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.

Customised duration of antibiotic strategy appears to be a patient-centred approach that could be effective in avoiding unnecessary antibiotic use without compromising patient outcomes. However, insufficient evidence is available on the safety and efficacy of CAD in hospitals for treating AECOPD. Therefore, the study aims to assess the implementation of the CAD strategy in hospital settings.

Comparators choice The active comparator is a 14-day antibiotic course, representing the entrenched usual-care duration in participating hospitals rather than an internationally endorsed standard. Because the question is whether reduced antibiotic exposure preserves clinical benefit without an unacceptable loss of efficacy, an active-controlled non-inferiority design is appropriate. Framing 14 days as "usual care" (not as a guideline standard) is essential for correct interpretation, given that GOLD recommends 5 days.

Intervention description Participants in the experimental arm will receive a 7-day course, and those in the control arm a 14-day course of the same class of antibiotic. To preserve pragmatism and external validity, the specific agent will be selected by the treating physician according to institutional practice, suspected aetiology, available microbiology and patient factors; only the planned duration differs between arms. The agent, dose, route, frequency and any modification will be recorded on the case report form (CRF). All non-duration components of care - including microbiological sampling, patient education and counselling - will be applied identically in both arms so that the randomised contrast is restricted to treatment duration.

The duration thresholds and supporting clinical materials were informed by a formative consensus process using the Delphi method. Three structured rounds involving approximately 30 experts (prescribers, pharmacists and academics) from participating and reference hospitals (convened in January 2026) were used to agree on the intervention components and supporting materials; items not reaching ≥80% agreement after the third round were discarded. This consensus work informed the design of the intervention, but does not itself constitute a co-intervention that differs between arms-the intervention development strategies with Delphi and expert panellists.

Clinical success is defined as resolution or substantial improvement of signs and symptoms of AECOPD present at baseline, without the need for additional systemic antibiotic therapy, assessed at Day 7 and up to 14 (±2 days) after randomization.

A detailed file is uploaded in the documents section.

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.

Because the two arms differ in treatment duration, blinding of participants and treating clinicians is not feasible, and the trial will be open-label. To limit ascertainment and analysis bias, the trial will follow a prospective, randomised, open-label, blinded-endpoint (PROBE) approach: outcome assessors and the trial statistician will be blinded to allocation. As the trial is open-label, formal emergency unblinding procedures are not required.