Effect of Sildenafil on Mortality in Term Neonates with Hypoxemic Respiratory Failure due to Persistent Pulmonary Hypertension (SIPHON) - A Randomised Control Trial

Abstract

Introduction: Persistent Pulmonary Hypertension (PPHN) complicates the transition from intrauterine to extrauterine life in some neonates. Sildenafil is known to reduce pulmonary pressures. However, its effect on reducing mortality is unclear. This study is conducted to determine the effect of Sildenafil in reducing all-cause mortality rate in term newborns with hypoxemic respiratory failure due to pulmonary hypertension.

Methods: This was a double-blinded randomised control trial done in a level 3 neonatal intensive care unit. Term neonates on mechanical ventilation with an Oxygenation Index (OI) > 15, and echocardiography suggesting PPHN were included in the study. The drug group received intravenous Sildenafil and the placebo group normal saline. The difference in the mortality rate between the two groups was analysed.

Results: Eleven babies were randomised to the drug group and 12 to the placebo group. Both the groups matched in terms of their baseline characteristics. The difference in the drop of OI and right ventricular systolic pressure (RVSP) between the drug and placebo groups was not statistically significant. The relative risk of mortality was 0.436 in the intervention group (95% CI 0.105 to 1.80). The difference in the mortality rate was not statistically significant with P- value of 0.252. The rate of complications such as necrotising enterocolitis, sepsis, and pneumothorax was not different between the two groups.

Conclusions: Intravenous sildenafil does not have any significant benefit over placebo in reducing all-cause mortality, oxygenation index, RVSP or complications when compared to placebo.