Journal of Clinical Trials
Open Access

Abstract

Safety and Efficacy of Intracoronary Ad-HGF Administration for Treating Severe Coronary Disease: Results From Long-Term Follow-Up of a Phase I Clinical Trial

Haoyu Meng, Yingqiang Du, Bo Chen, Mohammad Bilaal Toorabally, Ze-Mu Wang, Ningtian Zhou, Zhihui Xu, Dingguo Zhang, Zhengxian Tao, Liansheng Wang, Qingzhe Jia and Zhijian Yang

Objective: This study is a long-term follow-up of our previous phase I clinical trial and aims at evaluating the long-term safety and efficacy of intracoronary Ad-HGF administration for treating coronary disease.

Methods: This study includes 22 patients (11 in the experiment group and 11 in the control group) with diffused and severe coronary disease who had received the optimal standardized medication therapy and was not amenable to revascularization. Intracoronary Ad-HGF gene transfer was administered to the distal part of the accessible artery by over-the wire balloon or at the ostium of the target vessels by diagnostic coronary catheter in the experiment group. Safety parameters were measured and compared between baseline and follow-ups (5-week; 12-month; 36- month) only in the experiment group. The changes of efficacy parameters (ejection fraction, EF) from baseline to 36- month follow-up (δEF) were measured in both groups and compared with each other.

Results: This study confirmed the long-term safety of intracoronary Ad-HGF administration for treating severe diffuse coronary disease. All the eleven patients of the experiment group were alive after 36-months follow-up. During the follow-up, no new-onset arrhythmia was recorded; no malignant tumor was diagnosed; no paroxysmal or long-term fever was recorded; no retinal vascular anomaly was diagnosed. There were no statistically significant differences between the follow-ups and baseline in regard to blood parameters, including WBC, Hb, ALT, AST, BUN, Cr, CEA and AFP. In addition, intracoronary Ad-HGF efficiently improved echocardiographic EF at the 36-month follow-up compared to baseline (F=4.4, p=0.024) and with the control group (δEF: 3.5 ± 1.1 vs. -4.5 ± 1.3, MD: 8, p=0.0001). The medium-high dose subgroup also showed higher ECT-EF at the 36-month follow-up than baseline (MD: 4.8, p=0.017, n=8) and higher improvement of ECT-EF than the control group (δEF: 4.8 ± 1.5 vs. 0.3 ± 1.7, MD: 4.5, p=0.08).

Conclusion: Intracoronary Ad-HGF administration is safe and potentially efficient in improving EF of patients with severe diffuse coronary disease in 3-year follow-up.