Condition category
Pregnancy and Childbirth
Date applied
23/05/2016
Date assigned
06/07/2016
Last edited
01/11/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Pre-eclampsia (PE) is a medical condition which can develop during pregnancy, and can affect both the mother and unborn baby. In PE, it is thought that the blood supply to the placenta (organ which connects the mother and child’s blood supply) is reduced, which can mean the unborn baby does not get enough nutrients to develop properly. The key indicators of PE are high blood pressure and protein in the mother’s urine. The National Institute for Health and Clinical Excellence (NICE) recommends that the way to determine whether a woman is at high-risk of developing pre-eclampsia should depend on maternal risk factors. However, this method of screening only identifies about 40% of the women that develop pre-eclampsia requiring delivery before 37 weeks and 35% of all cases of pre-eclampsia. This study uses a new method of screening called the Bayes method that combines maternal risk factors with the results from various tests to calculate the individual risk for developing pre-eclampsia. Extensive research in the last decade has led to the identification of four potentially useful tests: measurements of blood pressure, blood flow in the maternal blood vessels that supply the womb and the levels of two placental hormones in the mother’s blood. There is some evidence that the new test used in this study is superior to that of NICE method. The aim of the study is to evaluate the effectiveness of this new method of screening for pre-eclampsia against that currently recommended by NICE.

Who can participate?
Pregnant women aged 18 years or over with a live fetus at 11-13 weeks pregnancy.

What does the study involve?
Women attend two study visits, one when they are 11-13 weeks pregnant and one when they are 19-24 weeks pregnant. At the first study visit, women have their weight and height recorded as well as their medical history. They then have a special ultrasound scan to measure the blood flow in the vessels that supply the womb and have samples of blood taken which are tested for placental hormones. At the second study visit, routine data is collected during the participants scan. The information collected at these visits is then used to make predictions about whether the women will develop pre-eclampsia. Women then have their medical records reviewed up to one month after they have had their baby to find out which screening method is most accurate.

What are the possible benefits and risks of participating?
There are no direct benefits or risks involved with participating in this study.

Where is the study run from?
King’s College Hospital (lead centre) and six other hospitals in England (UK)

When is the study starting and how long is it expected to run for?
October 2015 to July 2018

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Dr Kate Maclagan
k.maclagan@ucl.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Kate Maclagan

ORCID ID

Contact details

Comprehensive Clinical Trials Unit
University College London
Gower Street
London
WC1E 6BT
United Kingdom
+44 20 3549 5015
k.maclagan@ucl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

20412

Study information

Scientific title

The diagnostic accuracy of pregnant women screened for pre-eclampsia using Bayes theorem based and screening according to NICE guidelines

Acronym

SPREE

Study hypothesis

The aim of this study is to compare screening for pre-eclampsia (PE) using a Bayes theorem based method with screening using current NICE guidelines.

Ethics approval

London- Surrey Borders Research Ethics Committee, 22/12/2015, ref: 15/LO/2161

Study design

Observational diagnostic accuracy cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Reproductive health and childbirth, Primary sub-specialty: Reproductive and sexual medicine

Intervention

All participants to attend the 2 study visits (at 11-13 weeks gestation and 19-24 weeks gestation). The final, pregnancy outcome data is retrieved from patient notes so no participant visit is required.

At the first study visit women will give informed consent, and data will be collected on patient demographics, height and weight, maternal medical and obstetric history, family history, drug history including aspirin intake, routine first-trimester scan, mean arterial pressure, uterine artery blood flow( pulsatility index) via transabdominal colour Doppler ultrasound. Blood samples will also be collected to measure for biomarkers serum placental growth factor (PlGF) and serum pregnancy associated plasma protein-A (PAPP-A). All these data will then be used for the risk calculation to determine the risk of preeclampsia using the Bayes theorem method.

At the second study visit at 19-24 weeks a routine anomaly scan will be carried out and routine data associated with this scan will be collected.

The incidence of pre-eclampsia is ascertained via data collected at 11-13 weeks gestation and 19-24 weeks gestation at routine visits and from pregnancy outcome data in patient notes collected within one month of giving birth.

Of these data, only data from all participants that developed pre-eclampsia (PE) will be analysed to test the diagnostic accuracy of both the Bayes theorem method (mini combined and combined) prediction compared to the NICE guidelines prediction (retrospectively).

The Bayes theorem combined test requires the following data: combination of maternal characteristics and medical history together with the measurements of the mean arterial pressure (MAP), uterine artery pulsatility index (PI), serum placental growth factor (PlGF) and serum pregnancy associated plasma protein-A (PAPP-A) at 11-13 weeks’ gestation.

The Bayes theorem mini combined test requires the following data: A combination of maternal characteristics and medical history, MAP and PAPP-A

The NICE Guidelines for diagnosis of risk of PE requires review of the data which will be retrieved from patient notes collected at 11-13 weeks.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Diagnostic accuracy (false positive and true positive frequencies) of screening for pre-eclampsia using the Bayes theorem based method is measured as the rate of pre-eclampsia, determined using medical note review within one month of birth.

Secondary outcome measures

Detection rate of pre-eclampsia is measured through medical note review within one month of birth.

Overall trial start date

04/10/2015

Overall trial end date

31/07/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 18 or over
2. Singleton pregnancy
3. Live fetus at 11-13 weeks' gestation
4. Informed and written consent

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 16850; UK Sample Size: 16850

Participant exclusion criteria

1. Women who are severely ill
2. Those with learning difficulties
3. Those with a serious mental illness
4. Pregnancies complicated by major fetal abnormality identified at 11-13 weeks of gestation

Recruitment start date

12/04/2016

Recruitment end date

31/01/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

King’s College Hospital
Harris Birthright Centre Fetal Medicine Research Institute 16-20 Windsor Walk
London
SE5 8BB
United Kingdom

Trial participating centre

Medway Maritime Hospital
Fetal Medicine Unit Windmill Road
Gillingham
ME7 5NY
United Kingdom

Trial participating centre

North Middlesex Hospital
Gynaecology, Maternity Building Level 1 North Middlesex University Hospital NHS Trust Sterling Way
London
N18 1QX
United Kingdom

Trial participating centre

Homerton University Hospital
Fetal Medicine Unit 2nd floor Antenatal Clinic Homerton Row
London
E9 6SR
United Kingdom

Trial participating centre

Southend University Hospital
Southend University Hospital NHS Foundation Trust Kypros Nicolaides Fetal Medicine Centre 2nd Floor Cardigan Building Prittlewell Chase
Westcliff on sea
SS0 0RY
United Kingdom

Trial participating centre

University Hospital Lewisham
UItrasound Room 5 Ground Floor Women's Health Green Zone Lewisham High Street Lewisham
London
SE13 6LH
United Kingdom

Trial participating centre

The Royal London Hospital
The Fetal Medicine Centre Ward 8E, 8th floor, South Tower Whitechapel road
London
E1 1BB
United Kingdom

Sponsor information

Organisation

Delegated to University College London Comprehensive Clinical Trials Unit (UCL CCTU) by Kings College London

Sponsor details

Comprehensive Clinical Trials Unit
Gower Street
London
WC1E 6BT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in peer reviewed journals an presentation at relevant meetings.

Intention to publish date

11/07/2018

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

01/11/2016: The following changes have been made to the record: 1. A fourth exclusion criterion has been added 2. The overall trial end date has been updated from 11/07/2017 to 31/07/2018 3. An additional trial participating centre has been added