Fetal Growth Retardation Clinical Trial
— PROTECTMeOfficial title:
A Triple-blinded, Randomized, Parallel-group Placebo-controlled Trial to Assess the Impact of Maternal Antenatal Melatonin Supplementation on Early Childhood Neurodevelopmental Outcomes in the Setting of Severe Preterm Fetal Growth Restriction
Fetal growth restriction (FGR) is a significant health care issue, affecting 20,000 Australian pregnancies every year. Undetected FGR is one of the key risk factors for stillbirth, but FGR can also cause significant impairments in short and long-term health outcomes for the child. It is a major risk factor for preterm birth and is a recognised causal pathway to the neurodevelopmental injury underlying cognitive and behavioural impairment and cerebral palsy. Current obstetric care is focused on the detection of the growth restricted fetus and then ultrasound assessment of fetal wellbeing to guide timing of delivery. This approach seeks to maximize the gestational age of the fetus at delivery to minimise the risks of prematurity, while delivering the fetus in time to reduce the likelihood of stillbirth. Currently, no therapies exist that can maximize fetal wellbeing in the setting of growth restriction and minimise the frequency of antenatally acquired brain injury due to in-utero hypoxia. This triple-blind, randomized, parallel group, placebo-controlled trial will administer maternal melatonin or placebo supplementation antenatally in the setting of early-onset severe FGR to determine whether melatonin can PROTECT the fetal brain and lead to improved neurodevelopmental outcomes.
Status | Recruiting |
Enrollment | 336 |
Est. completion date | January 31, 2026 |
Est. primary completion date | December 30, 2025 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Female |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Singleton Pregnancy 2. Severe fetal growth restriction, defined as: - Abdominal circumference =3rd centile for gestational age according to charts supplied that have been adapted from Westerway et al; or - Abdominal circumference <10th centile in combination with at least one abnormal fetoplacental Doppler study, being: - Uterine artery (raised pulsatility index =95th centile) - Umbilical artery (pulsatility index =95th centile or absent/reversed end-diastolic flow) 3. Confirmed 23+0 - 31+6 weeks' gestation 4. Age =18 years 5. Understand English Exclusion Criteria: 1. A fetus with a known chromosomal, major structural anomaly or non-placental cause of fetal growth restriction 2. Pregnancies requiring immediate delivery (e.g. absent A wave in ductus venosus, preterminal CTG or biophysical profile) 3. Co-recruitment in another clinical trial where a pharmaceutical product or nutritional supplement impacting on oxidative stress is the trial intervention. 4. Currently prescribed Fluvoxamine |
Country | Name | City | State |
---|---|---|---|
Australia | Eastern Health | Box Hill | Victoria |
Australia | Royal Prince Alfred | Camperdown | New South Wales |
Australia | Monash Health | Clayton | Victoria |
Australia | The Canberra Hospital | Garran | Australian Capital Territory |
Australia | Mercy Hospital | Heidelberg | Victoria |
Australia | Royal Hobart Hospital | Hobart | Tasmania |
Australia | John Hunter Hospital | Newcastle | New South Wales |
Australia | Women's and Children's Hospital | North Adelaide | South Australia |
Australia | Royal Women's Hospital | Parkville | Victoria |
Australia | Royal Hospital for Women | Randwick | New South Wales |
Australia | Joan Kirner Hospital | Saint Albans | Victoria |
Australia | Mater Misericordiae | South Brisbane | Queensland |
Australia | Gold Coast University Hospital | Southport | Queensland |
Australia | King Edward Memorial Hospital | Subiaco | Western Australia |
New Zealand | Auckland Hospital | Auckland | |
New Zealand | Middlemore Hospital | Auckland | |
New Zealand | Christchurch Hospital | Christchurch | |
New Zealand | Palmerston Hospital | Palmerston North | |
New Zealand | Wellington Regional Hospital | Wellington |
Lead Sponsor | Collaborator |
---|---|
Monash University | Cerebral Palsy Alliance, Equity Trustees, National Health and Medical Research Council, Australia |
Australia, New Zealand,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Neurodevelopmental performance at 2 years of life among survivors of early onset FGR. | The primary outcome will be identified by a change in the Bayley-IV Cognitive score of 5 or more points. | 24-36 months corrected age | |
Secondary | Incidence of patient reported side effects and adverse events with melatonin use in pregnancy | Maternal side effect profiles experienced, such as symptoms of abdominal cramps, flushing, migraines, gastrointestinal disturbance. This will be collected from the patient medication diary completed during treatment with reported side effects expressed as incidence (% patients). | From randomisation until cessation of trial medication at birth, assessed for up to 18 weeks. | |
Secondary | Incidence of patient reported daytime somnolence with melatonin use in pregnancy | Maternal symptoms of drowsiness, obtained from the patient completed medication diary, will be expressed as an average somnolence score (scale 1-10). | From randomisation until cessation of trial medication at birth, assessed for up to 18 weeks. | |
Secondary | Rate of altered maternal end-organ performance with melatonin supplementation | Haematological and biochemical investigations undertaken pre- and post- commencement of trial medication will be used to assess the rate of change in maternal end-organ function, particularly renal and liver function. | Pre-intervention until 2 weeks post-commencement of intervention | |
Secondary | Impact of melatonin on fetal growth | The antenatal use of melatonin on estimated fetal growth (grams) will be assessed using ultrasound biometry parameters performed fortnightly following trial recruitment until birth. The fetal growth trajectory across gestation will be compared to the placebo group. | From randomisation until birth, for up to 17 weeks | |
Secondary | Impact of melatonin on fetoplacental Dopplers | The antenatal use of melatonin on fetoplacental Dopplers performed fortnightly following trial recruitment until birth. The incidence of abnormal fetoplacental Doppler indices will be reported according to gestational age | From randomisation until birth, assessed for up to 17 weeks |
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