Safety Evaluation of Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER): Results from the Phase II Trial
Safety Evaluation of Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER): Results from the Phase II Trial
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DOI：
10.3390/jcm8060856
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发表时间：
2019-06-01
影响因子：
3.9
通讯作者：
Ikeda, Tomoaki
中科院分区：
文献类型：
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作者：
Maki, Shintaro;Tanaka, Hiroaki;Ikeda, Tomoaki
他达拉非是一种磷酸二酯酶5（PDE 5）抑制剂，具有半衰期长、选择性高和起效快的特点。由于使用PDE 5抑制剂作为胎儿生长受限（FGR）治疗药物的安全性在全球范围内一直是一个问题，因此本文主要关注在他达拉非治疗早发性生长受限胎儿（TADAFER）II人群中进行的安全性评估。在停止试验后6个月，除了胎儿、新生儿和婴儿死亡病例外，还分析了新生儿和母体不良事件。在2016年9月至2018年3月期间研究了89例FGR孕妇（他达拉非和常规治疗组分别为45例和44例）。对照组有7例（16%）死亡（4例胎儿、1例新生儿和2例婴儿），而他达拉非组仅发生1例新生儿死亡。尽管他达拉非组中头痛、面部潮红和鼻出血的发生率更高，但这些症状均为1级且为一过性。总之，本试验表明他达拉非可降低FGR相关的胎儿和婴儿死亡率。这被认为主要是由于妊娠期延长。他达拉非治疗早发性FGR的疗效有待进一步研究。
Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor with a long half-life, high selectivity, and rapid onset of action. Because the safety of using PDE5 inhibitors as therapeutic agents for fetal growth restriction (FGR) has been a problem worldwide, this paper primarily focuses on the safety assessments performed in the Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER) II population. Neonatal and maternal adverse events were analyzed, in addition to fetal, neonatal, and infant death cases, six months after stopping the trial. Eighty-nine pregnant women with FGR were studied between September 2016 and March 2018 (45 and 44 in the tadalafil and conventional treatment groups, respectively). Seven (16%) deaths (four fetal, one neonatal, and two infant) in the control group, whereas only one neonatal death occurred in the tadalafil group. Although headache, facial flushing, and nasal hemorrhage occurred more frequently in the tadalafil group, these symptoms were Grade 1 and transient. In conclusion, this trial showed that tadalafil decreased the fetal and infant deaths associated with FGR. This is thought to be primarily due to pregnancy prolongation. Further studies are warranted to evaluate the efficacy of tadalafil in treating early-onset FGR.