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.
Trial registration number UMIN000023778.
- fetal growth restriction
- phosphodiesterase 5 inhibitor
- study protocol
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Contributors MiK TU wrote the manuscript. ST, YN, MK, CM and MN provided the biostatistical study design. SM, MaK, HT, MN, KT, KO, YK, ME, TaK, ToK, MN, AS and TI helped in the conception of the study.
Funding This work was supported by the Japan Agency for Medical Research and Development (AMED), JSPS KAKENHI Grant Number 17K16846, and in part by the Takeda Science Foundation.
Competing interests None declared.
Patient consent Not required.
Ethics approval This study was approved by the Institutional Review Board of Mie University Hospital on 25 August 2016 (no 3041) prior to patient enrolment. The study protocol was also approved by each institutional review board of all participating institutions. The study complies with the Helsinki Declaration.
Provenance and peer review Not commissioned; externally peer reviewed.
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