First Trimester Aspirin Trial
| ISRCTN | ISRCTN13633058 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13633058 |
| EudraCT/CTIS number | 2013-003778-29 |
| Secondary identifying numbers | 62340803 |
- Submission date
- 28/10/2010
- Registration date
- 12/01/2011
- Last edited
- 24/08/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
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?
It is not known if there is a direct benefit to a participant’s current pregnancy. The participant is in greater regular contact with the clinical team during pregnancy than is routine and the information gained from the study may help the participant and/or other women in the future who are at high risk from developing preeclampsia. The use of low-dose aspirin appears to be safe in pregnancy.
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
Contact information
Scientific
King's College Hospital
Harris Birthright Research Centre
Second Floor
Fetal Medicine Research Institute
16-20 Windsor Walk
London
SE5 8BB
United Kingdom
Study information
| Study design | Double-blind randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Combined multi-marker screening and randomised patient treatment with ASpirin for evidence-based PRE-eclampsia prevention |
| Study 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(s) | NRES Committee London - Fulham, 12/11/2013, ref: 13/LO/1479 |
| Condition | Pre-eclampsia |
| Intervention | Current interventions as of 16/04/2014: 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 12/03/2013 to 15/04/2014: 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Aspirin |
| Primary outcome measure | 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 study start date | 02/01/2014 |
| Overall study end date | 03/11/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | 1760 |
| 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 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 Willebrands 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 Willebrands 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
- England
- Greece
- Israel
- Italy
- Spain
- United Kingdom
Study participating centres
SE5 9RS
United Kingdom
-
Spain
-
United Kingdom
-
United Kingdom
-
United Kingdom
-
United Kingdom
-
United Kingdom
-
Belgium
-
Spain
-
Greece
-
Spain
-
Italy
-
Israel
Sponsor information
Government
c/o Susan Tebbs
Gower Street
London
WC1E 6BT
United Kingdom
| Website | http://www.ucl.ac.uk/cctu |
|---|---|
"ROR" |
https://ror.org/02jx3x895 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- EC Seventh Framework Programme, European Commission Seventh Framework Programme, EU Seventh Framework Programme, European Union Seventh Framework Programme, FP7
Results and Publications
| Intention to publish date | 03/11/2017 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal during 2017. |
| IPD sharing plan | The current data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 28/06/2016 | Yes | No | |
| Results article | results | 17/08/2017 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
24/08/2017: Publication reference added.
10/02/2017: The overall trial end date was changed from 30/11/2016 to 03/11/2016.
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.
