What happens to low doses of aspirin (75 and 150 mg) and how it affects certain blood particles in pregnant women at risk of pre-eclampsia?
| ISRCTN | ISRCTN14693054 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14693054 |
| EudraCT/CTIS number | 2021-000071-36 |
| IRAS number | 253665 |
| Secondary identifying numbers | IRAS 253665 |
- Submission date
- 12/01/2021
- Registration date
- 09/03/2021
- Last edited
- 24/10/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
Background and study aims
Problems with the proper functioning of the heart and blood vessels, also known as cardiovascular disease (CVD), are one of the main causes of death in the North East of England. In addition to the widely known risk factors, pregnancy-related problems affecting blood pressure predispose many young women and their children to CVD later in life. It is important to prevent women from developing high blood pressure conditions such as pre-eclampsia during pregnancy in order to improve the health-related outcomes for both them and their babies.
Use of low-dose aspirin (75 mg -150 mg) is recommended to prevent blood pressure complications in pregnancy. The effects of aspirin on blood (and specifically platelets – the cells that help blood clot), and the way aspirin is broken down and removed from the body, have been studied in non-pregnant people. However, surprisingly, no such studies have been performed in pregnant women, even though both measures are expected to change greatly in this population.
This study will measure the disappearance of the aspirin from the body and its effects on blood clotting function in pregnant women, for two different doses of aspirin. Knowing the effects of aspirin in pregnant women will help doctors to optimise the dose of aspirin given to pregnant women and support a more personalised use of aspirin for effective CVD prevention in this population.
Who can participate?
Pregnant women at risk of pre-eclampsia
What does the study involve?
Pregnant women, who have been prescribed aspirin, because of their increased risk of developing high blood pressure in pregnancy, will be asked to take two aspirin doses in a random order (chosen by chance) and to donate blood samples at regular intervals to measure the disappearance of the drug from the body and the drug’s effects on blood clotting function in pregnant women.
What are the possible benefits and risks of participating?
There will be no direct benefit to participants from this trial. However, the study team recognise that participation in this trial is time-consuming, therefore all effort will be made to ensure participant comfort during their research visit. This includes a comfortable space to rest and the provision of standardised meals. To show gratitude to women who complete the study schedule in full, a complimentary 28 weeks 4D scan will be offered.
All women will be prescribed aspirin for clinical reasons. Monitoring of adverse effects will be performed in person during the first 4 hours following aspirin ingestion and again at 24 hours. All women will be given emergency contact numbers to ensure access to medical care in case needed outside of their research visits.
Where is the study run from?
Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
March 2019 to March 2022
Who is funding the study?
Newcastle Upon Tyne Hospitals NHS Charity (UK)
Who is the main contact?
Mrs Raya Vinogradov
raya.vinogradov@ncl.ac.uk
Contact information
Public
The Reproductive Research Team
Level 6
Leazes Wing
The Royal Victoria Infirmary
Queen Victoria Road
Newcastle
NE1 4LP
United Kingdom
 ORCID ID |
0000-0001-9375-7915 |
|---|---|
| Phone | +44 (0)191 2820540 |
| raya.vinogradov@ncl.ac.uk |
Scientific
School of Population & Health Sciences
Reproductive and Vascular Biology Group
3rd Floor, William Leech Building
The Medical School
Newcastle University
Newcastle
NE2 4HH
United Kingdom
| Phone | +44 (0)191 282 4132 |
|---|---|
| s.c.robson@ncl.ac.uk |
Study information
| Study design | Randomized crossover study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format. Please use contact details to request a participant information sheet |
| Scientific title | A randomised crossover design study comparing the pharmacokinetics and pharmacodynamics of two single Doses of ORal Aspirin (75 mg v 150 mg) in pregnant women at risk of pre-eclampsia (DORA) |
| Study acronym | DORA |
| Study objectives | To compare aspirin pharmacokinetics (plasma salicylic acid concentrations) and pharmacodynamics (serum thromboxane B2 concentrations) in pregnant women at 11-16 weeks gestation’ following the administration of a single oral dose of either 75 mg or 150 mg aspirin. |
| Ethics approval(s) | Approved 30/03/2021, Wales REC 1 (Health and Care Research Wales Support and Delivery Centre, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, UK; +44 (0)2920 230457; Wales.REC1@wales.nhs.uk), ref: 21/WA/0066 |
| Health condition(s) or problem(s) studied | Pre-eclampsia |
| Intervention | Online non-blinded envelope randomisation will be performed. The lab will be blinded to the randomisation. Participants will be randomised to either a sequence of a single dose of 75 mg aspirin followed by a 7-day washout period and then a single dose of 150 mg aspirin, or a single dose of 150 mg aspirin followed by a 7-day washout period and then a single dose of 75 mg aspirin. Blood sampling will be performed to assess levels of salicylic acid and thromboxane B2. Participants will be asked to abstain from taking aspirin for 7 days between the doses. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Acetylsalicylic acid |
| Primary outcome measure | 1. Pharmacokinetics and pharmacodynamics measured using serum salicylic acid concentration and serum thromboxane B2 concentration from blood samples taken at baseline, 1, and 8 days |
| Secondary outcome measures | 1. Time to the detection limit of salicylic acid in plasma measured from blood samples taken at baseline, 1, and 8 days |
| Overall study start date | 01/03/2019 |
| Completion date | 31/03/2022 |
Eligibility
| Participant type(s) | Other |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target number of participants | 14 |
| Total final enrolment | 16 |
| Key inclusion criteria | 1. Pregnant women at risk of pre-eclampsia according to NICE criteria |
| Key exclusion criteria | 1. Hypersensitivity to aspirin, salicylic acid compounds, or prostaglandin synthase inhibitors (e.g. certain asthma patients who may suffer an attack or faint) 2. Active, or history of, recurrent peptic ulcer and/or gastric/intestinal haemorrhage, or other kinds of bleeding such as cerebrovascular haemorrhage 3. Haemorrhagic diathesis or coagulation disorders such as hemophilia and thrombocytopenia 4. Severe hepatic or renal impairment 5. Gout 6. Taken aspirin over the preceding 4 weeks 7. Current anticoagulant therapy 8. Unable to give informed consent 9. Multiple pregnancy 10. Known fetal anomaly 11. Vegetarian/vegan diet |
| Date of first enrolment | 01/07/2021 |
| Date of final enrolment | 31/03/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Level 6 Leazes Wing
Royal Victoria Infirmary
Queen Victoria Road
Newcastle
NE1 4LP
United Kingdom
Sponsor information
Hospital/treatment centre
Freeman Hospital
Freeman Road
Newcastle upon Tyne
Newcastle
NE7 7DN
England
United Kingdom
| Phone | +44 (0) 191 2825959 |
|---|---|
| tnu-tr.sponsormanagement@nhs.net | |
| Website | http://www.newcastle-hospitals.org.uk/ |
"ROR" |
https://ror.org/05p40t847 |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | 31/01/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | A lay summary will be available on project web pages. Full results will be published in professional journals. The study protocol is not available in web format, please contact R Vinogradov at raya.vinogradov@ncl.ac.uk for further information. |
| IPD sharing plan | The datasets (anonymised) generated and analysed during the current study will be available upon request from S Robson (s.c.robson@newcastle.ac.uk)/ R Vinogradov (raya.vinogradov@ncl.ac.uk) subject to ethical approvals. We reserve our right to review sharing policy depending on a nature of the request. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.9 | 08/03/2021 | 11/08/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Basic results | 07/07/2023 | 07/07/2023 | No | No | |
| Results article | 21/10/2024 | 24/10/2024 | Yes | No |
Additional files
Editorial Notes
24/10/2024: Publication reference added.
07/07/2023: Basic results uploaded. The intention to publish date was changed from 01/10/2022 to 31/01/2024.
17/08/2022: Total final enrolment added.
11/08/2022: Protocol file uploaded.
11/01/2022: The following changes were made to the trial record:
1. The overall end date was changed from 31/01/2022 to 31/03/2022.
2. The recruitment end date was changed from 31/01/2022 to 31/03/2022.
3. The plain English summary was updated to reflect these changes.
08/12/2021: The overall trial end date has been changed from 01/12/2021 to 31/01/2022 and the plain English summary has been updated accordingly.
12/10/2021: The recruitment end date was changed from 01/10/2021 to 31/01/2022.
10/05/2021: The recruitment start date was changed from 01/05/2021 to 01/07/2021.
13/04/2021: The following changes were made to the trial record:
1. The ethics approval was added.
2. The recruitment start date was changed from 01/04/2021 to 01/05/2021.
14/01/2021: Trial’s existence confirmed by Newcastle upon Tyne Hospitals NHS Charity.
