Evaluating Customized Antibiotic Duration (CDA) Strategy in Acute Exacerbations of COPD

Introduction Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a major source of morbidity, mortality and antibiotic consumption worldwide. Although international guidance now recommends short antibiotic courses for AECOPD, prescribing in many tertiary hospitals in Pakistan is neither standardised nor guideline-concordant, and prolonged courses remain common. Reducing unnecessary antibiotic exposure is a recognised strategy to contain antimicrobial resistance (AMR), but locally generated evidence on the safety and efficacy of shorter courses is lacking. Method and analysis This multicentre, prospective, parallel-group, open-label, randomised controlled non-inferiority trial will compare a 7-day antibiotic regimen (experimental) with the locally conventional 14-day regimen (active control) in adults hospitalised with AECOPD requiring antibiotics. Participants will be randomised 1:1 with allocation stratified by site. The primary outcome is clinical success at Day 30 after randomisation, defined as resolution or substantial improvement of baseline exacerbation symptoms without need for additional systemic antibiotics, major treatment modification, or readmission for treatment failure. Assuming 80% clinical success in both arms, a non-inferiority margin of 7-or8 percentage points, one-sided α = 0.025 and 80% power, 251 participants per arm are required; allowing for 10% attrition, the target is 558 participants (279 per arm). The primary analysis will estimate the between-group risk difference with its two-sided 95% confidence interval in both the intention-to-treat and per-protocol populations; non-inferiority will be concluded if the lower confidence limit lies above 10 percentage points in both populations. Secondary outcomes include time to symptom resolution, antibiotic-related adverse events, treatment failure, relapse, rehospitalisation, all-cause mortality and antibiotic consumption. Ethics and dissemination The ethical approval has been obtained from the Institutional Review Board of the hospital (IRB-113-07-08-25). The outcomes and findings will be disseminated through peer-reviewed journal articles and will engage policymakers on various forums, including clinical settings. Discussion The optimal duration of antibiotic therapy for AECOPD remains uncertain. Shorter treatment courses may reduce antibiotic exposure, adverse events, and the development of AMR. This trial will compare the effectiveness and safety of 7-day and 14-day antibiotic regimens in patients with AECOPD. The findings may help inform clinical guidelines and promote more appropriate antibiotic use.

Inclusion Criteria: * Adults aged 18 years or older * Physician-diagnosed COPD, confirmed by post-bronchodilator spirometry (FEV1/FVC \< 0.70) where available, or by documented prior spirometry consistent with COPD * Current acute exacerbation of COPD requiring antibiotic therapy in the judgment of the treating physician, with at least two cardinal symptoms (increased dyspnoea, sputum volume, or sputum purulence) * Able and willing to provide written informed consent and to comply with study procedures and follow-up Exclusion Criteria: * Documented infection requiring a defined prolonged antibiotic course (e.g. pneumonia with complications, bronchiectasis exacerbation, lung abscess, empyema) * Need for immediate intensive care admission or invasive mechanical ventilation at presentation * Severe immunosuppression (e.g. neutropenia, active malignancy on chemotherapy, organ transplantation, advanced HIV) * Suspected or confirmed pulmonary tuberculosis or another respiratory infection requiring a different antimicrobial approach * Pregnancy or breastfeeding * Prior enrolment in this trial or current participation in another interventional AECOPD trial.