Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: Results of a phase I open-label dose escalation study

OBJECTIVES Evaluate the safety, tolerability and preliminary efficacy of in tracoronary (IC) basic fibroblast growth factor (bFGF, FGF-2). BACKGROUND FGF-2 is a heparin-binding growth factor capable of inducing fun ctionally significant angiogenesis in animal models of myocardial ischemia. METHODS Phase I, open-label dose-escalation study of FGF-2 administered as a single 20-min infusion in patients with ischemic heart disease not amenab le to treatment with CABG or PTCA. RESULTS Fifty-two patients enrolled in this study received IC FGF-2 (0.33 t o 48 mug/kg). Hypotension was dose-dependent and dose-limiting, with 36 mug /kg being the maximally tolerated dose. Four patients died and four patient s had non-Q-wave myocardial infarctions. Laboratory parameters and retinal examinations showed mild and mainly transient changes during the 6-month fo llow-up. There was an improvement in quality of life as assessed by Seattle Angina Questionnaire and improvement in exercise tolerance as assessed by treadmill exercise testing (510 +/- 24 s at baseline, 561 +/- 26 s at day 2 9 [p = 0.023], 609 +/- 26 s at day 57 (p < 0.001), and 633 +/- 24 s at day 180 (p < 0.001), overall p < 0.001). Magnetic resonance (MR) imaging showed increased regional wall thickening (baseline: 34 +/- 1.7%, day 29: 38.7 +/ - 1.9% [p = 0.006], day 57: 41.4 +/- 1.9% [p < 0.001], and day 180: 42.0 +/ - 2.3% [p < 0.001], overall p = 0.001) and a reduction in the extent of the ischemic area at all time points compared with baseline. CONCLUSIONS Intracoronary administration of rFGF-2 appears safe and is well tolerated over a 100-fold dose range (0.33 to 0.36 <mu>k/kg). Preliminary evidence of efficacy is tempered by the open-label uncontrolled design of t he study. (C) 2000 by the American College of Cardiology.