Trial registered on ANZCTR


Trial ID
ACTRN12611000491965
Ethics application status
Approved
Date submitted
28/04/2011
Date registered
11/05/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
MAGENTA - Magnesium Sulphate at 30 to 34 weeks' gestational age: Neuroprotection Trial
Scientific title
Does antenatal magnesium sulphate given to women at risk of imminent preterm birth (defined as planned or definitely expected in the next 24 hours) between 30 and 34 weeks' gestation reduce the risk of death or cerebral palsy in their children at 2 years corrected age? - a randomised controlled trial
Secondary ID [1] 259661 0
Nil
Universal Trial Number (UTN)
Trial acronym
MAGENTA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Complications of preterm infant 261230 0
Neuroprotection 265764 0
Cerebral Palsy 265765 0
Child health 265766 0
Condition category
Condition code
Reproductive Health and Childbirth 259375 259375 0 0
Antenatal care
Reproductive Health and Childbirth 265915 265915 0 0
Complications of newborn
Neurological 265916 265916 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Magnesium Sulphate (8% solution)- 50 ml infusion equivalent to 4g magnesium sulphate heptahydrate (16 mmol magnesium ions) administered through a dedicated intravenous line over 30 minutes. This is administered to women at risk of preterm birth between 30 and 34 weeks' gestation when birth is imminent (defined as planned or definitely expected in the next 24 hours).
Intervention code [1] 258089 0
Treatment: drugs
Intervention code [2] 264509 0
Prevention
Comparator / control treatment
Isotonic sodium chloride (0.9% solution) - 50 ml infusion administered through a dedicated intravenous line over 30 minutes. This is administered to women at risk of preterm birth between 30 and 34 weeks' gestation when birth is imminent (defined as planned or definitely expected in the next 24 hours).
Control group
Placebo

Outcomes
Primary outcome [1] 262192 0
The incidence of death or cerebral palsy defined as stillbirth, death of live born infant before hospital discharge, or death after hospital discharge before 2 years' corrected age; or any cerebral palsy [abnormality of tone with motor dysfunction].
Timepoint [1] 262192 0
2 years' corrected age.
Secondary outcome [1] 273296 0
For the infant:
Health outcomes considered to be important measures of mortality and morbidity prior to primary hospital discharge; (defined as stillbirth and death of liveborn infant before hospital discharge; intraventricular haemorrhage (IVH), severe IVH, cystic periventricular leukomalacia (PVL), neonatal encephalopathy, neonatal convulsions, proven necrotising enterocolitis, retinopathy of prematurity needing treatment, patent ductus arteriosus needing treatment, respiratory distress syndrome, severity of any neonatal lung disease, chronic lung disease (oxygen dependent at 36 weeks post-menstrual age), use of respiratory support, airleak requiring drainage, confirmed infection within the first 48 hours, infection after the first 48 hours, body size at birth (weight, length, head circumference) and at discharge home.
Timepoint [1] 273296 0
Up to hospital discharge.
Secondary outcome [2] 273297 0
Composite serious health outcome (defined as stillbirth and death of liveborn infant before hospital discharge severe respiratory disease, severe intraventricular haemorrhage (grade 3 & 4); chronic lung disease (oxygen dependent at 36 weeks post-menstrual age); proven necrotising enterocolitis; severe retinopathy of prematurity (Stage 3 or worse in the better eye); cystic periventricular leukomalacia).
Timepoint [2] 273297 0
Up to hospital discharge.
Secondary outcome [3] 273298 0
Individual components of the primary outcome including severity of cerebral palsy (defined as death, cerebral palsy).
Timepoint [3] 273298 0
2 years' corrected age.
Secondary outcome [4] 273299 0
Death or any neurosensory disability (death defined as stillbirth, death of live born infant before hospital discharge or death after hospital discharge; and any neurosensory disabilities that includes the neurosensory impairments of cerebral palsy, [GMFCS level 1 to 5], blindness [corrected visual acuity worse than 6/60 in the better eye], deafness [hearing loss requiring amplification or worse], and any developmental delay defined as standardised score more than 1 SD below the mean (< -1SD).
Timepoint [4] 273299 0
At 2 years' corrected age.
Secondary outcome [5] 276175 0
Death or major neurosensory disability Major neurosensory disability includes severe and moderate disability (defined as any of: legal blindness, sensorineural deafness requiring hearing aids; moderate or severe cerebral palsy [GMFCS level 2 to 5] or developmental delay/intellectual impairment [standardised score more than two SD below the mean].
Timepoint [5] 276175 0
At 2 years' corrected age.
Secondary outcome [6] 276176 0
General health of the child (including use of health services since primary hospitalisation), childhood respiratory morbidity, blood pressure (Z scores and proportions in hypertensive ranges), and behaviour as assessed by the Child Behaviour Checklist (Achenbach 1992) and Body size.
Timepoint [6] 276176 0
At 2 years' corrected age.
Secondary outcome [7] 276177 0
Maternal serious adverse cardiovascular and/or respiratory outcome of the infusion (defined as maternal death, cardiac arrest, respiratory arrest).
Timepoint [7] 276177 0
At time of trial treatment infusion.
Secondary outcome [8] 276262 0
Maternal side effects of the infusion (including nausea; vomiting; flushing, infusion arm discomfort; mouth dryness; sweating; dizziness; blurred vision; respiratory rate decreased >4 breaths per minute below baseline or <12 breaths per minute; blood pressure decreased >15 mm Hg below baseline level; whether the infusion is discontinued because of side effects).
Timepoint [8] 276262 0
At time of trial treatment infusion.
Secondary outcome [9] 296345 0
Incidence of postpartum haemorrhage, estimated blood loss at birth 500 mL or more; and major postpartum haemorrhage, estimated blood loss 1500 mL or more.
Mode of birth
Timepoint [9] 296345 0
At time of birth.

Eligibility
Key inclusion criteria
Women are eligible for the trial if they are at risk of preterm birth between 30 and 34 weeks’ gestation where birth is planned or definitely expected within 24 hours, have a singleton or twin pregnancy, no contraindications to the use of antenatal magnesium sulphate (myasthenia gravis, respiratory depression, hypotension, absent patellar reflexes or renal failure) and give informed, written consent.
Minimum age
16 Years
Maximum age
50 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Women are not eligible if they have a higher-order multiple pregnancy, have already received antenatal magnesium sulphate or if magnesium sulphate therapy is considered essential for the treatment of pre-eclampsia.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible women are counselled and give signed, informed consent prior to enrolment. Trial entry details are obtained from the woman's casenotes and eligibility is confirmed. The woman is enrolled by contacting the central telephone randomisation service at the University of Adelaide. Random assignment to one of two groups: either the 'magnesium sulphate group' or the 'placebo group'. A Study Number and a corresponding numbered treatment pack will be allocated.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation schedule will use balanced variable blocks and will be created using computerise sequence generation by researchers not involved in clinical care, recruitment, data collection and follow-up assessment. Assignment to treatment group will be stratified for collaborating centre, gestational age (30 to 31 completed weeks; 32-33 completed weeks’ gestation), and number of fetuses (1 or 2).
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)
Safety/efficacy

Recruitment
Anticipated date of first participant enrolment
30/01/2012
Actual date of first participant enrolment
31/01/2012
Anticipated date last participant enrolled
Actual date last participant enrolled
Anticipated date of last data collection
Actual date of last data collection
Target sample size
1676
Actual sample size
Recruitment status
Recruiting
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC
Recruitment outside Australia
Country [1] 5926 0
New Zealand
State/province [1] 5926 0

Funding & Sponsors
Funding source category [1] 258550 0
Government body
Name [1] 258550 0
National Health and Medical Research Council (NHMRC)
Address [1] 258550 0
Physical address:
Level 5,20 Allara Street
Canberra ACT, 2601

Postal address:
GPO Box 1421
Canberra ACT, 2601
Country [1] 258550 0
Australia
Primary sponsor type
University
Name
University of Adelaide
Address
North Tce
Adelaide South Australia 5005
Country
Australia
Secondary sponsor category [1] 257684 0
None
Name [1] 257684 0
Address [1] 257684 0
Country [1] 257684 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260518 0
Children, Youth & Women's Health Service (CYWHS) Human Research Ethics Committee (HREC)
Ethics committee address [1] 260518 0
Children, Youth & Women's Health Service (Women's and Children's Hospital),
72 King William Road,
North Adelaide SA 5006
Ethics committee country [1] 260518 0
Australia
Date submitted for ethics approval [1] 260518 0
Approval date [1] 260518 0
31/10/2011
Ethics approval number [1] 260518 0
REC 2303/8/13
Ethics committee name [2] 286812 0
Royal Children's Hospital Health Service District HREC
Ethics committee address [2] 286812 0
Royal Children's Hospital (Brisbane)
Department of Paediatrics & Child Health
Level 3 Foundation Building
Herston Rd
Herston Qld 4029
Ethics committee country [2] 286812 0
Australia
Date submitted for ethics approval [2] 286812 0
Approval date [2] 286812 0
18/01/2012
Ethics approval number [2] 286812 0
HREC 11/QRCH/181
Ethics committee name [3] 290782 0
Human Research Ethics Committee (Tasmania) Network
Ethics committee address [3] 290782 0
University of Tasmania
Private Bag 1
Hobart Tasmania 7001
Ethics committee country [3] 290782 0
Australia
Date submitted for ethics approval [3] 290782 0
14/06/2012
Approval date [3] 290782 0
12/09/2012
Ethics approval number [3] 290782 0
H0012653
Ethics committee name [4] 290783 0
Northern B Health & Disability Ethics Committee
Ethics committee address [4] 290783 0
Ministry of health
c/- MEDSAFE, Level 6 Deloitte House
10 Brandon St
Wellington 6011
Ethics committee country [4] 290783 0
New Zealand
Date submitted for ethics approval [4] 290783 0
18/05/2012
Approval date [4] 290783 0
06/09/2012
Ethics approval number [4] 290783 0
LRS/12/06/021

Summary
Brief summary
Antenatal magnesium sulphate is recommended prior to preterm birth at less than 30 weeks’ gestation for neuroprotection of the fetus. Whether there are benefits at later gestations is uncertain. The primary aim of this randomised placebo controlled trial is to assess whether giving magnesium sulphate compared with placebo to women immediately prior to preterm birth between 30 and 34 weeks' gestation reduces the risks of death or cerebral palsy in their children at 2 years' corrected age. years' corrected age.
Trial website
http://www.adelaide.edu.au/arch/research/clinical_trials/magenta
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32256 0
Prof Caroline Crowther
Address 32256 0
Australian Research Centre for Health of Women and Babies (ARCH), The Robinson Research Institute, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Women's and Children's Hospital, King William Road, North Adelaide SA 5006
Country 32256 0
Australia
Phone 32256 0
+61 8161 7619
Fax 32256 0
+61 8 8161 7652
Email 32256 0
caroline.crowther@adelaide.edu.au
Contact person for public queries
Name 15503 0
Ms Pat Ashwood
Address 15503 0
Australian Research Centre for Health of Women and Babies (ARCH), The Robinson Research Institute, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Women's and Children's Hospital, King William Road, North Adelaide SA 5006
Country 15503 0
Australia
Phone 15503 0
+61 8 8161 7767
Fax 15503 0
+61 8 8161 7652
Email 15503 0
pat.ashwood@adelaide.edu.au
Contact person for scientific queries
Name 6431 0
Prof Caroline Crowther
Address 6431 0
Australian Research Centre for Health of Women and Babies (ARCH), The Robinson Research Institute, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Women's and Children's Hospital, King William Road, North Adelaide SA 5006
Country 6431 0
Australia
Phone 6431 0
+61 8 8161 7619
Fax 6431 0
+61 8 8161 7652
Email 6431 0
caroline.crowther@adelaide.edu.au