A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension.
Level 2 - randomized trial
Individual randomized double-blind placebo-controlled trial
PubMed 22128226 · doi:10.1161/CIRCULATIONAHA.110.016667
What was done
A total of 235 treatment-naive children (weight ≥8 kg, aged 1–17 years) with pulmonary arterial hypertension were randomized to low-, medium-, or high-dose oral sildenafil or placebo three times daily for 16 weeks (STARTS-1). The primary comparison was percent change from baseline in peak oxygen consumption (PV(O2)) for all three sildenafil doses combined versus placebo, measured in 115 children capable of performing reliable exercise testing. Secondary endpoints evaluated in all participants included hemodynamics and functional class, with completers eligible for the ongoing STARTS-2 extension study.
What was found
The estimated mean ± SE percent change in PV(O2) for the three sildenafil doses combined versus placebo was 7.7 ± 4.0% (95% CI, -0.2% to 15.6%; P=0.056). Medium and high doses improved PV(O2), functional class, and hemodynamics compared with placebo, whereas low-dose sildenafil was ineffective (numerical values per subgroup not provided in abstract). Most adverse events were mild to moderate, but an increase in mortality was observed with higher doses in the STARTS-2 extension study.
Why it matters
This study provides evidence on dose-dependent efficacy of sildenafil in pediatric pulmonary arterial hypertension. It demonstrates clinical improvement with medium doses while revealing critical mortality risks associated with higher doses in children.
Limits
The primary composite endpoint narrowly missed statistical significance (P=0.056). Exercise testing for the primary outcome could only be completed by 115 of the 235 participants. The abstract lacks specific numeric data for hemodynamic measures, functional class improvements, and STARTS-2 mortality rates.