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.
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
Related Documents :
16337208 - Baseline echocardiographic characteristics of heart failure patients enrolled in a larg...
12798428 - Aldosterone receptor blockade improves left ventricular remodeling and increases ventri...
6641248 - Left ventricular function and extent of coronary artery disease in the absence of antec...
19477388 - Left ventricular systolic function is abnormal in diastolic heart failure: re-assessmen...
9737478 - Low-molecular-weight heparins in coronary stenting (the entices trial). enoxaparin and ...
19520378 - Left bundle-branch block with right axis deviation--a unique aberrancy during supravent...
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    
Division of Cardiology, Tufts School of Medicine/St Elizabeth's Medical Center, Boston, Mass 02135, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Angina Pectoris / diagnosis,  radionuclide imaging,  therapy
Body Surface Potential Mapping
Chronic Disease
Double-Blind Method
Endothelial Growth Factors / genetics*
Exercise Test
Gene Therapy* / adverse effects
Heart Ventricles*
Lymphokines / genetics*
Middle Aged
Myocardial Ischemia / diagnosis,  radionuclide imaging,  therapy*
Tomography, Emission-Computed, Single-Photon
Treatment Outcome
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
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

Previous Document:  Mechanisms controlling cell cycle arrest and induction of apoptosis after 12-lipoxygenase inhibition...
Next Document:  Elevated C-reactive protein values and atherosclerosis in sudden coronary death: association with di...