Comparison of the effects of Bosentan and Sildenafil in treatment of Patent ductus arteriosus and pulmonary arterial hypertension in preterm infants : A randomized clinical trial.

Abstract

Abstract Background: Pulmonary arterial hypertension (PAH) is a common disorder in preterm neonates caused by patent ductus arteriosus (PDA). Although both sildenafil and bosentan have been shown to improve PAH, there is no study to compare the effect of these drugs in improving preterm infants with hemodynamically significant PDA and PAH. This study aimed to compare the therapeutic efficacy, safety, and possible side effects of combined therapies with Apotel + Bosentan, Apotel + Sildenafil, and Apotel alone in treating PDA and PAH in preterm infants. Methods: This clinical trial was conducted on 150 preterm neonates with PDA and PAH. Neonates were then divided into three groups and orally administrated with Apotel alone (10 mg/kg), Apotel (10 mg/kg) + Sildenafil (1 mg/kg), and Apotel (10 mg/kg) + Bosentan (1 mg/kg). Echocardiographic examination was performed before and 72h after the intervention. Results: Treatments with Apotel, Apotel + sildenafil, and Apotel + bosentan significantly decreased the mean of RV1, RV2, RV3, RVEDA, RVESA, RV/LV, TR intensity, TR PG, PI PG, and MPA diameter compared to before intervention (p<0.01). The mean of TAPSE after Apotel, Apotel + sildenafil, and Apotel + Bosentan administrations was significantly increased compared to before the study, indicating improvement in RV performance (p<0.01). The frequency of BPD and ROP in Apotel group (7.7% and 19.2%, respectively) was significantly lower than that in Apotel + sildenafil group (30% and 45%, respectively) and Apotel + bosentan (25% and 40%, respectively) groups (p<0.05). Conclusion: Oral administration of sildenafil and bosentan improved cardiac index beside its side effects in preterm infants PAH and PDA. Future clinical trial studies with larger sample sizes and long-term follow-up on term or near term neonates are recommended. Trial registration: IR.IUMS.FMD.REC.1399.430