Goldberg DJ, Zak V, Goldstein BH, et al. - Given that a total cavopulmonary connection created by the Fontan operation results in deterioration of cardiovascular efficiency associated with a decline in exercise performance, researchers conducted the FUEL Trial, a Phase III clinical trial, at 30 centers with the aim at improving physiology and guiding pharmacotherapy. They randomized participants to receive udenafil, 87.5 mg twice daily, or placebo in a 1:1 ratio. Between 2017 and 2019, 400 participants with Fontan physiology were randomized at 30 clinical sites in North America and the Republic of Korea. No improvement in oxygen consumption at peak exercise, but improvements in multiple measures of exercise performance at the ventilatory anaerobic threshold, was reported in correlation to treatment with udenafil (87.5 mg twice daily) in the FUEL trial.