TY - JOUR
T1 - TADAFER II
T2 - Tadalafil treatment for fetal growth restriction - A study protocol for a multicenter randomised controlled phase II trial
AU - Umekawa, Takashi
AU - Maki, Shintaro
AU - Kubo, Michiko
AU - Tanaka, Hiroaki
AU - Nii, Masafumi
AU - Tanaka, Kayo
AU - Osato, Kazuhiro
AU - Kamimoto, Yuki
AU - Tamaru, Satoshi
AU - Ogura, Toru
AU - Nishimura, Yuki
AU - Kodera, Mayumi
AU - Minamide, Chisato
AU - Nishikawa, Masakatsu
AU - Endoh, Masayuki
AU - Kimura, Tadashi
AU - Kotani, Tomomi
AU - Nakamura, Masamitsu
AU - Sekizawa, Akihiko
AU - Ikeda, Tomoaki
N1 - Publisher Copyright:
© 2018 Author(s) (or their employer(s)).
PY - 2018
Y1 - 2018
N2 - Introduction There is no proven therapy to reverse or ameliorate fetal growth restriction (FGR). Sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, has been reported to potentially play a therapeutic role in FGR, but this has not been established. Tadalafil is also a selective PDE5 inhibitor. We have demonstrated the efficacy of tadalafil against FGR along with short-term outcomes and the feasibility of tadalafil treatment. Based on the hypothesis that tadalafil will safely increase the likelihood of increased fetal growth in FGR, we designed this phase II study to prospectively evaluate the efficacy and safety of tadalafil against FGR. Methods and analysis This study is a multicentre, randomised controlled phase II trial. A total of 140 fetuses with FGR will be enrolled from medical centres in Japan. Fetuses will be randomised to receive either the conventional management for FGR or a once-daily treatment with 20 mg of tadalafil along with the conventional management until delivery. The primary endpoint is fetal growth velocity from the first day of the protocol-defined treatment to birth (g/day). To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery was established in this study. The investigator will evaluate fetal baseline conditions at enrolment and will decide the timing of delivery based on this fetal indication. Infants will be followed up for development until 1.5 years of age. Ethics and dissemination This study was approved by the Institutional Review Board of Mie University Hospital and each participating institution. Our findings will be widely disseminated through peer-reviewed publications.
AB - Introduction There is no proven therapy to reverse or ameliorate fetal growth restriction (FGR). Sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, has been reported to potentially play a therapeutic role in FGR, but this has not been established. Tadalafil is also a selective PDE5 inhibitor. We have demonstrated the efficacy of tadalafil against FGR along with short-term outcomes and the feasibility of tadalafil treatment. Based on the hypothesis that tadalafil will safely increase the likelihood of increased fetal growth in FGR, we designed this phase II study to prospectively evaluate the efficacy and safety of tadalafil against FGR. Methods and analysis This study is a multicentre, randomised controlled phase II trial. A total of 140 fetuses with FGR will be enrolled from medical centres in Japan. Fetuses will be randomised to receive either the conventional management for FGR or a once-daily treatment with 20 mg of tadalafil along with the conventional management until delivery. The primary endpoint is fetal growth velocity from the first day of the protocol-defined treatment to birth (g/day). To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery was established in this study. The investigator will evaluate fetal baseline conditions at enrolment and will decide the timing of delivery based on this fetal indication. Infants will be followed up for development until 1.5 years of age. Ethics and dissemination This study was approved by the Institutional Review Board of Mie University Hospital and each participating institution. Our findings will be widely disseminated through peer-reviewed publications.
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U2 - 10.1136/bmjopen-2017-020948
DO - 10.1136/bmjopen-2017-020948
M3 - Article
C2 - 30381311
AN - SCOPUS:85055812066
SN - 2044-6055
VL - 8
JO - BMJ Open
JF - BMJ Open
IS - 10
M1 - e020948
ER -