Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05651347




Registration number
NCT05651347
Ethics application status
Date submitted
23/08/2022
Date registered
15/12/2022
Date last updated
15/12/2022

Titles & IDs
Public title
Antenatal Melatonin Supplementation for Neuroprotection in Fetal Growth Restriction
Scientific 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
Secondary ID [1] 0 0
U1111-1203-6718
Universal Trial Number (UTN)
Trial acronym
PROTECTMe
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fetal Growth Retardation 0 0
Stillbirth and Fetal Death 0 0
Pregnancy Preterm 0 0
Condition category
Condition code
Reproductive Health and Childbirth 0 0 0 0
Complications of newborn
Reproductive Health and Childbirth 0 0 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 0 0 0 0
Fetal medicine and complications of pregnancy
Reproductive Health and Childbirth 0 0 0 0
Abortion
Reproductive Health and Childbirth 0 0 0 0
Antenatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Placebo
Treatment: Drugs - Melatonin 10 MG

Placebo comparator: Placebo - Visually identical placebo tablets containing no active ingredient to the active treatment, administered three times a day.

Active comparator: Melatonin - 10mg Melatonin tablets, administered three times a day (a total daily dose of 30mg per day)


Other interventions: Placebo
Tablets, visually identical to the melatonin tablets, but containing no active ingredient are administered three times a day.

Treatment: Drugs: Melatonin 10 MG
Melatonin 10 mg tablets will be administered three times a day, up to a maximum of 30 mg daily
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Neurodevelopmental performance at 2 years of life among survivors of early onset FGR.
Timepoint [1] 0 0
24-36 months corrected age
Secondary outcome [1] 0 0
Incidence of patient reported side effects and adverse events with melatonin use in pregnancy
Timepoint [1] 0 0
From randomisation until cessation of trial medication at birth, assessed for up to 18 weeks.
Secondary outcome [2] 0 0
Incidence of patient reported daytime somnolence with melatonin use in pregnancy
Timepoint [2] 0 0
From randomisation until cessation of trial medication at birth, assessed for up to 18 weeks.
Secondary outcome [3] 0 0
Rate of altered maternal end-organ performance with melatonin supplementation
Timepoint [3] 0 0
Pre-intervention until 2 weeks post-commencement of intervention
Secondary outcome [4] 0 0
Impact of melatonin on fetal growth
Timepoint [4] 0 0
From randomisation until birth, for up to 17 weeks
Secondary outcome [5] 0 0
Impact of melatonin on fetoplacental Dopplers
Timepoint [5] 0 0
From randomisation until birth, assessed for up to 17 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/05/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/01/2026
Actual
Sample size
Target
336
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
The Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Royal Prince Alfred - Camperdown
Recruitment hospital [3] 0 0
John Hunter Hospital - Newcastle
Recruitment hospital [4] 0 0
Royal Hospital for Women - Randwick
Recruitment hospital [5] 0 0
Mater Misericordiae - South Brisbane
Recruitment hospital [6] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [7] 0 0
Women's and Children's Hospital - North Adelaide
Recruitment hospital [8] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [9] 0 0
Eastern Health - Box Hill
Recruitment hospital [10] 0 0
Monash Health - Clayton
Recruitment hospital [11] 0 0
Mercy Hospital - Heidelberg
Recruitment hospital [12] 0 0
Royal Women's Hospital - Parkville
Recruitment hospital [13] 0 0
Joan Kirner Hospital - Saint Albans
Recruitment hospital [14] 0 0
King Edward Memorial Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2305 - Newcastle
Recruitment postcode(s) [4] 0 0
2031 - Randwick
Recruitment postcode(s) [5] 0 0
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
4215 - Southport
Recruitment postcode(s) [7] 0 0
5006 - North Adelaide
Recruitment postcode(s) [8] 0 0
7000 - Hobart
Recruitment postcode(s) [9] 0 0
3128 - Box Hill
Recruitment postcode(s) [10] 0 0
3168 - Clayton
Recruitment postcode(s) [11] 0 0
3084 - Heidelberg
Recruitment postcode(s) [12] 0 0
3052 - Parkville
Recruitment postcode(s) [13] 0 0
3021 - Saint Albans
Recruitment postcode(s) [14] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch
Country [3] 0 0
New Zealand
State/province [3] 0 0
Palmerston North
Country [4] 0 0
New Zealand
State/province [4] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Other
Name
Monash University
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Cerebral Palsy Alliance
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Equity Trustees
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05651347
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Kirsten Palmer, PhD
Address 0 0
Monash University & Monash Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kirsten Palmer, PhD
Address 0 0
Country 0 0
Phone 0 0
+61 3 9594 5145
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05651347