Condition category
Pregnancy and Childbirth
Date applied
28/10/2010
Date assigned
12/01/2011
Last edited
01/07/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The placenta (afterbirth) is responsible for providing food and oxygen to the fetus. When there is a problem with the function of the placenta the fetus may not grow well and the mother can develop high blood pressure (pre-eclampsia). Placental problems affect about 10% of pregnancies. The consequences are usually minor but occasionally they can be serious both for the mother and the baby. On the basis of the findings of our tests (blood flow through the uterine arteries, blood pressure, and blood levels of proteins produced by the placenta), we can determine whether a patient is at increased risk of developing pre-eclampsia. The aim of this study to determine giving these patients a low dose of aspirin reduces their risk of pre-eclampsia.

Who can participate?
Pregnant women aged 18 or over who are at a high risk of developing pre-eclampsia

What does the study involve?
Participants are randomly allocated to take either aspirin or a placebo (dummy drug) once per night until 36 weeks’ gestation or when signs of labour commence. All participants are followed up until the last patient has delivered.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
King's College Hospital (UK)

When is the study starting and how long is it expected to run for?
January 2014 to November 2016

Who is funding the study?
European Commission Research: The Seventh Framework Programme (FP7)

Who is the main contact?
Prof Kypros Nicolaides

Trial website

http://www.aspre.eu

Contact information

Type

Scientific

Primary contact

Prof Kypros Nicolaides

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

2013-003778-29

ClinicalTrials.gov number

Protocol/serial number

62340803

Study information

Scientific title

Combined multi-marker screening and randomised patient treatment with ASpirin for evidence-based PRE-eclampsia prevention

Acronym

ASPRE

Study hypothesis

To examine if the prophylactic use of low-dose aspirin from the first-trimester of pregnancy in women at increased risk for preeclampsia can reduce the incidence and severity of the disease.

Ethics approval

NRES Committee London - Fulham, 12/11/2013, REC ref: 13/LO/1479

Study design

Double-blind randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Pre-eclampsia

Intervention

Current interventions as of 21/04/2016:
Randomised participants will be advised to start 150 mg of Aspirin or Placebo once per night within 24 hours of randomisation until 36 weeks’ gestation or when signs of labour commence.
The maximum duration for aspirin or placebo intake will be 180 days.

Interventions from 28/04/2014 to 21/04/2016:
Aspirin 150 mg daily versus placebo. The total duration of treatment is 6 months (from 12 weeks' gestation to 36 weeks) and follow-up for all arms will be up to the last randomised patient has delivered.

Interventions from 12/03/2013 to 28/04/2014:
Aspirin 150 mg daily versus placebo. The total duration of treatment is 5 months (from 12 weeks' gestation to 34 weeks) and follow-up for all arms will be up to the last randomised patient has delivered.

Original interventions until 12/03/2013:
Aspirin 75 mg daily versus placebo. The total duration of treatment is 6 months (from 12 weeks gestation to 36 weeks) and follow-up for all arms will be up to the last randomised patient has delivered.

Intervention type

Drug

Phase

Phase III

Drug names

Aspirin

Primary outcome measures

Current primary outcome measures as of 12/03/2013:
Development of pre-eclampsia, requiring delivery before 37 weeks' gestation

Previous primary outcome measures until 12/03/2013:
Development of pre-eclampsia, measures will be obtained at the end of the pregnancy.

Secondary outcome measures

Current secondary outcome measures as of 21/04/2016:
1. To determine the effect of low-dose aspirin on adverse outcome of pregnancy at <37 weeks
1.1. Pre-eclampsia (PE) requiring delivery at <37 weeks
1.2. Small for gestational age (SGA) (<5th percentile) requiring delivery at <37 weeks
1.3. Miscarriage or stillbirth at <37 weeks
1.4. Placental abruption (clinically or on placental examination) at <37 weeks
1.5. Composite of any of the above
2. To determine the effect of low-dose aspirin on adverse outcome of pregnancy at <34 weeks
2.1. PE requiring delivery at <34 weeks
2.2. SGA (<5th percentile) requiring delivery at <34 weeks
2.3. Miscarriage or stillbirth at <34 weeks
2.4. Placental abruption (clinically or on placental examination) at <34 weeks
2.5. Composite of any of the above
3. To determine the effect of low-dose aspirin on adverse outcome of pregnancy at >37 weeks
3.1. PE requiring delivery at >37 weeks
3.2. SGA (<5th percentile) requiring delivery at >37 weeks
3.3. Miscarriage or stillbirth at >37 weeks
3.4. Placental abruption (clinically or on placental examination) at >37 weeks
3.5. Composite of any of the above
4. To determine the effect of low-dose aspirin on neonatal mortality and morbidity
4.1. Neonatal intensive care unit admission
4.2. Intraventricular haemorrhage (IVH) grade II or above - defined as bleeding into the ventricles
4.2.1. Grade II (moderate) – IVH occupies <50% of the lateral ventricle volume
4.2.2. Grade III (severe) – IVH occupies >50% of the lateral ventricle volume
4.2.3. Grade IV (severe) – haemorrhagic infarction in periventricular white matter ipsilateral to a large IVH
4.3. Ventilation - defined as need of positive pressure (continuous positive airway pressure [CPAP] or nasal continuous positive airway pressure [NCPAP]) or intubation
4.4. Neonatal sepsis - confirmed bacteraemia in cultures
4.5. Anaemia – defined as low haemoglobin and/or haematocrit requiring blood transfusion
4.6. Respiratory distress syndrome - defined as need of surfactant and ventilation as a result of prematurity
4.7. Necrotising enterocolitis (NEC) requiring surgical intervention. NEC is defined by a combination of clinical, radiological and laboratory features:
4.7.1. Systemic signs - apnoea, bradycardia, temperature instability, hypotension
4.7.2. Intestinal signs - abdominal distension, gastric residuals, bloody stools, absent bowel sounds, abdominal tenderness, peritonitis
4.7.3. Radiological signs - pneumatosis intestinalis or portal venous air, pneumoperitoneum
4.7.4. Laboratory changes - metabolic and or respiratory acidosis, thrombocytopaenia, DIC
4.8. Composite of any of the above
5. To determine the effect of low-dose aspirin on the incidence of neonatal birthweight below the 3rd, 5th and 10th centile
5.1. Birthweight will be recorded in the participants’ medical notes and birthweight percentile for gestational age at delivery is calculated using a normal range derived from our population
6. To determine the effect of low-dose aspirin on the incidence of stillbirth or neonatal death
6.1. Due to any cause
6.2. Ascribed to PE or fetal growth restriction (FGR)
6.3. In association with maternal or neonatal bleeding
7. To determine the effect of low-dose aspirin on the incidence of spontaneous preterm delivery at <34 weeks and <37 weeks
7.1. Spontaneous delivery at <34 weeks (early preterm) and at <37 weeks (total preterm) includes those with spontaneous onset of labour and those with preterm pre-labour rupture of membranes

Secondary outcome measures from 12/03/2013 to 21/04/2016:
1. Development of early onset pre-eclampsia requiring delivery before 34 weeks' gestation and pre-eclampsia at any gestation
2. Birthweight below the 3rd, 5th and 10th centile
3. Stillbirth or neonatal death due to any cause
4. Stillbirth or neonatal death ascribed to pre-eclampsia or fetal growth restriction
5. Stillbirth or neonatal death in association with maternal or neonatal bleeding
6. Rate of neonatal intensive care unit admission
7. Composite measure of neonatal mortality and morbidity
8. Placental abruption (clinically or on placental examination)
9. Spontaneous preterm delivery <34 weeks and <37 weeks
Measures will be obtained at the end of the pregnancy.

Previous secondary outcome measures until 12/03/2013:
1. Development of pre-eclampsia according to gestation at delivery: early (less than 34 weeks), intermediate (34 - 37 weeks) and late-PE (greater than 37 weeks)
2. Birthweigth below the 3rd, 5th and 10th centile
3. Stillbirth or neonatal death due to any cause
4. Stillbirth or neonatal death ascribed to pre-eclampsia or IUGR
5. Stillbirth or neonatal death ascribed to maternal or neonatal bleeding
6. Rate of neonatal intensive care unit admission
7. Placental abruption (clinically or on placental examination)
Measures will be obtained at the end of the pregnancy.

Overall trial start date

02/01/2014

Overall trial end date

30/11/2016

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 12/03/2013:
1. Aged 18 years or over
2. Singleton pregnancies
3. Live fetus at 11-13 weeks of gestation
4. High-risk for preterm pre-eclampsia will be defined at 11-13 weeks by the algorithm combining maternal history and characteristics, biophysical findings (mean arterial pressure and uterine artery Dopplers) and biochemical factors (pregnancy associated plasma protein-A [PAPP-A] and placental growth factor [PlGF]).

Previous inclusion criteria until 12/03/2013:
All singleton pregnancies with a live foetus at 11+0 - 13+6 weeks of gestation.

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

1760

Participant exclusion criteria

Current exclusion criteria as of 28/04/2014:
1. Multiple pregnancies
2. Pregnancies complicated by major fetal abnormality identified at the 11-13 weeks assessment
3. Women who are unconscious or severely ill, those with learning difficulties, and serious mental illness
4. Bleeding disorders such as Von Willebrand’s disease
5. Peptic ulceration
6. Hypersensitivity to aspirin or already on long term non-steroidal anti-inflammatory medication
7. Age < 18 years
8. Women taking low-dose aspirin regularly
9. Concurrent participation in another drug trial or at any time within the previous 28 days
10. Any other reason the clinical investigators think will prevent the potential participant from complying with the trial protocol

Exclusion criteria from 12/03/2013 to 28/04/2014:
1. Multiple pregnancies
2. Pregnancies complicated by major fetal abnormality identified at the 11-13 weeks assessment
3. Women who are unconscious or severely ill, those with learning difficulties, and serious mental illness
4. Bleeding disorders such as Von Willebrand’s disease
5. Peptic ulceration
6. Hypersensitivity to aspirin or already on long term non-steroidal anti-inflammatory medication
7. Age < 18 years

Original exclusion criteria until 12/03/2013:
1. Major foetal abnormalities identified at the 11+0 - 13+6 weeks assessment
2. Women who are unconscious or severely ill
3. Learning difficulties
4. Serious mental illness
5. Women with bleeding disorders
6. Peptic ulceration
7. Hypersensitivity to aspirin
8. Under the age of 18 years

Recruitment start date

23/04/2014

Recruitment end date

14/04/2016

Locations

Countries of recruitment

Belgium, Greece, Israel, Italy, Spain, United Kingdom

Trial participating centre

King's College Hospital
London
SE5 9RS
United Kingdom

Trial participating centre

Hospital Universitario Virgen de la Arrixaca
Murcia
-
Spain

Trial participating centre

North Middlesex University Hospital
London
-
United Kingdom

Trial participating centre

University Hospital Lewisham
London
-
United Kingdom

Trial participating centre

Medway Maritime Hospital
Gillingham
-
United Kingdom

Trial participating centre

Southend University Hospital
Westcliff-on-Sea
-
United Kingdom

Trial participating centre

Homerton University Hospital
London
-
United Kingdom

Trial participating centre

CHU Brugmann
Brussels
-
Belgium

Trial participating centre

Hospiten Sur
Tenerife
-
Spain

Trial participating centre

Attikon University Hospital
Athens
-
Greece

Trial participating centre

Hospital Universitario San Cecilio
Granada
-
Spain

Trial participating centre

Ospedale Maggiore Policlinico
Milan
-
Italy

Trial participating centre

Rabin Medical Center
Petah Tikva
-
Israel

Sponsor information

Organisation

University College London (UK)

Sponsor details

c/o Susan Tebbs
Gower Street
London
WC1E 6BT
United Kingdom

Sponsor type

Government

Website

http://www.ucl.ac.uk/cctu

Funders

Funder type

Research council

Funder name

Seventh Framework Programme

Alternative name(s)

EC Seventh Framework Programme, European Commission Seventh Framework Programme, EU Seventh Framework Programme, European Union Seventh Framework Programme, FP7

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Belgium

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2016 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/27354081

Publication citations

Additional files

Editorial Notes

01/07/2016: Publication reference added. 21/04/2016: the following changes were made to the trial record: 1. The plain English summary was added. 2. Phase was changed from IV to III. 3. The overall trial end date was changed from 02/01/2016 to 30/11/2016. 4. The target number of participants was changed from 1684 to 1760. 5. Greece and Israel were added to the countries of recruitment. 28/04/2014: the following changes were made to the trial record: 1. The target number of participants was changed from 1560 to 1684. 2. Belgium, Italy and Spain were added to the countries of recruitment. 3. The sponsor was changed from King's College Hospital NHS Foundation Trust to University College London. 12/03/2013: the following changes were made to the trial record: 1. The scientific title was previously "Randomised controlled trial using low dose aspirin in women at high-risk of pre-eclampsia at 11+0 - 13+6 weeks". 2. The overall trial start date was changed from 01/02/2011 to 02/01/2014. 3. The overall trial end date was changed from 01/02/2016 to 02/01/2016. 4. The target number of participants was changed from 2294 to 1560.