Optimising Azithromycin Prevention Treatment in COPD to Reduce Exacerbations
NCT ID: NCT05772013
Last Updated: 2024-04-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE4
1311 participants
INTERVENTIONAL
2024-03-05
2028-11-30
Brief Summary
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It is currently unclear as to whether people should be advised to stop taking azithromycin once COPD has stabilised, or to stop it over the summer when fewer flare-ups happen. It is also not known 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 COPD. Azithromycin is a valuable antibiotic, and should be prescribed where it has benefit but avoid unnecessary side effects and reduce the chances of bacteria becoming resistant to it.
The purpose of this trial is to be able to gain results to answer these questions, and to establish the effects of stopping azithromycin in people whose COPD has stabilised, who have been taking it for at least 3 months. This trial will compare continuing azithromycin with stopping it completely, or stopping over the summer only, continuing over the winter. The investigators will compare the effects of these three treatments in the trial on flare-ups, symptoms and quality of life, and find out what factors may affect how individual participants respond to them.
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Detailed Description
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Aim: To evaluate the benefits and risks of complete or seasonal discontinuation of azithromycin chemoprophylaxis vs continued treatment in people with stable COPD at high risk of exacerbations and assess effects in participant subgroups.
Methods: Design: A randomised double-blinded, non-inferiority, adaptive-design pragmatic trial of 3 parallel arms (complete discontinuation, vs seasonal discontinuation vs continued azithromycin as standard of care), to test the strategy of discontinuation of prophylactic azithromycin in participants with stable COPD at high risk of exacerbations. Internal pilot to evaluate recruitment will run for 9 months from first participant first visit (FPFV).
Randomisation allocation will be 1:1:1. Adaptive design means a treatment arm can be dropped if futile at interim analysis, but remaining arms continue.
Setting: General Practitioner (GP) practices, specialist community clinics, hospitals.
Target population: Stable COPD participants prescribed azithromycin ≥3 months to reduce risk of COPD exacerbations.
Interventions assessed: Complete discontinuation of azithromycin (matched placebo), seasonal discontinuation (azithromycin October-March, matched placebo April-September), continued azithromycin (standard of care).
Trial duration and procedures: Median follow up will be 24 months. Participants will have up to 3 visits - baseline, 12 months, 24 months/end of trial, which may coincide with standard of care visits and be in-person or remote depending on participant's individual preference. Telephone follow-up will be conducted at 1 week, 3 months, 6 months, and 18 months. All participants will have active follow up until study end, even if primary endpoint met. If participants have 3 or more exacerbations/year they will be advised to stop their trial medication. Participants may restart regular azithromycin prescription after stopping trial medication if advised by their GP/specialist. Secondary outcomes will be collected over the entire trial period and therefore may include evaluation both on and off trial medication.
Outcome measures:
Primary endpoint: Time to first exacerbation (TTFE) necessitating additional treatment with antibiotics and/or corticosteroids.
Key secondary endpoints (collected over entire trial)
1. Number/rate and severity of exacerbations, length of exacerbation-free status
2. Health related quality of life measured by change in the EuroQol-5 dimension
3. Symptoms (COPD assessment tool (CAT) score and cough)
4. Side effects
5. Mortality
6. Cost effectiveness from National Health Service (NHS) perspective.
Sample size: 1311 participants (437 per arm). Assuming a median TTFE of 150 days and non-inferiority threshold of 30 days shorter, equates to the threshold on the hazard ratio scale of 1.25. Sample size is based on 90 percent power for two non-inferiority comparisons (seasonal and placebo compared with continuous as standard treatment), at 2.7 percent significance using a Cox proportional hazards model. Pre-specified factors for subgroup analysis include exacerbation history, forced expiratory volume at one second (FEV1 percentage) predicted, current/ex-smoking status, COPD Assessment Tool (CAT) score, age, blood eosinophils.
Conclusion:
This pragmatic, real world trial aims to answer the uncertainties regarding prophylactic azithromycin use in COPD.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Continuous azithromycin
Participants in this arm will continue with their standard of care (i.e. continuous dose of azithromycin according to their standard prescription) throughout the trial.
Azithromycin Pill
Participants will take azithromycin according to their standard of care prescription.
If the participant is on the seasonal azithromycin treatment arm, they will only take azithromycin during the winter months (October-March) followed by matched placebo (April-September).
Seasonal azithromycin
Azithromycin will be taken by participants during the autumn-winter (October - March).
Matched placebo will be taken by the participants in the spring-summer (April - September).
Azithromycin Pill
Participants will take azithromycin according to their standard of care prescription.
If the participant is on the seasonal azithromycin treatment arm, they will only take azithromycin during the winter months (October-March) followed by matched placebo (April-September).
Placebo
The placebo tablets will be matched in appearance, taste and smell to the azithromycin tablets.
Complete Discontinuation of azithromycin
Participants will take continuous matched placebo throughout the trial.
Placebo
The placebo tablets will be matched in appearance, taste and smell to the azithromycin tablets.
Interventions
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Azithromycin Pill
Participants will take azithromycin according to their standard of care prescription.
If the participant is on the seasonal azithromycin treatment arm, they will only take azithromycin during the winter months (October-March) followed by matched placebo (April-September).
Placebo
The placebo tablets will be matched in appearance, taste and smell to the azithromycin tablets.
Eligibility Criteria
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Inclusion Criteria
* Have an established clinical diagnosis of COPD and be receiving prophylactic azithromycin for ≥ (at least) 3 months to reduce COPD exacerbations.
* Have a self-reported smoking history of ≥ (at least) 10 pack years.
* Be aged \>= 40 years.
* Have clinically stable COPD, i.e. no COPD exacerbation for at least 6 weeks.
Exclusion Criteria
* Current breast feeding, pregnancy or planned pregnancy during the trial.
* Any medical history or clinically relevant abnormality that makes participant ineligible for inclusion because of a safety concern relating to continuing or discontinuing azithromycin or other considerations.
* Known immunodeficiency requiring immunoglobulin/specific antibody therapy.
* Azithromycin prophylaxis prescribed for non-COPD condition.
* Active participation in COPD Clinical Trial of an Investigational Medicinal Product (CTIMP).
Electrocardiograms (ECGs) will not be a trial assessment nor entry requirement.
40 Years
ALL
No
Sponsors
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University of Aberdeen
OTHER
NHS Greater Glasgow and Clyde
OTHER
University of East Anglia
OTHER
Nottingham City Hospital
UNKNOWN
Swansea University
OTHER
Newcastle University
OTHER
University of Cambridge
OTHER
NHS Sunderland Clinical Commissioning Group
UNKNOWN
Liverpool School of Tropical Medicine
OTHER
Royal Brompton & Harefield NHS Foundation Trust
OTHER
University College London Hospitals
OTHER
Liverpool Heart and Chest Hospital NHS Foundation Trust
OTHER
Imperial College London
OTHER
Red Graphic
UNKNOWN
Eramol (UK) Ltd.
UNKNOWN
WGK Clinical Services Ltd.
UNKNOWN
Sealed Envelope Ltd.
UNKNOWN
National Institute for Health Research, United Kingdom
OTHER_GOV
Dr Ian B Wilkinson
OTHER
Responsible Party
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Dr Ian B Wilkinson
Professor of Therapeutics
Principal Investigators
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Ian B Wilkinson
Role: STUDY_DIRECTOR
University of Cambridge & University of Cambridge NHS Foundation Trust
Locations
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Cambridge University Hospital NHS Trust, Addenbrookes Hospital
Cambridge, , United Kingdom
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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CCTU0333
Identifier Type: -
Identifier Source: org_study_id
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