Therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (the TRAFFIC study): a randomised trial.
BACKGROUND
Recombinant fibroblast growth factor-2 (rFGF-2) improves perfusion in models of myocardial and hindlimb ischaemia. We investigated whether one or two doses of intra-arterial rFGF-2 improves exercise capacity in patients with moderate-to-severe intermittent claudication.


METHODS
190 patients with intermittent claudication caused by infra-inguinal atherosclerosis were randomly assigned (1:1:1) bilateral intra-arterial infusions of placebo on days 1 and 30 (n=63); rFGF-2 (30 microg/kg) on day 1 and placebo on day 30 (single-dose, n=66); or rFGF-2 (30 microg/kg) on days 1 and 30 (double-dose, n=61). Primary outcome was 90-day change in peak walking time. Secondary outcomes included ankle-brachial pressure index and safety. The main analysis was per protocol.


RESULTS
Before 90 days, six patients had undergone peripheral revascularisation and were excluded, and ten withdrew or had missing data. 174 were therefore assessed for primary outcome. Peak walking time at 90 days was increased by 0.60 min with placebo, by 1.77 min with single-dose, and by 1.54 min with double-dose. By ANOVA, the difference between groups was p=0.075. In a secondary intention-to-treat analysis, in which all 190 patients were included, the difference was p=0.034. Pairwise comparison showed a significant difference between placebo and single-dose (p=0.026) but placebo and double-dose did not differ by much (p=0.45). Serious adverse events were similar in all groups.


CONCLUSIONS
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. The findings of TRAFFIC provide evidence of clinical therapeutic angiogenesis by intra-arterial infusion of an angiogenic protein.
Lederman
Robert J
RJ
Division of Cardiology, University of Michigan Health System, Ann Arbor, MI, USA. lederman@nih.gov
Mendelsohn
Farrell O
FO
Anderson
R David
RD
Saucedo
Jorge F
JF
Tenaglia
Alan N
AN
Hermiller
James B
JB
Hillegass
William B
WB
Rocha-Singh
Krishna
K
Moon
Thomas E
TE
Whitehouse
M J
MJ
Annex
Brian H
BH
D000368:Aged; D000704:Analysis of Variance; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007383:Intermittent Claudication / Q000188:drug therapy*; D007866:Leg / Q000098:blood supply; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016896:Treatment Outcome; D016138:Walking
D016222:Fibroblast Growth Factor 2