UMIN-CTR Clinical Trial

Basic information
Public title	A multicenter phase II trial of the efficacy and safety of tadalafil in fetus with early-onset growth restriction.
Acronym	Tadalafil for fetus with early-onset growth restriction (TADAFER 2)
Scientific Title	A multicenter phase II trial of the efficacy and safety of tadalafil in fetus with early-onset growth restriction.
Scientific Title:Acronym	Tadalafil for fetus with early-onset growth restriction (TADAFER 2)
Region	Japan

Condition
Condition	Fetal growth restriction
Classification by specialty	Obsterics and gynecology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	The purpose of this randomized phase II trial is to assess the efficacy and safety of tadalafil in fetus with growth restriction.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Phase II

Assessment
Primary outcomes	Fetal growth velocity (g/day) from enrollment to birth.
Key secondary outcomes	1. Completion rate of the treatment regimen. 2. Efficacy monitoring. 2.1 Estimated fetal weight (g). 2.2 Fetal growth velocity (g/day) during two weeks from enrollment and one week after enrollment (g/day). 2.3 Fetal growth rate. 2.4 Fetal head circumference (cm). 2.5 Doppler imaging of umbilical arterial blood flow. 2.6 Deepest amniotic fluid pocket (cm). 2.7 Prolongation of gestational age at birth (days). 2.8 Birth weight (g). 2.9 Gestational age at birth. 2.10 Apgar score. 2.11 Umbilical artery pH and base excess values. 2.12 Incidence rate of preeclampsia. 2.13 Neonatal morbidity. 2.14 Offspring outcome until 1.5 years of age. 3. Safety monitoring. 3.1 Incidence rate of obstetric complications. 3.2 Perinatal mortality. 3.3 Neonatal mortality.

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	NO
Dynamic allocation	YES
Institution consideration	Institution is considered as adjustment factor in dynamic allocation.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Arm A: The conventional management of FGR consisted of evaluation of fetal well-being by ultrasonography including Doppler imaging and fetal heart rate monitoring to evaluate possible pregnancy termination.
Interventions/Control_2	Arm B: Oral administration of Tadalafil (20mg/day) added to the conventional management. Tadalafil treatment is continued until delivery.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Female
Key inclusion criteria	1) Age>=20 2) Estimated fetal weight (EFW) less than 1.5 standard deviations of the mean EFW for gestational age. 3) Gestational age between 20 + 0 and 33 + 6 weeks. 4) The expected date of confinement is determined using the criteria of the guidelines for obstetrical practice in Japan (2014). 5) Singleton pregnancy 6) Written informed consent.
Key exclusion criteria	1) A result from antepartum fetal tests consisted of ultrasonography including Doppler imaging and fetal heart rate monitoring at eligibility indicates that delivery should be attempted. 2) A history of allergy to tadalafil 3) Concurrent medications that interact adversely with tadalafil 4) Relative contraindication of tadalafil treatment due to renal disease. 5) Relative contraindication of tadalafil treatment due to liver disease. 6) Relative contraindication of tadalafil treatment due to uncontrolled arrhythmia, hypertension (BP >170/110 mmHg), and hypotension (BP <80/40 mmHg). 7) Fetus with suspected chromosomal disorder and/or multiple congenital anomalies. 8) Relative contraindication of tadalafil treatment due to retinitis pigmentosa, coagulation defect, active gastric and/or intestinal ulcer, and venous obstructive disease. 9) Attending physician decides to entry inappropriate.
Target sample size	140

Research contact person
Last name of lead principal investigator	1st name Middle name Last name Tomoaki Ikeda
Organization	Mie university hospital
Division name	Department of Obstetrics and Gynecology
Zip code
Address	2-174 Edobashi, Tsu-city
TEL	059-232-1111
Email	tadafer.study@gmail.com

Public contact
1st name of contact person	1st name Middle name Last name Shintaro Maki, Michiko Kubo, Takashi Umekawa
Organization	Mie university hospital
Division name	Department of Obstetrics and Gynecology
Zip code
Address	2-174 Edobashi, Tsu-city
TEL	059-232-1111
Homepage URL
Email	tadafer.study@gmail.com

Sponsor
Institute	Mie university hospital, Department of Obstetrics and Gynecology
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development (AMED)
Organization
Division
Category of Funding Organization	Government offices of other countries
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	三重大学病院(三重県)

Other administrative information
Date of disclosure of the study information	2016 Year 08 Month 26 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2016 Year 08 Month 25 Day
Date of IRB	2016 Year 08 Month 25 Day
Anticipated trial start date	2016 Year 09 Month 01 Day
Last follow-up date	2018 Year 04 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2016 Year 08 Month 26 Day
Last modified on	2019 Year 03 Month 27 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000027132