Tadalafil for fetus with early-onset growth restriction (TADAFER IIb)

JRCT ID: jRCTs041190065

Registered date:02/09/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Fetal growth restriction
• Date of first enrollment: 01/10/2019
• Target sample size: 180
• Study type: Interventional
• Intervention(s): Oral administration of Tadalafil 20mg/day, 40mg/day or Placebo added to the conventional management. Tadalafil treatment is continued until delivery.

Outcome(s)

Primary Outcome

Prolongation of gestational age at birth (days)
Comparison of group A (placebo) and group B (tadalafil 20 mg/day) , and comparison of group A (placebo) and group C (tadalafil 40 mg/day)

Secondary Outcome

1.Completion rate of the treatment regimen
2.Prolongation of gestational age at birth
Comparison of group B (tadalafil 20 mg/day) and group C (tadalafil 40 mg/day)
3.Efficacy monitoring
3.1 Kaplan-Meier curve for duration of pregnancy
3.2 Estimated fetal weight
3.3 Fetal growth velocity
3.4 Fetal growth velocity in the 2 weeks after the protocol-defined treatment
3.5 Fetal growth rate in the 2 weeks after the protocol-defined treatment, and from the first day of the protocol-defined treatment to birth
3.6 Fetal head circumference
3.7 Fetal abdominal circumference
3.8 Doppler imaging of umbilical arterial blood flow, middle cerebral artery, uterine artery, and ductus venosus
3.9 Deepest amniotic fluid pocket or the deepest value of AFI
3.10 Birth weight of newborns
3.11 Standard deviation of birth weight of newborns
3.12 Birth height of newborns
3.13 Gender of newborns
3.14 Gestational age at birth
3.15 Rate of cesarean section or vaginal delivery
3.16 Maternal blood pressure and heart rate
3.17 Apgar score (1,5 min)
3.18 Umbilical artery pH and base excess values
3.19 Incidence rate of preeclampsia and days from the start of treatment to the onset
3.20 Analysis of maternal urine
3.21 Maternal serum PlGF, sFlt-1
3.22 Cause of delivery
3.23 Neonatal morbidity
3.24 Assessment of naonate at birth
4.Safety monitoring
4.1 Incidence rate of obstetric complications
4.2 Incidence rate of intrauterine demise
4.3 Perinatal mortality
4.4 Neonatal mortality
4.5 Maternal adverse event

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 45age old
• Gender: Female

Include criteria

1)Age 20 - 44
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 31 + 6 weeks.
4)The expected date of confinement is determined using the criteria of the guidelines for obstetrical practice in Japan (2017).
5)Singleton pregnancy
6)Written informed consent.

Exclude 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.

Related Information

• Primary Sponsor: Takakura Sho