Investigating the effect of azithromycin on gullet function in patients with long-term respiratory disease
| ISRCTN | ISRCTN16059833 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16059833 |
| IRAS number | 1006318 |
| ClinicalTrials.gov number | NCT05469555 |
| Secondary identifying numbers | IRAS 1006318 |
- Submission date
- 16/09/2022
- Registration date
- 16/12/2022
- Last edited
- 19/06/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
Symptoms such as cough, wheeze, and breathlessness are among the most common reasons for patients to visit their general practitioner or emergency department in the United Kingdom, accounting for up to 20% of healthcare visits. Such symptoms are known to have a profound impact on the ability of such patients to live a fulfilled life, as they can often render people unable to work and socialise. Patients are often left with lasting symptoms despite being treated with all currently recommended therapies, suggesting that there is ample reason to keep searching for new treatments for patients with chronic lung disease.
Azithromycin is a type of antibiotic which has been found to improve symptoms and reduce flare-ups of common diseases such as asthma and chronic obstructive pulmonary disease (COPD). The reason why it works is still unclear. Many people believe in one of two theories, either that it decreases the number of bacteria in the lungs or that it reduces inflammation in the lungs and the upper airways. Neither of these theories is proven and there has been a different mechanism suggested, although it has been much less studied. Azithromycin is thought to encourage the body to move food and fluid through the gut more quickly, and this may help to prevent small food particles and stomach to reflux into the airways. It has been shown that lung damage can occur when gut contents enter the airways, which may contribute to the symptoms of patients with chronic lung disease.
Who can participate?
Adult patients diagnosed with a respiratory condition
What does the study involve?
In this study, we will test the effect of azithromycin on the gut in patients with chronic lung diseases. We will measure the strength of a patient's swallow by measuring the pressures in their gullet, using high-resolution oesophageal manometry (HROM), before and after treatment, in people being started on azithromycin as part of their routine care. We will also measure the effect that azithromycin has on their symptoms and observe whether there is a relationship between the strength of their swallow and their symptoms.
At the end of this study, we will hope to better understand the way in which azithromycin helps to improve the symptoms of patients with chronic lung diseases. We also hope to open the door to investigating the effect of other drugs that improve gut function in patients with chronic lung diseases.
What are the possible benefits and risks of participating?
There will be the inconvenience of travelling to the clinical trials unit on 3 separate occasions, we will attempt to assuage this by offering a broad range of time options for participants to attend and helping them with travel arrangements whenever possible. Travel expenses will be reimbursed for up to £10 per study visit.
HROM is generally seen as an uncomfortable procedure and can sometimes give patients a runny nose or sore throat, advice will be given to help these symptoms. The investigations will be carried out by expert technicians with many years of experience, minimising any risks.
We will be asking participants to carry around a mobile cough recording device, either a smartwatch or a dedicated mobile phone device, which may be cumbersome. We endeavour to provide all participants with smartwatches as this will minimise the impact on participants' daily lives. We will give all participants training in how to use and carry the devices in order for them to be as discrete as possible to minimise the interruption to their normal daily life.
Where is the study run from?
Hull University Teaching Hospitals NHS Trust, Castle Hill Hospital (United Kingdom)
When is the study starting and how long is it expected to run for?
September 2022 to August 2024
Who is funding the study?
Hull University Teaching Hospitals NHS Trust (United Kingdom)
Who is the main contact?
Dr Dominic Sykes, dominic.sykes2@nhs.net
Contact information
Scientific
R&D
First floor
Castle Hill Hospital
Cottingham
HU16 5JQ
United Kingdom
| Phone | +44 (0)1482 461903 77 |
|---|---|
| james.illingworth3@nhs.net |
Scientific
Academic Respiratory medicine
Daisy Building
Castle Hill Hospital
Cottingham
HU16 5JQ
United Kingdom
| Phone | +44 (0)1482 461795 77 |
|---|---|
| dominic.sykes2@nhs.net |
Study information
| Study design | Randomized 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 to request a participant information sheet |
| Scientific title | Exploring the effect of azithromycin on oesophageal motility and respiratory symptoms in patients with chronic respiratory disease: a prospective observational study |
| Study objectives | Azithromycin (an antibiotic) improves symptoms and reduces flare-ups of diseases such as asthma and chronic obstructive pulmonary disease (COPD). The reason why it works is unclear. Many people believe that it either decreases the number of bacteria in the lungs or reduces inflammation in the lungs and the upper airways. Neither theory is proven. Another possible mechanism that has been much less studied is that azithromycin encourages the body to move food and fluid through the gut more quickly, thus preventing reflux and aspiration of small food particles and stomach acid. It has been shown that lung damage can occur when gut contents enter the airways, which may contribute to chronic lung disease patients’ symptoms In this study, we will test the effect of azithromycin on the gut in patients with chronic lung diseases. We will measure the strength of a patient's swallow by measuring the pressures in their gullet, using high-resolution oesophageal manometry (HROM), before and after To display the effect of azithromycin on symptoms in patients with chronic respiratory disease and how this relates to an improvement in oesophageal function. |
| Ethics approval(s) | 1. Approved 15/12/2022, MHRA (10 South Colonnade, Canary Wharf, London, E14 4PU, UK; +44(0)20 3080 6000; info@mhra.gov.uk), ref: CTA 21411/0261/001-0001 2. Approved 15/12/2022, North East - Newcastle & North Tyneside 2 Research Ethics Committee (NHS BT Blood Donor Centre, Holland Drive, Newcastle upon Tyne, Tyne and Wear, NE2 4NQ, UK; +44 (0)2071048086, (0)2071048140; newcastlenorthtyneside2.rec@hra.nhs.uk), ref: 22/NE/0194 |
| Health condition(s) or problem(s) studied | Ashtma, cough, lung fibrosis, COPD |
| Intervention | All patients who are being started on azithromycin as part of routine clinical care will be investigated with high-resolution oesophageal manometry prior to the commencement of azithromycin. All patients will then receive 1 month of azithromycin 250 mg OD treatment before having a second high-resolution oesophageal manometry investigation performed. At that point, participation in the trial is finished. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Azithromycin |
| Primary outcome measure | 1. Eligibility to consent ratio, defined as the ratio of participants deemed eligible to participate in the study to the number of those who provide consent to take part, measured using an examination of recruitment records i.e. looking at how many patients were approached to how many patients provided informed consent at 1 year 2. Recruitment rate, defined as the number of participants successfully recruited per month, measured using recruitment records i.e. looking at how many patients were recruited to the study each month at 1 year 3. Participant retention to follow-up, defined as the proportion of those participants who consent to take part that complete all study measures to follow-up, measured using the patient database and recording how many patients completed all study measures to 30 days at 1 year 4. Acceptability of assessment, defined as the proportion of participants who judge the study investigations, principally high-resolution oesophageal manometry (HROM), to be acceptable measured using the study experience questionnaire at 1 year |
| Secondary outcome measures | 1. Distal contractile integrity, defined as the effect of azithromycin on the contraction vigour and swallow coordination, measured using high-resolution oesophageal manometry (HROM) before and 1 month after initiation of azithromycin as part of routine clinical care. Measured in mmHg/sec/cm. 2. Lower oesophageal sphincter pressure, defined as the effect of azithromycin on the pressure of the lower oesophageal sphincter as measured using HROM before and 1 month after initiation of azithromycin as part of routine clinical care. Measured in mmHg. 3. Distal latency, defined as the effect of azithromycin on the timeframe of the wave from the beginning of the swallow to an inflection of the peristaltic axis, measured using HROM before and 1 month after initiation of azithromycin as part of routine clinical care. Measured in seconds. 4. Integrated relaxation pressure, defined as the effect of azithromycin on the oesophageal pressure topography metric that is used for assessing the adequacy of oesophagogastric junction relaxation, measured using HROM before and 1 month after initiation of azithromycin as part of routine clinical care. Measured in seconds. 5. Chicago Classification version 4.0, defined as a composite classification based on all HROM measurements at 1 month 6. Symptoms of reflux measured using the Hull Airway Reflux questionnaire, a Likert scale questionnaire at 1 month 7. Symptom burden measured using a 5-point Likert validated tool assessing breathlessness, cough, and sputum scale at 1 month 8. Breathlessness measured using the MRC dyspnoea scale at 1 month 9. Cough severity measured using a visual analogue scale at 1 month 10. Symptom burden measured using a COPD Assessment test (COPD patients only) at 1 month 11. Symptom burden measured using an Asthma control questionnaire (asthma patients only) at 1 month 12. Breathlessness severity measured using a Numerical rating scale at 1 month 13. Impact of cough on physical, social, and psychological welfare of the patient measured using the Leicester Cough Questionnaire at 1 month 14. Impact of overall health, daily life, and well-being in patients with obstructive airways disease measured using the St. George's Respiratory Questionnaire at 1 month 15. Impact of interstitial lung disease on quality of life and health status measured using the King's Brief Interstitial Lung Disease Questionnaire (interstitial lung disease patients only) at 1 month 16. Relationship between oesophageal motility and symptoms examined measured using statistical analysis at 1 month |
| Overall study start date | 13/09/2022 |
| Completion date | 01/08/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 30 |
| Total final enrolment | 30 |
| Key inclusion criteria | 1. Males and females aged ≥18 years 2. Have a diagnosis of chronic respiratory disease (COPD, asthma, interstitial lung disease, chronic cough, cystic fibrosis, and/or bronchiectasis) confirmed by a respiratory consultant 3. Exhibit symptoms consistent with airway reflux, demonstrated by a score ≥14 on the Hull Airways Reflux Questionnaire 4. Are being initiated on azithromycin as part of routine clinical care, as judged by their usual respiratory clinician. This will include all common treatment regimes, 250mg once daily, 250mg three times per week, and 500mg three time per week. 5. Are willing and able to consent to all study procedures |
| Key exclusion criteria | 1. Previous treatment with long-term macrolides in the past 3 months 2. Unable to be investigated with HROM due to contraindications such as anatomical abnormalities or diseases of the oesophagus or unwilling/ unable to be investigated with HROM based on the clinical judgement of the investigators due to the severity of lung disease 3. Have another cardiorespiratory cause for their symptoms (such as heart failure or lung cancer) 4. Women of childbearing potential not using effective means of contraception 5. Are unable or unwilling to consent to or complete the study procedures |
| Date of first enrolment | 06/01/2023 |
| Date of final enrolment | 07/05/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Cottingham
HU16 5JQ
United Kingdom
Sponsor information
Hospital/treatment centre
1st floor
Daisy building
Castle Hill Hospital
Cottingham
HU16 5JQ
England
United Kingdom
| Phone | +44 (0)1482 461903 |
|---|---|
| hyp-tr.development.research@nhs.net | |
| Website | http://www.nhs.uk/Services/hospitals/Overview/DefaultView.aspx?id=1998 |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | 01/10/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | 1. Peer-reviewed scientific journals 2. Conference presentation 3. Primary data will be anonymised and will be available on request |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from: Dominic Sykes dominic.sykes2@nhs.net Excel file Shared with any research professionals by Dr Dominic Sykes. For secondary analysis or as part of meta-analyses. All data will be anonymised. No ethical or legal restrictions. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 4 | 18/01/2023 | 11/12/2023 | No | No |
Additional files
Editorial Notes
19/06/2024: The recruitment end date was changed from 01/06/2024 to 07/05/2024. Total final enrolment added.
11/12/2023: The following changes have been made:
1. The recruitment end date has been changed from 01/12/2023 to 01/06/2024.
2. The overall study end date has been changed from 01/01/2024 to 01/08/2024 and the plain English summary updated accordingly.
3. The intention to publish date has been changed from 01/09/2024 to 01/10/2024.
17/01/2023: The following changes were made to the trial record:
1. The participant level data sharing statement was added.
2. The ClincialTrials.gov number was added.
16/12/2022: ISRCTN received notification of combined HRA/MHRA approval for this trial on 16/12/2022
16/09/2022: Trial’s existence confirmed by the HRA.
