UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Tadalafil treatment for Fetus with Early onset growth Restriction
Title of the study (Brief title)	Tadalafil treatment for Fetus with Early onset growth Restriction(TADAFER)
Region	Japan

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

Objectives
Narrative objectives1	To evaluate the safety of tadalafil study and estimate the maximum tolerated dose, to determine the recommended dose in Phase 2 trial
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase I

Assessment
Primary outcomes	Evaluation time: until after the end of the study four weeks from the start of study Safety of maternal and fetal (Maternal: biochemistry, urinalysis, electrocardiogram, concentration in the drug blood Fetus: chest abdominal X-ray, heart ultrasound examination, head ultrasound, blood drug concentration)
Key secondary outcomes	The maximum tolerated dose, the optimal dose, fetal abdominal circumference, estimated fetal weight, neonatal death, perinatal death, obstetric complications (gestational hypertension, preterm labor, placental abruption), birth weight, birth weeks, Apgar score, umbilical artery blood gas, fetal arterial blood flow test, fetal venous blood flow test, uterine artery blood flow test

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Dose comparison
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	3
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	The administration period: until delivery (after 34 weeks the judgment of the physician, up to 37 weeks) Dose and method: 3 cases cohort Cohort 1: tadalafil once a day, once 10 mg <Zalutia(5 mg) 2 tablets> daily administration
Interventions/Control_2	The administration period: until delivery (after 34 weeks the judgment of the physician, up to 37 weeks) Dose and method: 3 cases cohort Cohort 2: tadalafil once a day, once 20 mg <Adcirca(20 mg) 1 tablet> daily administration
Interventions/Control_3	The administration period: until delivery (after 34 weeks the judgment of the physician, up to 37 weeks) Dose and method: 3 cases cohort Cohort 3: tadalafil once a day, once 40 mg <Adcirca(20 mg) 2 tablets> daily administration
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) Fetal growth restriction (less than -1.5SD) 2) Healthy pregnancy 22 weeks after less than 34 weeks 3) Single pregnancy 4) 20 years of age or older 5) For the test participation, it has consent is obtained in writing from the patient.
Key exclusion criteria	1) Patients with allergic to tadalafil 2) Patients are taking the drug, which is contraindicated to tadalafil 3) Patients are undergoing kidney dialysis, with severe renal impairment(creatinine clearance<30mL / min) 4) Patients with severe liver failure [AST (GOT) or ALT (GPT)>100 IU / L] 5) Patients with uncontrolled arrhythmias, hypotension (blood pressure <90 / 50mmHg), or uncontrolled high blood pressure (blood pressure> 170 / 100mmHg) 6) Fetus with chromosomal abnormality can be considered from ultrasonography 7) Retinitis pigmentosa patients 8) Patients with bleeding disorders or peptic ulcer 9) Patients with pulmonary venous occlusive disease 10) Patient is determined to be unsuitable as a study subject
Target sample size	12

Research contact person
Name of lead principal investigator	Tomoaki Ikeda
Organization	Mie University Faculty of Medicine
Division name	Department of Obstetrics & Gynecology
Address	2-174 Edobashi Tsu-city Mie
TEL	059-232-1111
Email	t-ikeda@clin.medic.mie-u.ac.jp

Public contact
Name of contact person	Michiko Kubo
Organization	Mie University Faculty of Medicine
Division name	Department of Obstetrics & Gynecology
Address	2-174 Edobashi Tsu-city Mie
TEL	059-232-1111
Homepage URL
Email	mkubo@clin.medic.mie-u.ac.jp

Sponsor
Institute	Department of Obstetrics & Gynecology Mie University Faculty of Medicine
Institute
Department

Funding Source
Organization	Department of Obstetrics & Gynecology Mie University Faculty of Medicine
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization	Japan

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

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	三重大学医学部附属病院産科婦人科(三重県)

Other administrative information
Date of disclosure of the study information	2015 Year 12 Month 03 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2015 Year 11 Month 30 Day
Anticipated trial start date	2015 Year 12 Month 03 Day
Last follow-up date	2017 Year 10 Month 31 Day
Date of closure to data entry	2017 Year 10 Month 31 Day
Date trial data considered complete	2017 Year 10 Month 31 Day
Date analysis concluded	2017 Year 10 Month 31 Day

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2015 Year 12 Month 03 Day
Last modified on	2016 Year 09 Month 03 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000022459