Kashaki Mandana, Mohazzab Arash, Radgoudarzi Mohammad, Bordbar Arash, Dabbagh Sama
Shahid Akbar Abadi Clinical Research Development Unit (ShACRDU), School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
Equally first author, School of Public Health, Iran University of Medical sciences, Tehran, Iran.
Pediatr Neonatol. 2025 Jan;66(1):44-49. doi: 10.1016/j.pedneo.2023.12.007. Epub 2024 May 22.
Persistent Pulmonary Hypertension of the newborn (PPHN) is characterized by sustained elevated Pulmonary Artery Pressure (PAP). Drug resistance and the adverse effects of current therapeutic agents warrant investigation of other targeted therapies. Bosentan has shown benefits in affected neonates. However, trials reported the association with unwanted effects. Thus, in this study, we assess another agent in the same family, Macitentan. However, its efficacy in the treatment of PPHN is not yet reported. Hence, this study evaluated the effect of Macitentan compared to Bosentan in terms of efficacy and safety in the treatment of PPHN.
This randomized, double-blinded non-inferiority clinical trial was conducted in Shahid Akbar Abadi hospital, Tehran, Iran. Sixty clinically stable neonates with signs suggestive of PPHN were randomly allocated into two groups (n = 30 in each group) and they received either Bosentan 1 mg/kg/dose BD (twice daily) or Macitentan 1 mg/kg/dose BD simultaneously with sildenafil. The echocardiographic and laboratory indices of efficacy and safety were compared between groups. SPAP (systolic pulmonary artery pressure) was used to assess the non-inferiority of the Macitentan compared to the Bosentan in their respective doses used in the study.
Participants' mean (SD) age was 3.53 (1.21) days, and 55% were female. No mortality case occurred. SPAP was reduced in both Bosentan and Macitenan groups with the mean difference in SPAP of 9 (95% CI: 7.34-10.65) in Bosentan and SPAP mean difference of 14 (95% CI: 12.12-15.86) in Macitentan group. Categorical comparison of primary outcome improvement showed that Macitentan was superior to Bosentan with a 10% non-inferiority margin. Similar results were obtained in other echocardiographic indices. Also, no significant alterations were observed in laboratory safety parameters.
Macitentan 1 mg/kg/dose BD (twice daily) is non-inferior to Bosentan 1 mg/kg/dose BD in improving echo outcomes of PPHN and it was even more effective in improving some of these. Also, it is non-inferior to Bosentan in terms of safety. TRIAL REGISTRY NUMBER: (IRCT20160120026115N9).
新生儿持续性肺动脉高压（PPHN）的特征是肺动脉压力（PAP）持续升高。当前治疗药物的耐药性及不良反应促使人们研究其他靶向治疗方法。波生坦已在受影响的新生儿中显示出益处。然而，试验报道了其存在不良影响。因此，在本研究中，我们评估了同一类药物中的另一种药物——马昔腾坦。然而，其治疗PPHN的疗效尚未见报道。因此，本研究比较了马昔腾坦与波生坦在治疗PPHN方面的疗效和安全性。
本随机、双盲、非劣效性临床试验在伊朗德黑兰的沙希德·阿克巴·阿巴迪医院进行。60例临床症状稳定且有PPHN迹象的新生儿被随机分为两组（每组n = 30），他们分别接受波生坦1 mg/kg/剂量，每日两次（BD）或马昔腾坦1 mg/kg/剂量，每日两次，并同时服用西地那非。比较两组间的超声心动图和实验室疗效及安全性指标。使用收缩期肺动脉压（SPAP）来评估马昔腾坦相对于波生坦在本研究中使用的各自剂量下的非劣效性。
参与者的平均（标准差）年龄为3.53（1.21）天，55%为女性。未发生死亡病例。波生坦组和马昔腾坦组的SPAP均降低，波生坦组SPAP的平均差值为9（95%置信区间：）7.34 - 10.65），马昔腾坦组SPAP的平均差值为14（95%置信区间：12.12 - 15.86）。主要结局改善的分类比较显示，马昔腾坦优于波生坦，非劣效性边际为10%。在其他超声心动图指标上也得到了类似结果。此外，实验室安全参数未观察到显著变化。
马昔腾坦1 mg/kg/剂量，每日两次（BD）在改善PPHN的超声心动图结局方面不劣于波生坦1 mg/kg/剂量，每日两次，并且在改善其中一些结局方面更有效。此外，在安全性方面不劣于波生坦。试验注册号：（IRCT20160120026115N9）
