Tadalafil treatment for fetuses with early-onset growth restriction: a protocol for a multicentre, randomised, placebo-controlled, double-blind phase II trial (TADAFER IIb)
Introduction TheTADAlafil treatment for Fetuses with early-onset growth Restriction: multicentrer, randomizsed, phase II trial (TADAFER II) study showed the possibility of prolonging the pregnancy period in cases of early-onset fetal growth restriction; however, it was an open-label study. To establ...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2022-06-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/12/6/e054925.full |
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| author | Hiroaki Tanaka Yasuhiro Tanaka Yoichi Aoki Masayuki Endo Tomoaki Ikeda Shintaro Maki Masafumi Nii Kayo Tanaka Satoshi Tamaru Toru Ogura Yuki Nishimura Tomomi Kotani Akihiko Sekizawa Masahiko Nakata Koji Nakamura Kenji Nagao Ichiro Yasuhi Hiroshi Kawamura Sho Takakura Mayumi Kotera Takafumi Ushida Norihiko Kikuchi Tadatsugu Kinjo Mayumi Takano Sachie Suga Michi Kasai Osamu Yasui Yuka Maegawa Shigeru Aoki Yoshio Yoshida |
| author_facet | Hiroaki Tanaka Yasuhiro Tanaka Yoichi Aoki Masayuki Endo Tomoaki Ikeda Shintaro Maki Masafumi Nii Kayo Tanaka Satoshi Tamaru Toru Ogura Yuki Nishimura Tomomi Kotani Akihiko Sekizawa Masahiko Nakata Koji Nakamura Kenji Nagao Ichiro Yasuhi Hiroshi Kawamura Sho Takakura Mayumi Kotera Takafumi Ushida Norihiko Kikuchi Tadatsugu Kinjo Mayumi Takano Sachie Suga Michi Kasai Osamu Yasui Yuka Maegawa Shigeru Aoki Yoshio Yoshida |
| author_sort | Hiroaki Tanaka |
| collection | DOAJ |
| description | Introduction TheTADAlafil treatment for Fetuses with early-onset growth Restriction: multicentrer, randomizsed, phase II trial (TADAFER II) study showed the possibility of prolonging the pregnancy period in cases of early-onset fetal growth restriction; however, it was an open-label study. To establish further evidence for the efficacy of tadalafil in this setting, we planned a multicentre, randomised, placebo-controlled, double-blind trial.Methods and analysis This trial will be conducted in 180 fetuses with fetal growth restriction enrolled from medical centres in Japan; their mothers will be randomised into three groups: arm A, receiving two times per day placebo; arm B, receiving one time per day 20 mg tadalafil and one time per day placebo and arm C, receiving 20 mg two times per day tadalafil. The primary endpoint is the prolongation of gestational age at birth, defined as days from the first day of the protocol-defined treatment to birth. To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery as in TADAFER II will be established in this trial. The investigator will evaluate fetal baseline conditions at enrolment and decide the timing of delivery based on this indication.Ethics and dissemination This study has been approved by Mie University Hospital Clinical Research Review Board on 22 July 2019 (S2018-007). Written informed consent will be obtained from all mothers before recruitment. Our findings will be widely disseminated through peer-reviewed publications.Trial registration jRCTs041190065. |
| first_indexed | 2024-04-13T20:03:44Z |
| format | Article |
| id | doaj.art-220d3336b2c54799bc15d81231003b99 |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2025-02-16T14:31:18Z |
| publishDate | 2022-06-01 |
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| series | BMJ Open |
| spelling | doaj.art-220d3336b2c54799bc15d81231003b992025-02-01T11:55:09ZengBMJ Publishing GroupBMJ Open2044-60552022-06-0112610.1136/bmjopen-2021-054925Tadalafil treatment for fetuses with early-onset growth restriction: a protocol for a multicentre, randomised, placebo-controlled, double-blind phase II trial (TADAFER IIb)Hiroaki Tanaka0Yasuhiro Tanaka1Yoichi Aoki2Masayuki Endo3Tomoaki Ikeda4Shintaro Maki5Masafumi Nii6Kayo Tanaka7Satoshi Tamaru8Toru Ogura9Yuki Nishimura10Tomomi Kotani11Akihiko Sekizawa12Masahiko Nakata13Koji Nakamura14Kenji Nagao15Ichiro Yasuhi16Hiroshi Kawamura17Sho Takakura18Mayumi Kotera19Takafumi Ushida20Norihiko Kikuchi21Tadatsugu Kinjo22Mayumi Takano23Sachie Suga24Michi Kasai25Osamu Yasui26Yuka Maegawa27Shigeru Aoki28Yoshio Yoshida291 Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu, Mie, Japan4 Department of Obstetrics and Gynecology, Shinshu University Graduate School of Medicine, Matsumoto, Nagano, Japan1Cancer Institute Hospital, Gynecologic Oncology, Koto-Ku, Japan8 Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan1 Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu, Mie, Japan1 Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu, Mie, Japan1 Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu, Mie, Japan1 Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu, Mie, Japan2 Clinical Research Support Center, Mie University Hospital, Tsu, Mie, Japan2 Clinical Research Support Center, Mie University Hospital, Tsu, Mie, JapanClinical Research Support Center, Mie University Hospital, Tsu, Mie, Japan3 Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan11 Department of Obstetrics and Gynecology, Showa University Graduate School of Medicine, Shinagawa-ku, Tokyo, Japan7 Department of Obstetrics and Gynecology, Toho University Faculty of Medicine, Otaku, Tokyo, Japan8 Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan12 Department of Obstetrics and Gynecology, Yokkaichi Municipal Hospital, Yokkaichi, Mie, Japan9 Department of Obstetrics and Gynecology, National Hospital Organization Nagasaki Medical Center, Omura, Nagasaki, Japan6 Department of Obstetrics and Gynecology, Fukui University Graduate School of Medicine, Fukui, Japan1 Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu, Mie, Japan2 Clinical Research Support Center, Mie University Hospital, Tsu, Mie, Japan3 Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan4 Department of Obstetrics and Gynecology, Shinshu University Graduate School of Medicine, Matsumoto, Nagano, Japan5 Department of Obstetrics and Gynecology, University of the Ryukyus, Nakagami-gun, Okinawa, Japan7 Department of Obstetrics and Gynecology, Toho University Faculty of Medicine, Otaku, Tokyo, Japan10 Department of Obstetrics and Gynecology, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan10 Perinatal Center for Maternity and Neonate, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan11 Department of Obstetrics and Gynecology, Showa University Graduate School of Medicine, Shinagawa-ku, Tokyo, Japan13 Department of Obstetrics and Gynecology, Mie Chuo Medical Center, Tsu, Mie, JapanPerinatal Center for Maternity and Neonate, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan6 Department of Obstetrics and Gynecology, Fukui University Graduate School of Medicine, Fukui, JapanIntroduction TheTADAlafil treatment for Fetuses with early-onset growth Restriction: multicentrer, randomizsed, phase II trial (TADAFER II) study showed the possibility of prolonging the pregnancy period in cases of early-onset fetal growth restriction; however, it was an open-label study. To establish further evidence for the efficacy of tadalafil in this setting, we planned a multicentre, randomised, placebo-controlled, double-blind trial.Methods and analysis This trial will be conducted in 180 fetuses with fetal growth restriction enrolled from medical centres in Japan; their mothers will be randomised into three groups: arm A, receiving two times per day placebo; arm B, receiving one time per day 20 mg tadalafil and one time per day placebo and arm C, receiving 20 mg two times per day tadalafil. The primary endpoint is the prolongation of gestational age at birth, defined as days from the first day of the protocol-defined treatment to birth. To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery as in TADAFER II will be established in this trial. The investigator will evaluate fetal baseline conditions at enrolment and decide the timing of delivery based on this indication.Ethics and dissemination This study has been approved by Mie University Hospital Clinical Research Review Board on 22 July 2019 (S2018-007). Written informed consent will be obtained from all mothers before recruitment. Our findings will be widely disseminated through peer-reviewed publications.Trial registration jRCTs041190065.https://bmjopen.bmj.com/content/12/6/e054925.full |
| spellingShingle | Hiroaki Tanaka Yasuhiro Tanaka Yoichi Aoki Masayuki Endo Tomoaki Ikeda Shintaro Maki Masafumi Nii Kayo Tanaka Satoshi Tamaru Toru Ogura Yuki Nishimura Tomomi Kotani Akihiko Sekizawa Masahiko Nakata Koji Nakamura Kenji Nagao Ichiro Yasuhi Hiroshi Kawamura Sho Takakura Mayumi Kotera Takafumi Ushida Norihiko Kikuchi Tadatsugu Kinjo Mayumi Takano Sachie Suga Michi Kasai Osamu Yasui Yuka Maegawa Shigeru Aoki Yoshio Yoshida Tadalafil treatment for fetuses with early-onset growth restriction: a protocol for a multicentre, randomised, placebo-controlled, double-blind phase II trial (TADAFER IIb) BMJ Open |
| title | Tadalafil treatment for fetuses with early-onset growth restriction: a protocol for a multicentre, randomised, placebo-controlled, double-blind phase II trial (TADAFER IIb) |
| title_full | Tadalafil treatment for fetuses with early-onset growth restriction: a protocol for a multicentre, randomised, placebo-controlled, double-blind phase II trial (TADAFER IIb) |
| title_fullStr | Tadalafil treatment for fetuses with early-onset growth restriction: a protocol for a multicentre, randomised, placebo-controlled, double-blind phase II trial (TADAFER IIb) |
| title_full_unstemmed | Tadalafil treatment for fetuses with early-onset growth restriction: a protocol for a multicentre, randomised, placebo-controlled, double-blind phase II trial (TADAFER IIb) |
| title_short | Tadalafil treatment for fetuses with early-onset growth restriction: a protocol for a multicentre, randomised, placebo-controlled, double-blind phase II trial (TADAFER IIb) |
| title_sort | tadalafil treatment for fetuses with early onset growth restriction a protocol for a multicentre randomised placebo controlled double blind phase ii trial tadafer iib |
| url | https://bmjopen.bmj.com/content/12/6/e054925.full |
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