Table 2.
Clinical studies of gene targeting in Ischemic Heart Disease utilizing plasmid vectors
| Reference | Trial Design | Number of Patients | Therapeutic Agent | Delivery | Endpoints | Outcomes | Major Adverse Events |
|---|---|---|---|---|---|---|---|
| [46] | Phase I | 5 | VEGF-A165 | Intramyocardial injection—mini-thoracotomy | Myocardial perfusion (SPECT) | Improved | None |
| [47] | Phase I | 20 | VEGF-A165 | Intramyocardial injection—mini-thoracotomy | Myocardial perfusion (SPECT); Angina/week | Improved; Improved | Arrhythmia (n=1) |
| [39] | Phase I | 15 | VEGF | Intracoronary injection | Restenosis at 6 months | No change | None |
| [49] | Phase I/II | 6 | VEGF-A165 | Intramyocardial injection—mini-thoracotomy | Maximal systolic velocities; CCS class; NTG/week | Improved; Improved; Improved | None |
| [50] | Open-Label Study | 7 | VEGF-A165 | Intramyocardial injection—mini-thoracotomy | Myocardial perfusion; CCS class; NTG/week | Improved; Improved; Improved | None |
| [51] | Phase I | 30 | VEGF-A2 | Intramyocardial injection—mini-thoracotomy | CCS; Angina/week; NTG/week | Improved; Improved; Improved | Death (n=1) |
| [35] | Pre-clinical | 6 | VEGF-A2 | NOGA—percutaneous endocardial injections | Myocardial perfusion (NOGA and SPECT) | Improved; Improved | None |
| [52] | PhaseI/II— RCT | 27 | VEGF-A2 | NOGA—percutaneous endocardial injections | Myocardial perfusion (NOGA and SPECT); CCS | Improved and Improvement trend; improved | CVA (n=2, placebo group) |
| [53] | Euroinject One Phase II | 80 | VEGF-A165 | NOGA—percutaneous endocardial injections | Myocardial perfusion (NOGA and SPECT); Regional wall motion; CCS; Angina/week | No change; Improved; Improved; Improved; No change | Cardiac tamponade (n=1), 3rd degree AV block (n=1), MI (n=1) |
| [54] | Phase I | VEGF-A165 | NOGA—percutaneous endocardial injections | Myocardial perfusion (SPECT and MRI); EDV (MRI); ESV (MRI) | No change and no change; No change; Improved | Death (n=1), MI (n=2) | |
| [55] | NORTHERN Phase II/III | 93 | VEGF-A165 | NOGA—percutaneous endocardial injections | Myocardial perfusion (SPECT); CCS | No change; Improved | Death (n=2), MI (n=6) |
VEGF, vascular endothelial growth factor; SPECT, single photon emission computerized tomography; CCS, Canadian Cardiovascular Society functional classification of angina; NTG, nitroglycerine tablets; NOGA, non-fluoroscopic electromechanical mapping; RCT, randomized controlled trial; CVA, cerebrovascular accident; MI, myocardial infarction; MRI, magnetic resonance imaging; EDV, end diastolic volume; ESV, end systolic volume