Severe early - onset Intrauterine Growth Restriction (IUGR), (also referred to as Fetal growth restriction) diagnosed between 22+0 and 29+6 gestational age. IUGR is defined as an estimated fetal weight <10th centile OR Abdominal circumference <10th centile AND absent or reversed end diastolic flow in the umbilical artery. MedDRA version: 19.0 Level: LLT Classification code 10070532 Term: Fetal growth restriction System Organ Class: 100000004868
Conditions
Interventions
Trade Name: Sildenafil Activis
Product Name: Sildenafil Citrate
Pharmaceutical Form: Capsule, soft
Pharmaceutical form of the placebo: Capsule, soft
Route of administration of the placebo: Oral use
Sponsors
University College Cork
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All legally adult women with a diagnosis of a pregnancy affected by severe early-onset IUGR between 22+0 and 29+6 weeks of gestation will be considered for randomisation. Inclusion criteria: • Singleton pregnancy with severe, early-onset IUGR between 22+0 and 29+6 AND a clinical decision to manage expectantly • IUGR is defined as an estimated fetal weight =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Multiple pregnancy • Known or suspected structural or chromosomal fetal abnormality • Maternal illness (such as pre-eclampsia), which is expected to require delivery for maternal reasons within 72 hours • Maternal wish not to have active management of the pregnancy, such as a decision to have termination of pregnancy • Inability to give informed consent • Cocaine use • Contraindication to sildenafil therapy, e.g. known maternal cardiac disease, left ventricular outflow tract obstruction, concomitant treatment with nitrates or previous allergy to sildenafil.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The overarching aim is to determine whether maternal treatment with oral sildenafil citrate improves perinatal outcomes in pregnancies complicated by severe early-onset IUGR without increasing risks to the mother. This study has a specific objective to evaluate the clinical efficacy of sildenafil i.e. its ability to lead to a delay of a clinical indication for delivery on fetal grounds by at least one week. The other specific objective is to add to our understanding of the mechanism of action of sildenafil by monitoring changes in the maternal, utero-placental and fetal circulation. ;Secondary Objective: *Investigate impact on fetal growth & well-being by comparing differential effect on the vascular resistance in the uterine arteries, umbilical, fetal middle cerebral artery and fetal ductus venosus & differences in birth weight centiles in infants treated in-utero with sildenafil & placebo *Examine, in collaboration with an international consortium, the hypothesis that sildenafil increases rate of infant survival free of major handicap compared to placebo *Report frequency of adverse & serious adverse events associated with sildenafil use *Investigate the impact on maternal cardiovascular parameters by measuring maternal heart rate & peripheral blood pressure before & after administration of IMP *Elucidate the precise mechanism & location of action of sildenafil in pregnancy by investigating the effects of sildenafil on omental (representative of the wider maternal systemic vasculature), myometrial (uterine vasculature) & chorionic plate artery (placental vasculature) reactivity;Primary end point(s): The primary endpoint is: To determine whether sildenafil compared to placebo therapy delays the need to deliver a severely growth restricted fetus by a minimum of one week.;Timepoint(s) of evaluation of this end point: This endpoint will be evaluated from delivery/postnatal data. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Infant endpoints include: 1. gestational age at birth 2. survival to discharge 3. birth weight centile 4. length of admission on the Neonatal Intensive Care Unit 5. oxygen dependency at day 28 and 36 weeks corrected age 6. necrotising enterocolitis 7. retinopathy of prematurity 8. significant (grade III/IV) cerebral haemorrhage detected by cerebral ultrasound 9. number of doses of surfactant 10. ventilator days 11. supplemental oxygen days 12. number of days to full feeds Maternal endpoints include: 1. mode of delivery 2. standardised blood pressure and pulse monitoring during treatment 3. pre-eclampsia 4. postpartum haemorrhage 5. recording of the side effects e.g. headache, facial flushing 6. in-patient postnatal stay ;Timepoint(s) of evaluation of this end point: These endpoints will be evaluated from delivery/postnatal data and neonatal data. | — |
Countries
Ireland
Contacts
Public ContactAlice Power
University College Cork
Outcome results
None listed