Low dose aspirin with an early screening test for pre-eclampsia and fetal growth restriction

ISRCTN	ISRCTN15191778
DOI	https://doi.org/10.1186/ISRCTN15191778
ClinicalTrials.gov (NCT)	NCT03674606
Clinical Trials Information System (CTIS)	2013-004241-17
Protocol serial number	TEST_PILOT_V1
Sponsor	University College Dublin (Ireland)
Funder	Perinatal Ireland (Ireland)

Submission date: 08/01/2014
Registration date: 10/02/2014
Last edited: 13/02/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Pregnancy and Childbirth

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Pre-eclampsia is a condition that affects 2-8% of pregnancies. Previous studies have shown that aspirin can reduce the occurrence of pre-eclampsia in women with known risk factors but we know little for low risk populations. This study aims to assess if it is beneficial in terms of effectiveness and patient acceptability to routinely prescribe low dose aspirin to low risk women on the basis of a positive early pregnancy screening test for pre-eclampsia and fetal growth restriction. The specific aims of this study are:
1. Number of eligible women who agree to participate in the study.
2. Adherence to the study methodology
3. Number of women in whom it was possible to get first trimester abdominal uterine artery Doppler examination
4. Number of women with completed screening test who are issued the screening result on time

Who can participate?
Women who are expecting their first baby, less than 14 weeks pregnant at their first visit, not on aspirin

What does the study involve?
500 first time mothers with low-risk pregnancies will be randomly allocated to one of three groups from early pregnancy:
Group 1 will receive 75mg of aspirin until 36 weeks
Group 2 will not receive aspirin
Group 3 will receive 75mg of aspirin until 36 weeks only if they screen positive using the Fetal Medicine Foundation (FMF) early pregnancy screening test for pre-eclampsia and fetal growth restriction prediction. If this screening test is negative, group 3 will not receive aspirin.
All participants will undergo these first trimester screening tests but the results will only be given for group 3.

What are the possible benefits and risks of participating?
Benefits include detailed scans performed of the baby in the first and second trimester of pregnancy as well as monitoring of blood pressure. Mothers involved in the study will be contributing to a study which has the potential to significantly reduce the occurrence of pregnancy complications such as pre-eclampsia and fetal growth restriction which risks the lives of mothers and babies worldwide. Studies have shown that low dose aspirin appear to be safe for mother and baby, it is a medication frequently used by mothers who are at high risk of developing pre-eclampsia.

Where is the study run from?
The study will run from the National Maternity Hospital, Coombe Maternity Hospital and Rotunda Maternity Hospital, Dublin, Ireland.

When is the study starting and how long is it expected to run for?
The trial is starting in February 2014 and is expected to run for two years.

Who is funding the study?
Perinatal Ireland Consortium (Ireland)

Who is the main contact?
Professor Fionnuala McAuliffe
fionnuala.mcauliffe@ucd.ie

Contact information

Prof Fionnuala McAuliffe
Scientific

UCD Obstetrics & Gynaecolgy
School of Medicine and Medical Science
University College Dublin
National Maternity Hospital
Dublin
Dublin 2
Ireland

Phone	+353 (0)637 3216
Email	fionnuala.mcauliffe@ucd.ie

Study information

Primary study design	Interventional
Study design	Multicentre randomized controlled open-labelled pilot trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	An open-label randomized-controlled trial of low dose aspirin with an early screening test for pre-eclampsia and fetal growth restriction: a pilot study
Study objectives	The hypothesis of this study is to assess if it is beneficial in terms of efficacy and patient acceptability to routinely prescribe low dose aspirin to nulliparous low risk women compared with test indicated aspirin on the basis of a positive early pregnancy screening test for pre-eclampsia and fetal growth restriction.
Ethics approval(s)	National Maternity Hospital, Dublin, Ireland, 11/11/2013
Health condition(s) or problem(s) studied	Pregnancy/pre-eclampsia/fetal growth restriction
Intervention	Following assessment for study eligibility at time of antenatal booking in the first trimester, women will undergo computer-generated randomisation to one of 3 antenatal management protocols: 1. Aspirin therapy 75mg daily commencing after a satisfactory1st trimester assessment, followed by a mid-trimester assessment and routine antenatal care thereafter (routine aspirin arm) 2. No aspirin therapy with 1st trimester assessment, mid-trimester assessment and routine antenatal care thereafter (control arm) 3. Postponement of decision regarding aspirin therapy until availability of the Fetal Medicine Foundation screening result for pre-eclampsia risk at time of 1st trimester assessment, with immediate commencement of aspirin 75mg daily in the screen positive subgroup, set at a false positive rate of 5% (screen & treat arm) Assessment at the first trimester visit will include: 1. Assessment of blood pressure 2. Ultrasound scan: uterine artery doppler measurements 3. Blood tests: placental biomarkers to determine pre-eclampsia risk The routine aspirin arm and those with a screen positive in the screen and treat arm will receive Aspirin 75mg from first trimester until 36 weeks of pregnancy and all participants will be asked to return for a visit at 20-22 weeks of pregnancy which will involve: 1. Blood pressure 2. Repeating the blood tests for placental biomarkers 3. Performing an ultrasound of fetal anatomy and uterine artery doppler assessment Women will then attend for routine antenatal care until delivery
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Aspirin
Primary outcome measure(s)	1. Proportion of eligible women who agree to participate in the pilot study. This will be calculated by the % of women who agree to study participation out of all those eligible women who were approached for study participation after written consent has been obtained in the first trimester. 2. Compliance with the study protocol. This will be measured at 20 week with a compliance questionnaire for those prescribed aspirin 75mg. 3. Proportion of women in whom it was possible to obtain first trimester trans-abdominal uterine artery Doppler examination. This will be assessed at the first trimester visit. 4. Proportion of women with completed screening test who are issued the screening result on time. This will be assessed as the % of women who received a result of the screening test within one week of having the test performed in the screen and treat group (group 3)
Key secondary outcome measure(s)	1. Rate of pre-eclampsia. This is defined as those with BP 140/90 with +1 proteinuria at any time in pregnancy. 2. Rate of fetal intrauterine growth restriction (IUGR), defined as birth-weight <10th centile for gestational age 3. Spontaneous or iatrogenic delivery at <34 and < 37 completed weeks. 4. Rate of admission to the neonatal intensive care unit 5. Rate of placental abruption, any reported death (stillbirth, neonatal or infant death) and small for gestational age infants 6. Patient acceptability will be assessed with a questionnaire at 34 weeks gestation
Completion date	13/04/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target sample size at registration	500
Total final enrolment	546
Key inclusion criteria	1. Women who are in their first pregnancy 2. Women who are able to speak and read English so that they can provide consent to be included in the study 3. Women who have a singleton pregnancy below 14 weeks
Key exclusion criteria	1. Presence of fetal abnormality at the time of the first trimester scan 2. Women with known risk factors for pre-eclampsia or growth restricted babies who may already be on Aspirin for this reason 3. Women already taking part in another study 4. Women who cannot take Aspirin 5. Women aged under 18 years
Date of first enrolment	08/05/2014
Date of final enrolment	01/02/2016

Locations

Countries of recruitment

Ireland

Study participating centre

UCD Obstetrics & Gynecology

Dublin
Dublin 2
Ireland

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	28/07/2018		Yes	No
Protocol article	protocol	01/07/2016	13/02/2020	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

13/02/2020: ClinicalTrials.gov number, publication reference and total final enrolment number added.
30/07/2018: Publication reference added.
07/12/2016: The overall trial end date has been updated from the anticipated end date of 01/02/2016 to actual end of date of 13/04/2016 and the anticipated start date of 01/02/2014 has been updated to actual recruitment start date of 08/05/2014.