Ignite Creation Date:
2024-05-06 @ 6:46 PM
Last Modification Date:
2024-10-26 @ 2:54 PM
Study NCT ID:
NCT05772013
Status:
RECRUITING
Last Update Posted:
2024-04-03
First Post:
2023-02-27
Brief Title:
Optimising Azithromycin Prevention Treatment in COPD to Reduce Exacerbations
Sponsor:
Dr Ian B Wilkinson
Organization:
Cambridge University Hospitals NHS Foundation Trust
Study Overview
Official Title:
Optimising Azithromycin Prevention Treatment in COPD to Reduce Exacerbations OPACE A Double Blind Adaptive Design Pragmatic Phase IV Randomised Controlled Trial
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
OPACE
Brief Summary:
People living with chronic obstructive pulmonary disease COPD may experience worsening of symptoms such as shortness of breath cough and wheezing in addition to changes that may be expected for having COPD The worsening of symptoms is called exacerbations or flare-ups 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 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
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
Detailed Description:
Background Prophylactic azithromycin is recommended as a treatment to reduce the risk of chronic obstructive pulmonary disease COPD exacerbations in people with COPD at high risk of exacerbations In clinical practice there is much uncertainty in how to optimally use this valuable treatment in managing COPD It is unknown whether azithromycin is effective beyond one-year of treatment what happens when azithromycin is discontinued following a period of use or temporarily discontinued over the summer when there are fewer exacerbations Whether there are differences in treatment responsiveness between subgroups of people with COPD is also uncertain
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 111 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 monthsend of trial which may coincide with standard of care visits and be in-person or remote depending on participants 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 exacerbationsyear they will be advised to stop their trial medication Participants may restart regular azithromycin prescription after stopping trial medication if advised by their GPspecialist 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 andor corticosteroids
Key secondary endpoints collected over entire trial
1 Numberrate 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 125 Sample size is based on 90 percent power for two non-inferiority comparisons seasonal and placebo compared with continuous as standard treatment at 27 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 currentex-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
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 111 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 monthsend of trial which may coincide with standard of care visits and be in-person or remote depending on participants 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 exacerbationsyear they will be advised to stop their trial medication Participants may restart regular azithromycin prescription after stopping trial medication if advised by their GPspecialist 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 andor corticosteroids
Key secondary endpoints collected over entire trial
1 Numberrate 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 125 Sample size is based on 90 percent power for two non-inferiority comparisons seasonal and placebo compared with continuous as standard treatment at 27 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 currentex-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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None