Use of aspirin for the prevention of preeclampsia in twin pregnancies
| ISRCTN | ISRCTN86684235 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN86684235 |
| EudraCT/CTIS number | 2019-003341-15 |
| IRAS number | 269958 |
| Secondary identifying numbers | CPMS 50869, IRAS 269958 |
- Submission date
- 05/08/2022
- Registration date
- 22/08/2022
- Last edited
- 19/11/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
Background and study aims
Preeclampsia (PE) is a medical condition that can happen during pregnancy after 20 weeks and it is characterised by high blood pressure and the presence of protein in the urine or in its absence the finding of maternal organ dysfunction. PE is one of the leading causes of maternal and perinatal death and disabilities. There is extensive evidence that in singleton high-risk pregnancies for PE, the use of aspirin (150 mg/day from 12 until 36 weeks of gestation) reduces the chances of developing PE before 32 weeks by 89% and PE before 37 weeks by 62%. The rate of PE in twin pregnancies is about 9%, which is 3–times higher than in singleton pregnancies. Few studies investigated the use of aspirin in reducing the risk of PE in twin pregnancies, but the results are inconsistent with the findings in singleton pregnancies. Therefore, the aim of this study is to determine whether taking low-dose aspirin can reduce the risk of PE in twin pregnancies.
Who can participate?
Anyone pregnant with twins, aged over 18 years old and had a first-trimester scan between 11+2 - 13+6 weeks of pregnancy
What does the study involve?
Participants will be randomised and will take 2 tablets per day, either Aspirin or placebo, from 14+3 weeks until 36 weeks of pregnancy or delivery. There will be 3 telephone calls and 4 follow-up visits that will happen at the same time as the regular scan appointments.
What are the possible benefits and risks of participating?
The possible benefits of participating include a reduction in the chances of developing preeclampsia, which can have a positive impact on the health of both the mothers and their children. The possible risks include potential pain from the blood collection at 3 of the clinical visits (optional). From taking the tablets, there are additional risks of developing: allergic reactions, stomach ache, nausea and gastric bleeding, and increased vaginal bleeding before and after delivery. Based on currently available evidence, no major risks are anticipated.
Where is the study run from?
Fetal Medicine Foundation (UK)
When is the study starting and how long is it expected to run for?
August 2019 to October 2028
Who is funding the study?
Fetal Medicine Foundation (UK)
Who is the main contact?
Prof. Kypros Nicolaides
kypros@fetalmedicine.com
Contact information
Scientific
Harris Birthright Research Centre for Fetal Medicine
King’s College Hospital
London
SE5 8BB
United Kingdom
| Phone | +44 (0)20 3299 8256 |
|---|---|
| kypros@fetalmedicine.com |
Scientific
Fetal Medicine Unit
Hospital Universitario Virgen de la Arrixaca
Ctra. Madrid-Cartagena
Murcia
30120
Spain
| Phone | +34 (0)676 67 26 17 |
|---|---|
| catalina.de1@um.es |
Scientific
Harris Birthright Research Centre for Fetal Medicine
King’s College Hospital
London
SE5 8BB
United Kingdom
| Phone | +44 (0)20 3299 7164 |
|---|---|
| argyro.syngelaki@nhs.net |
Scientific
Fetal Medicine Research Institute
16-20 Windsor Walk
London
SE5 8BB
United Kingdom
| Phone | +44 (0)7857306268 |
|---|---|
| angel.leung2@nhs.net |
Study information
| Study design | Randomized case-controlled study |
|---|---|
| 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 below to request a patient information sheet |
| Scientific title | Aspirin versus placebo in twin pregnancies for preeclampsia prevention: a multicenter, randomised, double-blind, placebo-controlled trial (ASPRE-T) |
| Study acronym | ASPRE-T |
| Study objectives | To evaluate the effectiveness of low-dose aspirin in reducing the risk of preterm preeclampsia in twin pregnancy, the study will compare the results of the interventional group with the results of the placebo group |
| Ethics approval(s) | Approved 12/04/2022, London - Surrey Borders Research Ethics Committee (The Old Chapel, Royal Standard Place, HRA, Nottingham, NG1 6FS, UK; +44 (0)20 7104 8057; surreyborders.rec@hra.nhs.uk), ref: 21/LO/0757 |
| Health condition(s) or problem(s) studied | Preterm preeclampsia in twin pregnancy |
| Intervention | Women will be recruited from their routine first-trimester scan where the eligibility criteria will be assessed. Women who accept to take part in the trial and sign the consent form will agree to have some of their blood stored for future analysis. They routinely will have bloods taken for screening of trisomies and at the same time will be consented for bloods for the research study. Routinely in the units involved, they will also have basic clinical investigations of blood pressure, height, weight and a medical history taken. Upon participation, they will then be randomised to placebo or aspirin and asked to take this until 36 weeks of gestation. From this point on, women will continue on their normal follow-up pathway for twin pregnancies. Those with monochorionic pregnancies will actually be seen more often for clinical needs, but in terms of research follow-up, in addition to their routine scans, and clinical investigations at the 20-, 28-, 31- and 35-week time points, we will determine compliance of medication by counting their remaining tablets and assessing their diary cards for adverse events. The only additional blood sampling we will be asking for will be at the 20- and 32-week visits. They will receive telephone interviews at 15 and 24 weeks of gestation, followed by a call 4 weeks after the last dose of the investigational medicinal product (IMP). The purpose of these will be reminders to take the medication, but more importantly to assess for adverse events. |
| Intervention type | Other |
| Primary outcome measure | Incidence of preeclampsia (PE) requiring delivery before 37 weeks gestation in twin pregnancies, measured by examination of hospital records and patient interviews. PE will be defined by the American College of Obstetricians and Gynecologists (ACOG 2013). |
| Secondary outcome measures | All measured by examination of hospital records and patient interviews 1. Incidence of PE requiring delivery before 32 weeks, 34 weeks, 37 weeks and at any gestation, 2. For all features of severe PE the timepoint is from diagnosis of PE until maternal discharge from hospital- Features of severe PE include: 2.1. Stroke 2.2. Eclampsia 2.3. Systolic blood pressure >160 mmHg on at least one occasion 2.4. Systolic blood pressure >160 mmHg on at least one occasion 2.5. Respiratory failure 2.6. Myocardial ischemia or infarction 2.7. Pulmonary edema 2.8. Hepatic dysfunction 2.9. Hepatic hematoma or rapture 2.10. Platelet count <100 x 109/litre 2.11. Abnormal liver function enzymes (ALT or AST >67 iu/litre), 2.12. Acute kidney injury 2.13. Creatinine >150 μmol/L 2.14. Cortical blindness 2.15. Retinal detachment 2.16. Transfusion of any blood products, 2.17. HELLP syndrome, 2.18. Placental abruption 2.19. Postpartum hemorrhage 2.20. Intensive therapy or high-dependency unit admission; 2.21. Confirmed sepsis 2.22. Total number of nights in hospital 3. Gestational hypertension (GH) requiring delivery before 37 weeks’ gestation defined by ACOG 2013 4. Birth before 32, 34 and 37 weeks, either: 4.1. Spontaneous 4.2. Iatrogenic for PE, GH or Fetal Growth Restriction (FGR) 4.3. Iatrogenic for other reasons 5. Death of one twin and/or both twins at timepoint before discharge from hospital 5.1. Miscarriage of the whole pregnancy or death of one twin before 24 weeks’ gestation 5.2. Stillbirth or neonatal death of one or both twins at 32 weeks, 34 weeks, 37 weeks and at any gestation 6. Birthweight <3rd, <5th and <10th percentile for gestational age measured by Fetal Medicine Foundation birthweight chart (Nicolaides et al., 2018) 7. Placental abruption timepoint at 32 weeks, 34 weeks, 37 weeks and at any gestation 8. Postpartum hemorrhage timepoint first 24 hours after delivery 9. Neonatal morbidity including any of the following measured by examination of hospital records and patients’ interviews, timepoint until discharge from hospital after birth: 9.1. Intraventricular hemorrhage (IVH) grade II or above 9.2. Neonatal sepsis 9.3. Encephalopathy 9.4. Neonatal seizures 9.5. Anaemia 9.6. Respiratory distress syndrome 9.7. Necrotizing enterocolitis 9.8. Composite of any of the above 10. Neonatal therapy including any of the following measured by examination of hospital records and patients’ interviews, timepoint until discharge from hospital after birth: 10.1. Neonatal intensive care unit admission 10.2. Ventilation 10.3. Composite of any of the above 10.4. Length of stay in neonatal intensive care unit |
| Overall study start date | 08/08/2019 |
| Completion date | 31/10/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 2400; UK Sample Size: 1200 |
| Key inclusion criteria | 1. Aged 18 years old and over 2. DCDA or MCDA twin pregnancies 3. Both live fetuses at 11+2-13+6 weeks of gestation 4. Informed and written consent |
| Key exclusion criteria | 1. Monoamniotic twins 2. Triplet pregnancies that had undergone embryo reduction to twins or with one vanishing twin 3. Pregnancies complicated by a major fetal abnormality or nuchal translucency thickness > 3.5 mm identified at the 11+2-13+6 weeks scan 4. MCDA twin pregnancies in which there are early signs of TTTS or sFGR defined by a 20% discordance in CRL at the 11+2-13+6 weeks’ scan 5. Those who lack capacity and who are unable to provide informed consent to take part 6. Women taking low-dose aspirin regularly (administration must have ceased > 7 days prior to randomization) 7. Participation in another drug trial within the previous 7 days 8. Haemorrhagic diathesis; coagulation disorders such as haemophilia and thrombocytopenia or concurrent anticoagulant therapy 9. Active or history of recurrent peptic ulceration and/or gastric/intestinal haemorrhage, or other kinds of bleeding such as cerebrovascular haemorrhages 10. Patients who are suffering from known gout, severe hepatic impairment or severe renal impairment 11. Hypersensitivity to salicylic acid compounds or prostaglandin synthetase inhibitors (e.g. certain asthma patients who may suffer an attack or faint and certain patients who may suffer from bronchospasm, rhinitis and urticaria) or to any excipients (see section 6.1 of the SmPC for details) 12. Patients on long-term non-steroidal anti-inflammatory medication 13. Not fluent in local language and absence of an interpreter 14. Any other reason the clinical investigators think will prevent the potential participant from complying with the trial protocol |
| Date of first enrolment | 30/08/2022 |
| Date of final enrolment | 30/09/2028 |
Locations
Countries of recruitment
- Austria
- Belgium
- Bulgaria
- Denmark
- England
- Germany
- Greece
- Hungary
- Ireland
- Israel
- Italy
- Poland
- Portugal
- Spain
- United Kingdom
Study participating centres
Sterling Way
London
N18 1QX
United Kingdom
Westcliff-On-Sea
Essex
SS0 0RY
United Kingdom
London
SE5 9RS
United Kingdom
Gillingham
ME7 5NY
United Kingdom
London
E9 6SR
United Kingdom
London
SE1 7EH
United Kingdom
London
SE13 6LH
United Kingdom
Kingston upon Thames
KT2 7QB
United Kingdom
369 Fulham Road
London
SW10 9NH
United Kingdom
Bordesley Green
Birmingham
B9 5SS
United Kingdom
Ctra. Madrid-Cartagena, s/n
Murcia
-
Spain
Plaza de Cruces, s/n
Bizkaia
-
Spain
Avenida Constitución, 100
Granada
-
Spain
Spitalgasse 23
Vienna
1090
Austria
Sofia
1330
Bulgaria
Blegdamsvej 9
Copenhagen
DK – 2100
Denmark
Fetscherstraße 74
Dresden
-
Germany
Athens
115 28
Greece
27 Baross street
Budapest
-
Hungary
Saint James'
Dublin
D08 XW7X
Ireland
Milan
20122
Italy
Starynkiewicza 1
Warsaw
02-015
Poland
Leuven
3000
Belgium
Stadium Rd
London
SE18 4QH
United Kingdom
Broomfield
Chelmsford
CM1 7ET
United Kingdom
Basildon
SS16 5NL
United Kingdom
-
Bulgaria
Prague
-
Czech Republic
Milan
20132
Italy
-
Italy
Warsaw
01-211
Poland
-
Poland
Portugal
-
Spain
Rom Valley Way
Romford
RM7 0AG
United Kingdom
-
Israel
Torrejón de Ardoz
Madrid
28850
Spain
Sponsor information
Research organisation
C/ Campo, 12
Teaching Pavilion of the Virgen de la Arrixaca University Clinical Hospital
3rd Floor
El Palmar
Murcia
30120
Spain
| Phone | +34 (0)968359763 |
|---|---|
| lola.serna@carm.es | |
| Website | https://www.ffis.es/ |
"ROR" |
https://ror.org/05m5has32 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- FMF
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/10/2029 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. Planned publication in a high-impact peer-reviewed journal. The study protocol will be published on the Fetal Medicine Foundation website (https://www.fetalmedicine.org). Publication of study results is anticipated within one year from the study end and analysis. 2. Presentation at international conferences 3. Internal report 4. Website |
| IPD sharing plan | The 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? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
19/11/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 30/08/2025 to 31/09/2028.
2. The overall study end date was changed from 01/09/2025 to 31/10/2028.
3. The intention to publish date was changed from 30/09/2026 to 31/10/2029.
21/11/2023: The recruitment end date was changed from 30/08/2024 to 30/08/2025.
25/05/2022: Contact details updated.
05/08/2022: Trial's existence confirmed by the NIHR.
