Topic: Reproductive health and childbirth
Conditions
Interventions
Participants are randomised to two arms:
Arm A: Sildenafil tablets 25 mg three times per day from baseline until delivery 31+6 weeks gestation, whichever comes first
Arm B: Placebo tablets 25 mg three
Sponsors
Liverpool Women's NHS Foundation Trust (UK)
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Women with singleton pregnancy and fetus diagnosed with severe, early onset intrauterine growth restriction (IUGR) between 22+0 and 29+6 weeks of gestation and clinical decision to manage pregnancy expectantly. 2. IUGR is defined as estimated fetal weight or abdominal circumference <10th centile and absent or reversed end diastolic velocity Doppler in the umbilical artery. 3. 16 years of age or older 4. Consent to take part in the trial
Exclusion criteria
Exclusion criteria: 1. Multiple pregnancy 2. Known or suspected structural or chromosomal fetal abnormality 3. Maternal illness (e.g., pre-eclampsia) that is expected to require delivery for maternal reasons within the next 72 hours 4. Maternal wish not to have active management of the pregnancy, or to have pregnancy termination weeks 5. Inability to give informed consent 6. Cocaine use 7. 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 |
|---|---|
| Difference in length of gestation (days): The primary outcome will be average prolongation of pregnancy for one week i.e. one week difference between two randomised groups in the mean randomisation to birth interval. Gestational age will be determined by early pregnancy dating ultrasound examination. The primary outcome was chosen as a surrogate for long-term morbidity as it has been shown that gestational age at birth remains the most powerful predictor of intact survival in early-onset IUGR cohorts. Recently published data from the 2006 English cohort of babies born between 22 and 26 weeks gestation showed a step increase in survivors without major morbidity ranging from 15% at 23 weeks to 50% at 26 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Fetal outcomes: 1. Abdominal circumference growth velocity defined as increase of abdominal circumference in mm per day 2. Changes in gestational age adjusted Doppler measurements expressed as pulsatility index in the umbilical artery, middle cerebral artery and ductus venosus and uterine arteries 3. Changes in short-term variability of the fetal heart rate recorded by transabdominal cardiotococography Infant outcomes include: 1. Gestational age at birth (days) 2. Survival to discharge 3. Birth weight centile 4. Length of admission on the Neonatal Intensive Care Unit (days) 5. Bronchopulmonary dysplasia requiring oxygen 36 weeks corrected age 6. Necostising enterocolotos (requiring surgery) 7. Retinopathy of prematurity (requiring treatment such as laser, grade 2/3 or more) 8. Severe central nervous system injury (detected by ultrasound and or MRI) periventricular leucomalacia grade II or more, intracerebral haemorrhage or more or hydrocephalus 9. Confirmed sepsis by positive blood culture 10. Patent ductus arteriosus needing medical or surgical treatment 11. Need for inotropes or vasopressors 12. Number of doses of surfactant 13. Ventilator days 14. Supplemental oxygen days 15. Number of days to full feeds Maternal safety monitoring including: 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 | — |
Countries
United Kingdom
Outcome results
None listed