The PIONEER Study - A study to investigate whether taking the medication Pravastatin reduces the number of babies born too early (preterm, i.e., before 37 weeks of pregnancy) and, if so, how it works in the body to do this.

Plain English summary of protocol

Background and study aims
Around 7 out of every 100 UK babies are born too early (preterm, i.e., before 37 weeks of pregnancy). Being born preterm is the most common cause of babies dying before the age of one year in the UK; 1 in 3 of those who survive are diagnosed with cerebral palsy. This study will test whether the medicine Pravastatin reduces the number of babies born preterm. It is not fully understood why some babies are born early, and there are few effective treatments to prevent this from happening. Research shows it is likely that early labour may occur because of types of inflammation in the mother’s body. Taking a medication which reduces inflammation, such as Pravastatin, could therefore reduce the number of babies being born preterm. Pravastatin has been tested for the treatment and prevention of other pregnancy problems, with no safety concerns for women or their babies, and some studies suggest that it may reduce the number of babies born preterm. This study will test whether taking one tablet of Pravastatin once a day, from between 16-20 weeks of pregnancy until 37 weeks, reduces the number of babies born too early.

Who can participate?
Young and adult women aged 16 years old and over who attend Preterm Birth Prevention clinics

What does the study involve?
Participants will be asked if they would like to join the study. If they join, half will be given Pravastatin and half will be given a placebo (a dummy tablet which looks like Pravastatin but does not contain Pravastatin). Neither the women nor the researchers will know which tablets they are taking until the end of the study. The study will record how many weeks of pregnancy their babies are born and compare this between the two groups of women. The study will also measure levels of certain bacteria and markers of inflammation, which may be related to babies being born early, by collecting blood, fluid produced in the vagina and stool samples. Any complications the women or their babies have will be recorded and the babies’ development will be assessed at two years of age.

What are the possible benefits and risks of participating?
There is a possibility that participants who receive Pravastatin will have a lower chance of preterm birth, but we cannot be certain. This is what this study will help us to find out. If Pravastatin does have this effect, the research could help us to improve the options for pregnant women who are at risk of preterm birth in the future. Participants may also benefit from the increased contact that comes with being a part of a clinical study.

The potential risks and burdens for the trial are summarised in the Participant Information Sheet (PIS), which has been reviewed and approved by our public contributors.
• Possible side effects from the trial medication. These are explained in the PIS, including how likely they are to occur, with clarity that side effects relate to the participant and not their baby.
• Discomfort or pain when having a blood sample taken. Localised bruising and discomfort can occur at the site of venipuncture. Infrequently fainting may occur. Blood samples must be taken from all participants to confirm eligibility and at 28 weeks to assess liver transaminase levels (ALT or AST) - additional blood samples will be taken from all participants at sites taking part in the mechanistic sub-study. Samples will be taken by trained phlebotomists and every effort will be made to reduce pain or discomfort.
• Mild discomfort when having a vaginal swab taken (only participants in the mechanistic sub-study). This will be done by trained clinical staff who are experienced in taking these swabs and will be conducted in such a manner as to maintain privacy and dignity.
• Loss of participant's time to attend research visits at the hospital, take part in qualitative interviews or complete follow-up at home. Trial activities will be integrated into usual care visits where possible to reduce the burden of participation, and researchers will make efforts to arrange visits/calls for convenient times. Participants will also be reimbursed for some expenses.

Where is the study run from?
University Hospitals Bristol and Weston NHS Foundation Trust

When is the study starting and how long is it expected to run for?
February 2024 to February 2028

Who is funding the study?
National Institute for Health and Care Research (NIHR)

Who is the main contact?
pioneer-trial@bristol.ac.uk

Contact information

Dr Katherine Birchenall
Scientific, Principal investigator

Women and Children's Health, University Hospitals Bristol and Weston NHS Foundation Trust
Bristol
BS8 1NU
United Kingdom

ORCID ID	0000-0002-7261-4832
Phone	None provided
Email	katherine.birchenall@bristol.ac.uk

Dr Taemi Kawahara
Public

PIONEER Central Trial Office, Bristol Trials Centre, Bristol Medical School, University of Bristol, 1-5 Whiteladies Road
Bristol
BS8 1NU
United Kingdom

Phone	+44 (0)117 4560633
Email	pioneer-trial@bristol.ac.uk

Study information

Eligibility

Locations

Countries of recruitment

• United Kingdom

Study participating centres

Results and Publications

Study outputs

Editorial Notes

07/10/2024: The recruitment start date was changed from 30/09/2024 to 01/11/2024.
23/07/2024: The recruitment start date was changed from 01/07/2024 to 30/09/2024.
02/05/2024: Internal review.
18/04/2024: ISRCTN received notification of combined HRA/MHRA approval for this trial on 18/04/2024.
19/02/2024: Trial's existence confirmed by NHS HRA.