FUEL
Fontan Udenafil Exercise Longitudinal Trial
Patient / Population Intervention / Exposure Comparison Outcome
In 400 adolescents with Fontan circulation, udenafil did not significantly improve peak oxygen consumption compared with placebo, although exercise performance at the ventilatory anaerobic threshold improved.
N
400
Design
Phase-3, double-blind, placebo-controlled RCT over 26 weeks
Endpoint
Change in peak oxygen consumption at 26 weeks
Relevance
3
ResultPeak VO₂ +2.8 % vs −0.2 % (p=0.071) — primary endpoint missed. At the ventilatory anaerobic threshold, VO₂ (p=0.012), ventilatory efficiency (p=0.014) and work rate (p=0.021) all improved.
Goldberg DJ, Zak V, Goldstein BH, et al. Circulation. 2020;141(8):641-651. 10.1161/CIRCULATIONAHA.119.044352
Discussion & critique
The primary endpoint was formally missed and the submaximal gains are of uncertain clinical relevance, in a young and unusually well cohort. It is by far the largest randomised pharmacotherapy trial ever conducted in Fontan physiology and is why PDE5 inhibition remains an option rather than standard care.