Fibroblast Growth Factor Improves Severe Claudication

Laurie Barclay, MD

June 13, 2002

June 14, 2002 -- Recombinant fibroblast growth factor-2 (rFGF-2) may enhance angiogenesis and improve severe claudication in patients at high risk for amputation or in whom bypass is not feasible, according to results of the TRAFFIC study reported in the June 15 issue of The Lancet.

"Angiogenesis is an extremely exciting area with a great deal of potential. This study provides the strongest and most convincing data to date that an angiogenic agent can have a positive effect in humans," senior author Brian Annex, MD, from Duke University Medical Center in Durham, N.C., said in a news release. "It is also one that has been in need of positive randomized, placebo-controlled data to accelerate further research. This study is an important step in that direction, [because it is] the first to show a positive result in its primary endpoint."

The Therapeutic Angiogenesis with FGF for Intermittent Claudication (TRAFFIC) study was a multicenter, phase II, double-blinded, controlled trial enrolling 190 patients with intermittent claudication of the calf muscle caused by atherosclerosis.

Subjects were randomly assigned to a control group receiving bilateral intra-arterial infusions of placebo on days 1 and 30; a single-dose group receiving rFGF-2 (30 mcg/kg) on day 1 and placebo on day 30; or a double-dose group receiving rFGF-2 (30 mcg/kg) on days 1 and 30. Severe proteinuria appeared to be dose-related, occurring in 2% of patients in the placebo group, 5% in the single-dose group, and 8% in the double-dose group.

At 90 days, peak walking time increased by 14% (0.6 minutes) in the placebo group, by 34% (1.77 minutes) in the single-dose group, and by 20% (1.54 minutes) in the double-dose group ( P=.026 for single-dose compared with placebo). Improved scores in the ankle-brachial pressure index also suggest that rFGF-2 improved limb perfusion, although whether the mechanism involves angiogenesis, collateralization, or recanalization is not entirely clear.

"Intra-arterial rFGF-2 resulted in a significant increase in peak walking time at 90 days; repeat infusion at 30 days was no better than one infusion," said lead author Robert Lederman, MD, of the division of cardiology at the University of Michigan Health System in Ann Arbor. "The findings of TRAFFIC provide evidence of clinical therapeutic angiogenesis by intra-arterial infusion of an angiogenic protein."

However, the authors note study limitations and caution that the findings may not apply to patients with hemodynamically significant iliac stenosis.

In an accompanying commentary, Richard Donnelly, professor of medicine at the University of Nottingham, England, notes that "therapeutic angiogenesis in the lower limb would be especially attractive when revascularization is not feasible or has failed, or when the risks of critical ischemia and distal amputation are high."

Lancet. 2002;359:2053-2058

Reviewed by Gary D. Vogin, MD

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