Optimising Azithromycin Prevention Treatment in COPD to Reduce Exacerbations

NCT05772013 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: CCTU0333
• Study Type: interventional
• Target: 1,311
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; Azithromycin; Chemoprophylaxis

Outcome Measures

Primary Outcomes (1)

• COPD exacerbation

  Time to first COPD exacerbation.

  Throughout the entire trial follow-up of 24 months

Secondary Outcomes (11)

• Number and rate of exacerbations

  Throughout the entire trial follow-up of 24 months

• Exacerbation-free period

  Throughout the entire trial follow-up of 24 months

• Treatment for respiratory indication

  Throughout the entire trial follow-up of 24 months

• CAT Score

  Throughout the entire trial follow-up of 24 months

• Cough visual analogue scale (VAS) score

  Throughout the entire trial follow-up of 24 months

Study Arms (3)

Continuous azithromycin

ACTIVE COMPARATOR

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.

Drug: Azithromycin Pill

Seasonal azithromycin

OTHER

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).

Drug: Azithromycin Pill; Drug: Placebo

Complete Discontinuation of azithromycin

PLACEBO COMPARATOR

Participants will take continuous matched placebo throughout the trial.

Drug: Placebo

Interventions

Azithromycin Pill DRUG

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).

Continuous azithromycin; Seasonal azithromycin

Placebo DRUG

The placebo tablets will be matched in appearance, taste and smell to the azithromycin tablets.

Complete Discontinuation of azithromycin; Seasonal azithromycin

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able and willing to provide informed consent.
• 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.

You may not qualify if:

• Known hypersensitivity to any of the trial drugs or excipients.
• Current breast feeding, pregnancy or planned pregnancy during the trial.
• 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.

Sponsors & Collaborators

• Dr Ian B Wilkinson: lead
• University of Aberdeen: collaborator
• NHS Greater Glasgow and Clyde: collaborator
• University of East Anglia: collaborator
• Nottingham City Hospital: collaborator
• Swansea University: collaborator
• Newcastle University: collaborator
• University of Cambridge: collaborator
• NHS Sunderland Clinical Commissioning Group: collaborator
• Liverpool School of Tropical Medicine: collaborator
• Royal Brompton & Harefield NHS Foundation Trust: collaborator
• University College London Hospitals: collaborator
• Liverpool Heart and Chest Hospital NHS Foundation Trust: collaborator
• Imperial College London: collaborator
• Red Graphic: collaborator
• Eramol (UK) Ltd.: collaborator
• WGK Clinical Services Ltd.: collaborator
• Sealed Envelope Ltd.: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

Cambridge University Hospital NHS Trust, Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Ian B Wilkinson

  University of Cambridge & University of Cambridge NHS Foundation Trust

  STUDY DIRECTOR

Central Study Contacts

Zehra T Yilmaz

CONTACT

+44 (0)1223 256599; zehra.yilmaz@nhs.net

Heike Templin

CONTACT

+44 (01223 250874; heike.templin@nhs.net

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: OPACE is a double-blind, adaptive design, placebo-controlled phase IV randomized controlled trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Therapeutics

Study Record Dates

• First Submitted: February 27, 2023
• First Posted: March 16, 2023
• Study Start: March 5, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: April 3, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

GB (1)