Basic fibroblast growth factor in patients with intermittent claudication:Results of a phase I trial

OBJECTIVES This phase I study was designed to evaluate the safety, tolerabi lity and pharmacokinetics of intra-arterial basic fibroblast growth factor (bFGF) in patients with atherosclerotic peripheral arterial disease (PVD) a nd intermittent claudication. We also assessed the effects of basic fibrobl ast growth factor (bFGF) on calf blood flow as a measure of biologic activi ty. BACKGROUND Preclinical studies have shown that bFGF, an angiogenic peptide, promotes collateral development in animal models of myocardial and hind li mb ischemia. The safety and efficacy of bFGF in patients is unknown, and ea rly clinical trials are underway in coronary and peripheral arterial diseas e. METHODS A double-blind, placebo-controlled, dose-escalation trial was condu cted in patients with claudication demonstrating ankle/brachial index <0.8. Patients were randomly assigned to placebo (n = 6), 10 mu g/kg of bFGF (n = 4), 30 mu g/kg of bFGF once (n = 5) and 30 mu g/kg of bFGF on two consecu tive days (n = 4). Study drug was infused into the femoral artery of the is chemic leg. Detailed safety information including retinal photography for n eovascularization were obtained through one year. Calf blood flow was measu red with strain gauge plethysmography in the two higher dose treatment grou ps and in four placebo patients at baseline, one month and three to seven m onths after treatment. RESULTS Intra-arterial bFGF was safe and well-tolerated. The half-life was 46 +/- 21 min. Calf blood flow increased at one month by 66 +/- 26% (mean /- SEM) and at six months by 153 +/- 51% in bFGF-treated patients (n = 9, p = 0.002). Flow did not change significantly in the placebo group. CONCLUSIONS In this initial randomized, double-blind, placebo-controlled tr ial in patients with atherosclerotic PVD and claudication, bFGF was well-to lerated. The data suggest a salutary biologic effect, and initiation of pha se 2 trials is warranted. (J Am Coil Cardiol 2000;36:1239-44) (C) 2000 by t he American College of Cardiology.