Optimising the use of azithromycin antibiotic to reduce Bronchiectasis flare-ups

Plain English summary of protocol

Background and study aims
People living with bronchiectasis may experience worsening symptoms such as shortness of breath, cough and wheezing in addition to changes that may be expected for having bronchiectasis. The worsening of symptoms is called exacerbation or flare-up and can be debilitating and frightening, requiring additional treatment, often with azithromycin. This is an antibiotic medicine that also has anti-inflammatory properties. It is prescribed as long-term prevention to reduce the risk of flare-ups. Some people may be affected by side effects from azithromycin. Antibiotic resistance is another concern, especially when using azithromycin for prevention rather than to treat active infection. It is currently unknown whether to advise people to stop taking azithromycin once bronchiectasis has stabilised. It is also unknown if azithromycin is more effective in some people or more likely to cause side effects in others. Given these uncertainties, it is challenging to know how best to use azithromycin in managing bronchiectasis. Azithromycin is a valuable antibiotic. To maintain its benefit while avoiding unnecessary side effects it is necessary to reduce the chances of bacteria becoming resistant to it. This trial aims to establish the effects of stopping azithromycin in people whose bronchiectasis has stabilized after taking it for at least 3 months. It will compare continuing azithromycin with stopping it completely, examining the effects of these two treatments on flare-ups, symptoms, and quality of life, and identifying factors that may affect individual responses.

Who can participate?
Patients aged 16 years old and over with clinically stable bronchiectasis and prescribed prophylactic azithromycin or an equivalent long-term macrolide for at least 90 days in the past 12 months due to reduce the risk of bronchiectasis exacerbations

What does the study involve?
In this study, patients will continue taking azithromycin or switch to a placebo for 12 months. The dosage will match what they were already taking, which could be 250mg once a day three times a week, 500mg once a day three times a week, or 250mg once a day every day. The medication will be taken orally.

What are the possible benefits and risks of participating?
Participants may have no personal benefit from taking part in this trial. They will have trial-related monitoring and interactions with healthcare professionals during the trial. They may experience fewer azithromycin-related side effects. However, the results from this trial will benefit patients with bronchiectasis in the future because it will help the researchers know how best to use azithromycin long-term treatment for people with bronchiectasis. Information from the trial will also help the researchers better understand frailty in bronchiectasis from the data that are collected as participants will be followed up. The researchers also hope to gain information about the best approaches to aid recruitment into clinical trials.

Participants may experience more flare-ups of their bronchiectasis or may experience side effects from the azithromycin which will be closely monitored by the trial teams at participating sites. If they experience 3 or more flare-ups within the year, the participant will be advised to stop the trial medication and possibly re-start their standard azithromycin treatment (clinician's decision).

Although the participants would have been on azithromycin for at least 90 days before recruitment to the trial, there may be some burden linked to participants being asked to self-administer oral medication. There may be a risk that tablets may not be taken (underdose) or taken too much (overdose). This will be mitigated by regular checks of compliance over the telephone/visits. The regimen will also match that of the patient's routine prescription for the IMP that they had been taking for at least the previous 90 days to minimise any further burden on the participants.

There may be a risk with IMP delivery for participants unable to collect the IMP at baseline / 6 months visit whereby there is either a delay of the participant receiving the IMP, or not receiving the IMP at all. This could be due to delivery issues, the participant not being at home, or someone else taking the delivery, etc. This will be mitigated by trial team contact with the participant within a week of the participant's enrolment to the trial and the 6 months visit.

If trial visits cannot coincide with the participant's standard of care (SoC) appointments, there may be the burden of additional visits to the hospital. This burden will be mitigated by carrying out those visits remotely.

Where is the study run from?
Newcastle University, UK

When is the study starting and how long is it expected to run for?
March 2025 to May 2029

Who is funding the study?
NIHR Health Technology Assessment Programme (HTA)

Who is the main contact?
Prof Anthony De Soyza, anthony.de-soyza@newcastle.ac.uk

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• Scotland
• United Kingdom
• Wales

Study participating centres

Sponsor information

Newcastle upon Tyne Hospitals NHS Foundation Trust
Hospital/treatment centre

Level 1, Regent Point, Regent Farm Road, Gosforth
Newcastle Upon Tyne
NE3 3HD
England
United Kingdom

Phone	+44 191 2826774
Email	tnu-tr.sponsormanagement@nhs.net
Website	http://www.newcastle-hospitals.org.uk/
"ROR"	https://ror.org/05p40t847

Funders

Funder type

Government

Results and Publications

Editorial Notes

29/04/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 29/04/2025
15/03/2025: Study's existence confirmed by Health Research Authority (HRA) (UK)