No registrations found.
ID
Source
Brief title
Health condition
Fetal growth restriction
Sponsors and support
Intervention
Outcome measures
Primary outcome
Intact neonatal survival until term age
Secondary outcome
1) To evaluate whether Sildenafil citrate, compared to placebo, increases the likelihood of improved fetal growth velocity assessed by ultrasound abdominal circumference measurements (AC);
2) To evaluate whether Sildenafil citrate, compared to placebo, increases the likelihood of age-adequate performance on the two-year Bayley scales of infant development (BSID)-III (composite cognitive score and composite motor score);
3) To assess co-incidence and severity of the maternal syndrome of pre-eclampsia / HELLP-syndrome
Background summary
Rationale: Severe, early-onset fetal growth restriction (FGR) due to placental insufficiency is associated with a high risk of perinatal morbidity with long-lasting sequelae and mortality. Placental insufficiency is the result of abnormal formation and function of the placenta (placentation) with inadequate remodelling of the maternal spiral (uteroplacental) arteries. There is currently no therapy available with demonstrated effectiveness. Evidence suggests Sildenafil citrate improves uteroplacental blood flow, growth, and meaningful outcomes.
Objective: To evaluate the effectiveness of sildenafil (versus placebo) in achieving healthy perinatal survival.
Study design: Multicenter nationwide randomized placebo-controlled clinical trial.
Study population: Women with a singleton pregnancy between 20 and 30 weeks with severe fetal growth restriction of likely placental origin, and with estimated significant likelihood of perinatal death.
Intervention: Sildenafil 25mg or placebo tablet orally three times daily.
Main study parameters/endpoints: Perinatal healthy survival, i.e. survival without severe neonatal morbidity at term age.
Study objective
Sildenafil citrate increases the likelihood of intact neonatal survival until term age for fetuses of pregnancies complicated by severe early-onset fetal growth restriction.
Study design
Term age, at discharge, at two years age (Bayley scales of infant development (BSID)-III)
Intervention
Sildenafil 25 mg or look-alike placebo tablets three times daily orally from randomization until delivery
Academisch Medisch Centrum (AMC)
Meibergdreef 9
Amsterdam 1105 AZ
The Netherlands
020 566 9111
j.w.ganzevoort@amc.uva.nl
Academisch Medisch Centrum (AMC)
Meibergdreef 9
Amsterdam 1105 AZ
The Netherlands
020 566 9111
j.w.ganzevoort@amc.uva.nl
Inclusion criteria
Inclusion criteria ((I OR II) AND III):
I. At 20+0-27+6 weeks: an ultrasound measurement of the fetal abdominal circumference (AC) <3rd percentile for gestational age or an ultrasound estimate of fetal weight (EFW) <5th percentile
OR
II. At 28+0-29+6 weeks: an ultrasound estimate of fetal weight (EFW) <700 grams using Hadlock C formula
AND
III. Likely placental origin defined by (a AND/OR b AND/OR c AND/OR d)
a. The presence of uterine artery notching
b. Abnormal flow velocity patterns of the umbilical artery or middle cerebral artery
c. Maternal hypertensive disorders
d. Low PlGF in point-of-care assessment
Exclusion criteria
I. Plan to terminate pregnancy for maternal or fetal indication within days
II. Known multiple pregnancy
III. Identified congenital anomalies or congenital infection
IV. Maternal age at eligibility <18 years
V. Cocaine use
VI. Current use of sildenafil
VII. Current use of cyp3A5 inhibitors: amiodaron, azitromycine, ciclosporine, claritromycine, diltiazem, erytromycine, fluconazol, itraconazol, ketoconazol, verapamil, voriconazol.
VIII. Recent myocardial infarction or stroke
Design
Recruitment
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL4592 |
| NTR-old | NTR4751 |
| CCMO | NL41894.018.12 |
| OMON | NL-OMON47435 |