Trial registered on ANZCTR


Trial ID
ACTRN12607000551493
Ethics application status
Approved
Date submitted
18/10/2007
Date registered
26/10/2007
Type of registration
Retrospectively registered

Titles & IDs
Public title
Screening for pregnancy endpoints: preeclampsia, growth restricted baby and spontaneous preterm birth.
Scientific title
Screening nulliparous women to identify the combinations of clinical risk factors and/or biomarkers required to predict preeclampsia, small for gestational age babies and spontaneous preterm birth.
Secondary ID [1] 288321 0
Nil known
Universal Trial Number (UTN)
Trial acronym
SCOPE; (Also known in the in the United Kingdom as MAPS in Ireland as SCOPE Ireland).

Health condition
Health condition(s) or problem(s) studied:
Preeclampsia. 2319 0
Small for gestational age babies (SGA). 2320 0
Spontaneous preterm birth. 2321 0
Condition category
Condition code
Reproductive Health and Childbirth 2422 2422 0 0
Fetal medicine and complications of pregnancy
Reproductive Health and Childbirth 297482 297482 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Prospective cohort, with case cohort design. The cohort comprises nulliparous women with a singleton pregnancy in New Zealand, Australia, United Kingdom and Ireland who are prospectively studied from 14 weeks gestation to postpartum. Cases are women who develop one or more of the following conditions: preeclampsia, an SGA baby or spontaneous preterm birth. For all secondary endpoints the cases will be women with the secondary endpoint of interest.
Data on all known risk factors for preeclampsia, spontaneous preterm birth and SGA are collected at 15+/-1 and 20 +/-1 weeks’ gestation by interview and examination of the women. Blood and urine specimens are obtained at both time points, with a high vaginal swab taken at the 20 week visit. Additional information is collected about diet, lifestyle, stress, depression and other mood disorders. Ultrasound data are obtained at 20 weeks on fetal measurements, anatomy, uterine and umbilical artery Doppler and cervical length. Fetal growth, uterine and umbilical Dopplers are measured at 24 weeks. Pregnancy outcome is tracked and the woman seen within 48 hours of delivery. Baby measurements are obtained within 48 hours of delivery.
Proteomic, targeted genomic and metabolomic studies are being performed to identify biomarkers, which will then be evaluated and validated as screening tests by using quantitative, high throughput methods (such as multiplex immunoassay) to measure specific analytes in the cohort. These data will then be used to develop predictive algorithms based on clinical risk factors alone, biomarkers alone or combinations of both.
Intervention code [1] 2039 0
Early detection / Screening
Comparator / control treatment
In the main cohort study, when the outcome is preeclampsia, controls are women without preeclampsia. For SGA, controls are women without SGA. For spontaneous preterm birth, controls are women without spontaneous preterm birth. A case cohort design will be used when investigating prediction based on blood biomarkers, with controls comprising women randomly selected from the non-disease groups described above.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 3319 0
Preeclampsia defined as gestational hypertension (systolic blood pressure (BP) >= 140 mmHg and/or diastolic BP >= 90mmHg (Korotkoff V) on at least 2 occasions 4 hours apart after 20 weeks gestation but before the onset of labour) or postpartum systolic BP >= 140 mmHg and/or diastolic BP >= 90mmHg postpartum on at least 2 occasions 4 hours apart with proteinuria >= 300 mg/24h or spot urine protein: creatinine ratio >=30 mg/mmol creatinine or urine dipstick protein >= ++ or any multi-system complication of preeclampsia.
Multisystem complications include any of the following:
1. Acute renal insufficiency defined as a new increase in serum creatinine >=100 umol/L antepartum or >130 umol/L postpartum
2. Liver disease defined as raised aspartate transaminase and/or alanine transaminase >45 IU/L and/or severe right upper quadrant or epigastric pain or liver rupture
3. Neurological problems defined as eclampsia or imminent eclampsia (severe headache with hyperreflexia and persistent visual disturbance) or cerebral haemorrhage
4. Haematological including thrombocytopenia (platelets <100 x 109/L), disseminated intravascular coagulation or haemolysis, diagnosed by features on blood film (e.g., fragmented cells, helmet cells) and reduced haptoglobin.
Timepoint [1] 3319 0
At any stage during pregnancy after recruitment until delivery or in the first 2 weeks after delivery.
Primary outcome [2] 3320 0
SGA defined as: birthweight <10th% using customized centiles, adjusted for maternal weight, height, parity, ethnicity and infant sex.
Timepoint [2] 3320 0
First 24 hours after baby's birth.
Primary outcome [3] 3321 0
Spontaneous preterm birth defined as spontaneous preterm labour or preterm premature rupture of the membranes (PPROM) resulting in preterm birth at <370 weeks.
Timepoint [3] 3321 0
When the mother has given birth to the baby.
Secondary outcome [1] 5530 0
Early onset preeclampsia defined as preeclampsia resulting in delivery at <340 weeks.
Timepoint [1] 5530 0
At any stage during pregnancy after recruitment until delivery or in the first 2 weeks after delivery.
Secondary outcome [2] 5531 0
Preeclampsia with severe fetal or neonatal complications defined as preeclampsia resulting in either delivery at <320 weeks or major neonatal morbidity or stillbirth or neonatal death or post-neonatal death. Preterm major neonatal morbidity is defined as one or more of the following amongst babies delivered before 37 weeks: Grade III or IV intraventricular haemorrhage, chronic lung disease, necrotizing enterocolitis, retinopathy of prematurity stage 3 or 4, sepsis (blood or CSF culture proven) or cystic peri-ventricular leukomalacia. These conditions will be defined using the Australian and New Zealand neonatal network definitions. Term major neonatal morbidity is defined as one or more of the following amongst babies delivered at or after 37 weeks gestation: Grade II or III hypoxic ischemic encephalopathy, ventilation>24 hours, neonatal unit admission >4 days, Apgars <4 at 5 mins, cord arterial pH<7.0 and/or base excess >-15 or neonatal seizures.
Timepoint [2] 5531 0
When the mother has given birth to the baby or at the time of baby death or baby discharge from the neonatal nursery.
Secondary outcome [3] 5532 0
Preeclampsia with severe maternal complications defined as the development of preeclampsia with one or more of the following: maternal death, persistent severe hypertension (systolic blood pressure >=170 mmHg or diastolic blood pressure >=110 mmHg on more than one occasion antepartum or postpartum) or multi-system complication as defined above.
Timepoint [3] 5532 0
At any stage during pregnancy after recruitment until delivery or in the first 2 weeks after delivery.
Secondary outcome [4] 5803 0
Preeclampsia with either severe maternal complication or severe fetal or neonatal complications includes all preeclamptic pregnancies affected by severe maternal or severe fetal or neonatal complications as defined above.
Timepoint [4] 5803 0
Preeclampsia with severe maternal complications: at any stage during pregnancy after recruitment until delivery or in the first 2 weeks after delivery. Preeclampsia with severe fetal or neonatal complications: When the mother has given birth to the baby or at the time of baby death or baby discharge from the neonatal nursery.
Secondary outcome [5] 5804 0
Early onset SGA defined as birthweight <10th customised centile resulting in delivery at <340 weeks.
Timepoint [5] 5804 0
First 24 hours after baby's birth.
Secondary outcome [6] 5805 0
SGA with severe fetal or neonatal complications defined as SGA and either delivery at <320 weeks or major neonatal morbidity or stillbirth or neonatal death or post-neonatal death. Preterm major neonatal morbidity is defined as one or more of the following amongst babies delivered before 37 weeks: Grade III or IV intraventricular haemorrhage, chronic lung disease, necrotizing enterocolitis, retinopathy of prematurity stage 3 or 4, sepsis (blood or CSF culture proven) or cystic peri-ventricular leukomalacia. These conditions will be defined using the Australian and New Zealand neonatal network definitions. Term major neonatal morbidity is defined as one or more of the following amongst babies delivered at or after 37 weeks gestation: Grade II or III hypoxic ischemic encephalopathy, ventilation>24 hours, neonatal unit admission >4 days, Apgars <4 at 5 mins, cord arterial pH<7.0 and/or base excess>-15 or neonatal seizures.
Timepoint [6] 5805 0
When the mother has given birth to the baby or at the time of baby death or baby discharge from the neonatal nursery.
Secondary outcome [7] 5806 0
Early onset spontaneous preterm birth defined as spontaneous preterm labour or PPROM resulting in delivery at <340 weeks.
Timepoint [7] 5806 0
When the mother has given birth to the baby.
Secondary outcome [8] 5807 0
Spontaneous preterm birth with severe fetal or neonatal complications defined as spontaneous preterm labour or PPROM resulting in either delivery at <320 weeks or spontaneous preterm birth resulting in major neonatal morbidity or stillbirth or neonatal death or post-neonatal death. Preterm major neonatal morbidity is defined as one or more of the following amongst babies delivered before 37 weeks Grade III and IV intraventricular haemorrhage, chronic lung disease, necrotizing enterocolitis, retinopathy of prematurity, stage 3 or 4, sepsis (blood or CSF culture proven) or cystic peri-ventricular leukomalacia. These conditions will be defined using the Australian and New Zealand neonatal network definitions.
Timepoint [8] 5807 0
When the mother has given birth to the baby or at the time of baby death or baby discharge from the neonatal nursery.
Secondary outcome [9] 5808 0
9: Spontaneous preterm birth with PPROM defined as preterm birth at <370 weeks following PPROM.
Timepoint [9] 5808 0
When the mother has given birth to the baby.
Secondary outcome [10] 5809 0
10: Spontaneous preterm birth without PPROM defined as spontaneous preterm labour with intact membranes resulting in preterm birth at <370 weeks preterm birth.
Timepoint [10] 5809 0
When the mother has given birth to the baby.
Secondary outcome [11] 319915 0
Gestational Diabetes Mellitus (GDM) defined by the local criteria at each participating center.
Timepoint [11] 319915 0
At any stage during pregnancy after recruitment until delivery.

Eligibility
Key inclusion criteria
Nulliparous women, with a singleton pregnancy, between 14wks 0 days and 16wks 6 days gestation who give informed consent to participate in SCOPE.
Minimum age
No limit
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria: Unsure of last menstrual period (LMP) and unwilling to have ultrasound scan at <= 20 weeks, > =3 miscarriages, >=3 terminations, major fetal anomaly/abnormal karyotype, essential hypertension treated pre-pregnancy, moderate-severe hypertension at booking >=160/100 mmHg, diabetes, renal disease, systemic lupus erythematosus, anti-phospholipid syndrome, sickle cell disease, HIV positive, major uterine anomaly, cervical suture, knife cone biopsy, ruptured membranes now, long term steroids, treatment low-dose aspirin, treatment calcium (>1g/24h), treatment eicosopentanoic acid (fish oil), treatment vitamin C >=1000mg & Vit E >=400iu, treatment heparin/low molecular weight heparin.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Anticipated date of first participant enrolment
11/11/2004
Actual date of first participant enrolment
11/11/2004
Anticipated date last participant enrolled
Actual date last participant enrolled
8/02/2011
Anticipated date of last data collection
Actual date of last data collection
Target sample size
7500
Actual sample size
5690
Recruitment status
Completed
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 5036 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment postcode(s) [1] 467 0
5112
Recruitment outside Australia
Country [1] 584 0
New Zealand
State/province [1] 584 0
Country [2] 585 0
United Kingdom
State/province [2] 585 0
Country [3] 586 0
Ireland
State/province [3] 586 0

Funding & Sponsors
Funding source category [1] 2582 0
Government body
Name [1] 2582 0
Foundation of Research Science and Technology
Address [1] 2582 0
PO Box 12-240
Wellington
Country [1] 2582 0
New Zealand
Funding source category [2] 2717 0
Government body
Name [2] 2717 0
Health Research Council
Address [2] 2717 0
PO Box 5541
Wellesley St
Auckland
Country [2] 2717 0
New Zealand
Funding source category [3] 2718 0
Hospital
Name [3] 2718 0
Evelyn Bond Charitable Fund
Address [3] 2718 0
Auckland District Health Board
PO Box 26-417
Epsom
Auckland
Country [3] 2718 0
New Zealand
Funding source category [4] 2719 0
Government body
Name [4] 2719 0
South Australia Premier Science and Research Fund
Address [4] 2719 0
GPO Box 2343
Adelaide SA 5001
Country [4] 2719 0
Australia
Funding source category [5] 2720 0
Charities/Societies/Foundations
Name [5] 2720 0
Guys and St Thomas' Charity
Address [5] 2720 0
The Counting House Guy's Hospital
1st Floor
St Thomas St
London SE1 9RT
Country [5] 2720 0
United Kingdom
Funding source category [6] 2721 0
Government body
Name [6] 2721 0
Health Research Board Ireland
Address [6] 2721 0
73 Lower Baggot St
Dublin 2
Country [6] 2721 0
Ireland
Funding source category [7] 2722 0
University
Name [7] 2722 0
University of Manchester Proof of Concept Funding UK
Address [7] 2722 0
University of Manchester
Hathersage Rd
Manchester M13 0JH
Country [7] 2722 0
United Kingdom
Funding source category [8] 2723 0
Government body
Name [8] 2723 0
Biotechnology and Biological Sciences Research Council UK
Address [8] 2723 0
Polaris House
North Star Ave
Swindon SN2 1UH
Country [8] 2723 0
United Kingdom
Funding source category [9] 2724 0
Government body
Name [9] 2724 0
National Health Services NEAT Grant UK -Grant
Address [9] 2724 0
National Institute for Health Research
Rm 132
Richmond Hse
79 Whitehall
London SW1A 2NL
Country [9] 2724 0
United Kingdom
Funding source category [10] 2725 0
Charities/Societies/Foundations
Name [10] 2725 0
Tommy's the Baby Charity UK
Address [10] 2725 0
109 High Street
Thame
Oxon OX9 3DZ
Country [10] 2725 0
United Kingdom
Funding source category [11] 2726 0
Charities/Societies/Foundations
Name [11] 2726 0
Cerebra
Address [11] 2726 0
Cerebra
2nd Floor Offices
The Lyric Bldg
King St
Carmarthen SA31 1BD
Country [11] 2726 0
United Kingdom
Funding source category [12] 292688 0
Government body
Name [12] 292688 0
Health Research Board
Address [12] 292688 0
Grattan House, 67-72 Lower Mount Street, Dublin 2, Ireland
Country [12] 292688 0
Ireland
Primary sponsor type
University
Name
Associate Professor Robyn North
Address
SCOPE Study
Tamaki Campus
University of Auckland
Private Bag 92019
Auckland 1172
Country
New Zealand
Secondary sponsor category [1] 2462 0
University
Name [1] 2462 0
Associate Professor Lesley McCowan
Address [1] 2462 0
SCOPE Study
Tamaki Campus
University of Auckland
Private Bag 92019
Auckland 1172
Country [1] 2462 0
New Zealand
Other collaborator category [1] 25 0
University
Name [1] 25 0
Professor Gustaaf Dekker
Address [1] 25 0
Discipline of Obstetrics and Gynaecology
University of Adelaide
Lyell McEwen Hospital
Haydown Rd
Elizabeth Vale SA 5112
Country [1] 25 0
Australia
Other collaborator category [2] 26 0
University
Name [2] 26 0
Dr Claire Roberts
Address [2] 26 0
Discipline of Obstetrics and Gynaecology
University of Adelaide
SA 5005
Country [2] 26 0
Australia
Other collaborator category [3] 27 0
University
Name [3] 27 0
Professor Philip Baker
Address [3] 27 0
Maternal and Fetal Health Research Unit
University of Manchester
St Mary's Hospital
Whitworth Park M13 0JH
Country [3] 27 0
United Kingdom
Other collaborator category [4] 28 0
University
Name [4] 28 0
Professor Lucilla Poston
Address [4] 28 0
Maternal and Fatal Research Unit
Division of Reproduction and Endocrinology
King's College London
St Thomas' Hospital
London SE1 7EH
Country [4] 28 0
United Kingdom
Other collaborator category [5] 76 0
University
Name [5] 76 0
Professor Andrew Shennan
Address [5] 76 0
Maternal and Fatal Research Unit
Division of Reproduction and Endocrinology
King's College London
St Thomas' Hospital
London SE1 7EH
Country [5] 76 0
United Kingdom
Other collaborator category [6] 77 0
University
Name [6] 77 0
Professor James Walker
Address [6] 77 0
Academic Department of Obstetrics & Gynaecology
University of Leeds
L 9
Gledhow Wing
St James University Hospital
Beckett St
Leeds LS9 7TF
Country [6] 77 0
United Kingdom
Other collaborator category [7] 78 0
University
Name [7] 78 0
Mr Nigel Simpson
Address [7] 78 0
Academic Department of Obstetrics & Gynaecology
University of Leeds
L 9
Gledhow Wing
St James University Hospital
Beckett St
Leeds LS9 7TF
Country [7] 78 0
United Kingdom
Other collaborator category [8] 79 0
University
Name [8] 79 0
Dr Louise Kenny
Address [8] 79 0
Department of Obstetrics and Gynaecology
University College Cork
Cork University Maternity Hospital
Wilton
Cork
Country [8] 79 0
Ireland

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4504 0
Northern X Regional Ethics Committee
Ethics committee address [1] 4504 0
Private Bag 92 522
Wellesley St
Auckland
Ethics committee country [1] 4504 0
New Zealand
Date submitted for ethics approval [1] 4504 0
Approval date [1] 4504 0
23/04/2003
Ethics approval number [1] 4504 0
AKX/02/00/364
Ethics committee name [2] 4505 0
Central Northern Adelaide Health Service, Ethics of Human Research Committee
Ethics committee address [2] 4505 0
Lyell McEwin Hospital
Haydown Rd
Elizabeth Vale
Adelaide SA 5112
Ethics committee country [2] 4505 0
Australia
Date submitted for ethics approval [2] 4505 0
Approval date [2] 4505 0
02/09/2005
Ethics approval number [2] 4505 0
2005082
Ethics committee name [3] 4506 0
South East Multi-centre Research Ethics Committee
St Thomas Hospital Research Ethics Committee
Ethics committee address [3] 4506 0
Aylesford
Kent
Ethics committee country [3] 4506 0
United Kingdom
Date submitted for ethics approval [3] 4506 0
Approval date [3] 4506 0
19/01/2007
Ethics approval number [3] 4506 0
06/MRE01/98
Ethics committee name [4] 4638 0
South East Multi-centre Research Ethics Committee
Central Manchester Research Ethics Committee
Ethics committee address [4] 4638 0
Aylesford
Kent
Ethics committee country [4] 4638 0
United Kingdom
Date submitted for ethics approval [4] 4638 0
Approval date [4] 4638 0
19/01/2007
Ethics approval number [4] 4638 0
06/MRE01/98
Ethics committee name [5] 4639 0
Clinical Research Ethics Committee of the Cork Teaching Hospitals
Ethics committee address [5] 4639 0
Secretariat, Clinical Research Ethics Committee of The Cork Teaching Hospitals
1st Floor
Lancaster Hall
6 Little Hanover Street
Cork
Ethics committee country [5] 4639 0
Ireland
Date submitted for ethics approval [5] 4639 0
01/09/2007
Approval date [5] 4639 0
Ethics approval number [5] 4639 0

Summary
Brief summary
Preeclampsia, spontaneous preterm birth and birth of a small for gestational age (growth restricted) baby are the three major complications of late pregnancy, affecting approximately 19% of first pregnancies. They are a leading cause of maternal morbidity, perinatal morbidity and mortality, neuro-developmental handicap and lifelong health consequences. There are a number of clinical risk factors and biomarkers for these diseases, but currently there are no predictive tests for these conditions. Although no single clinical risk factor or biomarker is a useful predictor, novel combinations of clinical risk factors and/or biomarkers are likely to perform as reliable screening tests for these conditions.
The primary aim of SCOPE is to produce clinically useful screening tests based on 1) clinical risk factors, 2) biomarkers and 3) a combination of clinical risk factors and biomarkers to detect first time mothers at high risk of preeclampsia, spontaneous preterm birth and/or small for gestational age babies.
If successful, this will allow individualised tailoring of antenatal care for future first time mothers and where appropriate, intervention to prevent these conditions. This will empower women and their clinicians to make informed decisions about their care in pregnancy, thereby optimizing the health of mothers and babies.
The first generation of predictive tests based on clinical risk factors and biomarkers alone or in combination with clinical risk factors will be developed in the first 2500 women recruited into SCOPE. The total sample size for further testing and validation is estimated at 10,000.
Trial website
www.scopestudy.net,
www.maps-study.net
Trial related presentations / publications
We have had 62 SCOPE publications - a complete list has been put in as an attachment.
Public notes
Attachments [1] 705 0
http://www.anzctr.org.au/AnzctrAttachments/82254-SCOPE Consortium Publications List_uploaded_ANZCTR_151221.docx

Contacts
Principal investigator
Name 28023 0
Prof Professor Louise Kenny
Address 28023 0
Director, The Irish Centre for Fetal and Neonatal Translational Research
Professor of Obstetrics and Consultant Obstetrician and Gynaecologist
Department of Obstetrics and Gynaecology,
5th Floor, Cork University Maternity Hospital,
Wilton,
Cork,
IRELAND
Country 28023 0
Ireland
Phone 28023 0
+353 (0)21 420 5023
Fax 28023 0
+353 (0)21 420 5025
Email 28023 0
L.Kenny@ucc.ie
Contact person for public queries
Name 11180 0
Prof Professor Louise Kenny
Address 11180 0
Director, The Irish Centre for Fetal and Neonatal Translational Research
Professor of Obstetrics and Consultant Obstetrician and Gynaecologist
Department of Obstetrics and Gynaecology,
5th Floor, Cork University Maternity Hospital,
Wilton,
Cork,
IRELAND
Country 11180 0
Ireland
Phone 11180 0
+353 (0)21 420 5023
Fax 11180 0
+353 (0)21 420 5025
Email 11180 0
L.Kenny@ucc.ie
Contact person for scientific queries
Name 2108 0
Prof Prof Louise Kenny
Address 2108 0
Director, The Irish Centre for Fetal and Neonatal Translational Research
Professor of Obstetrics and Consultant Obstetrician and Gynaecologist
Department of Obstetrics and Gynaecology,
5th Floor, Cork University Maternity Hospital,
Wilton,
Cork,
IRELAND
Country 2108 0
Ireland
Phone 2108 0
+353 (0)21 420 5023
Fax 2108 0
+353 (0)21 420 5025
Email 2108 0
L.Kenny@ucc.ie