Safety Evaluation of Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER): Results from the Phase II Trial
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 assess...
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doaj-986dc5e2f8b24488a43f44cd70f923292020-11-24T21:40:39ZengMDPI AGJournal of Clinical Medicine2077-03832019-06-018685610.3390/jcm8060856jcm8060856Safety Evaluation of Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER): Results from the Phase II TrialShintaro Maki0Hiroaki Tanaka1Makoto Tsuji2Fumi Furuhashi3Shoichi Magawa4Michiko K. Kaneda5Masafumi Nii6Kayo Tanaka7Eiji Kondo8Satoshi Tamaru9Toru Ogura10Yuki Nishimura11Masayuki Endoh12Tadashi Kimura13Tomomi Kotani14Akihiko Sekizawa15Tomoaki Ikeda16Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, JapanDepartment of Obstetrics and Gynecology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, JapanDepartment of Obstetrics and Gynecology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, JapanDepartment of Obstetrics and Gynecology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, JapanDepartment of Obstetrics and Gynecology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, JapanDepartment of Obstetrics and Gynecology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, JapanDepartment of Obstetrics and Gynecology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, JapanDepartment of Obstetrics and Gynecology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, JapanDepartment of Obstetrics and Gynecology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, JapanClinical Research Support Center, Mie University Hospital, 2-174 Edobashi, Tsu, Mie 514-8507, JapanClinical Research Support Center, Mie University Hospital, 2-174 Edobashi, Tsu, Mie 514-8507, JapanClinical Research Support Center, Mie University Hospital, 2-174 Edobashi, Tsu, Mie 514-8507, JapanDepartment of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, JapanDepartment of Obstetrics and Gynecology, Showa University Graduate School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, JapanDepartment of Obstetrics and Gynecology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, JapanTadalafil 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.https://www.mdpi.com/2077-0383/8/6/856fetal growth restrictiontadalafilphosphodiesterase 5 inhibitor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shintaro Maki Hiroaki Tanaka Makoto Tsuji Fumi Furuhashi Shoichi Magawa Michiko K. Kaneda Masafumi Nii Kayo Tanaka Eiji Kondo Satoshi Tamaru Toru Ogura Yuki Nishimura Masayuki Endoh Tadashi Kimura Tomomi Kotani Akihiko Sekizawa Tomoaki Ikeda |
spellingShingle |
Shintaro Maki Hiroaki Tanaka Makoto Tsuji Fumi Furuhashi Shoichi Magawa Michiko K. Kaneda Masafumi Nii Kayo Tanaka Eiji Kondo Satoshi Tamaru Toru Ogura Yuki Nishimura Masayuki Endoh Tadashi Kimura Tomomi Kotani Akihiko Sekizawa Tomoaki Ikeda Safety Evaluation of Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER): Results from the Phase II Trial Journal of Clinical Medicine fetal growth restriction tadalafil phosphodiesterase 5 inhibitor |
author_facet |
Shintaro Maki Hiroaki Tanaka Makoto Tsuji Fumi Furuhashi Shoichi Magawa Michiko K. Kaneda Masafumi Nii Kayo Tanaka Eiji Kondo Satoshi Tamaru Toru Ogura Yuki Nishimura Masayuki Endoh Tadashi Kimura Tomomi Kotani Akihiko Sekizawa Tomoaki Ikeda |
author_sort |
Shintaro Maki |
title |
Safety Evaluation of Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER): Results from the Phase II Trial |
title_short |
Safety Evaluation of Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER): Results from the Phase II Trial |
title_full |
Safety Evaluation of Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER): Results from the Phase II Trial |
title_fullStr |
Safety Evaluation of Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER): Results from the Phase II Trial |
title_full_unstemmed |
Safety Evaluation of Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER): Results from the Phase II Trial |
title_sort |
safety evaluation of tadalafil treatment for fetuses with early-onset growth restriction (tadafer): results from the phase ii trial |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2019-06-01 |
description |
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. |
topic |
fetal growth restriction tadalafil phosphodiesterase 5 inhibitor |
url |
https://www.mdpi.com/2077-0383/8/6/856 |
work_keys_str_mv |
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