Efficacy of milrinone plus sildenafil in the treatment of neonates with persistent pulmonary hypertension: A single center, randomized controlled trial from a resource limited setting.

Objective: To compare the outcomes of milrinone plus sildenafil versus sildenafil alone in the treatment of persistent pulmonary hypertension (PPH) in neonates. Study Design: Randomized Controlled Trial. Setting: Department of Neonatology, The Children’s Hospital and Institute of Child Health, Multan, Pakistan. Period: December 2023 to May 2024.  Methods: A total of 42 neonates, diagnosed to have PPH were enrolled. Neonates were randomized to either oral sildenafil monotherapy (n=21) or oral sildenafil and intravenous (IV) milrinone (n=21). Primary outcome was decrease in pulmonary artery systolic pressure (PASP). Secondary outcomes were improvement in oxygen saturation, duration of hospitalization, treatment related side effects, and mortality. Results: In a total of 42 neonates, 25 (59.5%) were boys. The mean age at the time of enrollment was 9.63±3.51 days. The mean PASP at the time of enrollment was 55.73±7.91 mmHg. PASP was statistically similar at baseline (p=0.5512), and day-3 (p=0.2163). At day-7, PASP was significantly reduced in sildenafil plus milrinone group was reported in comparison sildenafil group (37.62±8.04 mmHg vs. 42.92±8.25 mmHg, p=0.0413). SPO2, mortality, and post-treatment complications were statistically similar among neonates of both study groups. The duration of hospitalization was significantly less among neonates of sildenafil plus milrinone group vs. sildenafil group (13.58±2.93 days vs. 16.82±4.24 days, p=0.0063). Conclusion: Combined oral sildenafil and IV milrinone was more efficacious than sildenafil alone in reducing pulmonary arterial pressure.