What is the problem/issue being addressed?
The most common symptom of coronary heart disease (CHD) is angina, chest pain, and within this group of patients refractory angina constitutes a serious clinical problem. The European Society of Cardiology has emphasised this important clinical problem and defined refractory angina as a chronic condition (> 3 months) characterised by the presence of angina caused by coronary insufficiency due to coronary artery disease which cannot be controlled by a combination of medical therapy, angioplasty and coronary bypass. Despite the fact that better treatment methods have been developed for CHD patients in general, this group of patients suffer from significant symptoms and disability even with maximal medication. Thus, there is a significant unmet clinical need to develop new therapies for this rapidly increasing group of patients whose annual mortality is less than 4%.
Why is it important for society?
Patients with refractory angina usually have severely compromised quality of life leading to impaired ability to work and to perform physical activities including exercise and rehabilitation programs, both of which have been shown to improve the outcome. Refractory angina, due to its chronic nature, is also a psychological stressor further impairing the general health status. The economic burden imposed on the healthcare system as well as on the patients is high. Due to relatively low mortality these patients will require long-term treatment, including medical therapy and repeated use of devices, which means substantial costs for both patients and healthcare systems.
What are the overall objectives?
The aim of this study is to evaluate in a randomized, placebo-controlled, double-blinded, multicentre phase II study at 6 centres in the EU, the efficacy, proof-of-concept and safety of a new targeted approach based on the catheter-delivered endocardial adenovirus-mediated regenerative vascular endothelial growth factor-D (AdVEGF-D) gene transfer in 180 patients with severe CHD for whom revascularisation cannot be performed.
• Our primary objective is to demonstrate the efficacy of the gene therapy to improve exercise capacity and relief of angina pectoris symptoms 6 months after the treatment, as measured by a 6-minute walking test.
• As our secondary objective we will demonstrate the efficacy of the gene transfer to increase myocardial perfusion assessed with PET imaging at 6 months.
If successful, this trial will give proof of concept and clinical validation for this new percutaneous, cost-efficient, innovative state-of-the-art regenerative therapy for the rapidly growing group of refractory angina patients.
As the recruitment of patients continued up until the end of the project it has not been possible to draw any conclusions yet, these will come when the data are unblinded once all patients have undergone their 12 month follow up.
