DORA
Research type
Research Study
Full title
A randomised crossover design study comparing the pharmacokinetics and pharmacodynamics of two single oral doses of aspirin (75 mg v150mg) in pregnant women at risk of pre-eclampsia.
IRAS ID
253665
Contact name
Stephen Robson
Contact email
Sponsor organisation
Newcastle upon Tyne Hospitals Foundation Trust
Eudract number
2021-000071-36
ISRCTN Number
14693054
Duration of Study in the UK
0 years, 6 months, 1 days
Research summary
Research Summary
Annually over 3 million babies die before or soon after birth. This devastating outcome can be explained by problems with the placenta (afterbirth), the organ that supplies nutrients and oxygen to the baby. A poorly functioning placenta can cause slow growth of the baby and blood pressure problems in mother; this can lead to the death of a mother or/and a baby. This study will focus on priorities identified by the James Lind Alliance Priority Setting Partnership (JLA PSP); hypertension (high blood pressure) in pregnancy in 2018 and stillbirth in 2015.
Research has shown that pregnant women with certain medical problems who take a low dose of aspirin are less likely to have pregnancy complications. It is uncertain how much aspirin is needed; this is partly because aspirin does not work in the same way in all women. Women who do not respond to aspirin treatment are more likely to develop pregnancy complications. It is possible that increasing the dose of aspirin (from 75 mg to 150 mg a day) may be a simple and safe way to increase the number of women who respond to aspirin and thereby reduce the number of pregnancy complications.
Proposed study will consist of two visits 7 days apart when women will be asked to take 75 or 150 mg of aspirin in random order (chosen by a chance) and to provide blood samples over a 24-hour period. All participants will stay in hospital for the first 4 hours after taking the aspirin but then will be able to go home overnight to return the following day to complete the collection. Participants will be offered a 4D ultrasound scan later in pregnancy to thank them for the participation.
The study results will enable us to understand how quickly aspirin is removed from the body during pregnancy and how aspirin affects the function of blood components over 24-hour period in high risk women. In future this will help inform doctors and researchers to understand use of aspirin in pregnancy better and to design intervention to improve pregnancy outcomes.Summary of Results
A single dose of 150 mg of aspirin produced higher plasma exposure of SA in comparison to 75 mg (median SA AUC0-19 16.7 µg *h/ml vs 6.8 µg *h/ml). Plasma SA concentrations were significantly above baseline values at all-time points, but there was some overlap between the maximum recorded SA concentrations at baseline and that found after 15 h. Pharmacokinetic models suggest that plasma SA concentrations could be above the maximum concentration recorded at baseline for the first 11 hours after 75 mg and for 12 hours after 150 mg aspirin dosing, providing a time frame to confirm recent aspirin ingestion. Aspirin taken at 150 mg produced a greater reduction in serum TbxB2 (median TbxB2 AUC0-19 102.92 ng *h/ml under 75 mg aspirin dose vs 18.9 ng *h/ml under 150 mg dose). Participant characteristics are shown in Table 1. No adverse events were reported during the trial.
REC name
Wales REC 1
REC reference
21/WA/0066
Date of REC Opinion
15 Apr 2021
REC opinion
Further Information Favourable Opinion