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DOI: 10.1055/s-2008-1037983
Intramyocardial transfection with hypoxia inducible factor-1 alpha via an adenoviral vector during coronary artery bypass grafting – results of the phase I multi centre study
Introduction: There are increasing numbers of patients who have advanced coronary artery disease (CAD) with limited percutaneous and/or surgical options for revascularization of ischemic cardiac muscle. We performed a prospective, randomized, double-blinded Phase I multicenter clinical trial to assess the feasibility and preliminary safety of delivering a multivalent, pro-angiogenic transcription factor termed „Hypoxia Inducible Factor-1 alpha“ (HIF-1a), delivered to ischemic cardiac muscle via a type 2 adenoviral vector (Genzyme Europe B.V., Netherlands).
Methods: Thirteen patients were included on the basis of the following two criteria: 1) At least one hypoperfused area of viable ventricular muscle without options for revascularization (as determined by SPECT and coronary angiography), 2): LVEF ≥30%. After CABG grafting was completed, 10 injections of 0.1ml of the study drug (n=10), in three escalating doses (1×1010, 3×1010 or 1×1011 viral particles) or saline (n=3) as a placebo control, were injected intramyocardially.
Results: At an average follow-up of 39 months, all patients had uncomplicated postoperative courses, were alive and doing well. One patient had a clinically asymptomatic, self-limited run of tachycardia at 3 weeks post-operatively. At 6 months, one patient developed recurrent angina. PET revealed improvement in perfusion in the HIF-1a injected areas in selected patients. The potential for a contribution to improved perfusion from neighboring grafted areas can not be excluded. Follow-up data could exclude major side effects.
Conclusion: These data support the feasibility and preliminary safety of adenoviral transfection with HIF-1a in CAD. The ability of HIF-1a to initiate neo angiogenesis requires further study.