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

Evaluating Customized Antibiotic Duration (CDA) Strategy in Acute Exacerbations of COPD: Protocol for Randomized Controlled Trial

The goal of this clinical trial is to learn whether a shorter course of antibiotics (7 days) works as well as the usual longer course (14 days) for adults admitted to hospital with a flare-up of chronic obstructive pulmonary disease (COPD), a long-term lung disease. The trial takes place at CDA Hospital Islamabad, Pakistan.

The main questions it aims to answer are:

• Do patients who take antibiotics for 7 days recover as well by Day 30 as patients who take them for 14 days?
• Does the shorter course lead to fewer side effects and less antibiotic use, without more treatment failures, relapses or hospital readmissions? Researchers will compare a 7-day antibiotic course with the usual 14-day course to see if the shorter course is just as effective.

Participants will:

• Be assigned by chance (like flipping a coin) to take antibiotics for either 7 days or 14 days. Their doctor chooses which antibiotic to use.
• Receive all other usual hospital care for their COPD flare-up.
• Have check-ups about 3-5 days, 7 days, 14 days and 30 days after joining the trial, in hospital or by telephone, to record their symptoms, any side effects and any return to hospital.

About 560 adults will take part.

Study Overview

• Status: Not yet recruiting
• Conditions: COPD; Acute Exacerbation of COPD
• Intervention / Treatment: Drug: 7-day antibiotic course; Drug: 14-day antibiotic course

Detailed Description

Background: Antibiotics are routinely given to adults hospitalised with an acute exacerbation of COPD (AECOPD). International guidance (GOLD) advises that treatment should normally last about 5 days, but in many hospitals in Pakistan courses of 14 days remain usual practice. Longer courses increase antibiotic exposure, adverse effects and the risk of antimicrobial resistance, yet there is no randomised evidence from Pakistan on whether a shorter course is as effective for hospitalised patients.

Intervention: The experimental arm receives a 7-day systemic antibiotic course and the active comparator arm the conventional 14-day course. The treating physician chooses the agent, dose and route according to institutional practice and available microbiology, so only the planned duration differs between arms. Duration is counted from the first antibiotic dose for the current exacerbation. All other care, including bronchodilators, corticosteroids, oxygen and ventilatory support, follows usual practice in both arms. The intervention was developed through a three-round Delphi consensus process with prescribers before the trial began.

Procedures: Blood and sputum samples are taken at baseline for culture and susceptibility testing; results may guide a change of agent but do not change the allocated duration. Participants are assessed during treatment (Day 3-5), at Day 7, at Day 14 and at Day 30, in hospital or by telephone. Allocation uses a computer-generated sequence with permuted blocks of variable size, concealed through a web-based randomisation system.

Sample size: Assuming 80% clinical success in both arms, a non-inferiority margin of 10 percentage points, a one-sided alpha of 0.025 and 80% power, 252 evaluable participants per arm are required; allowing for 10% attrition, 560 participants will be enrolled.

Analysis: The primary analysis estimates the risk difference in clinical success at Day 30 (7-day minus 14-day) with a two-sided 95% Miettinen-Nurminen confidence interval. Non-inferiority will be concluded only if the lower confidence limit exceeds -10 percentage points in both the intention-to-treat and per-protocol populations. Full details are given in the study protocol (version 2.0) and statistical analysis plan (version 1.1).

• Study Type: Interventional
• Enrollment (Estimated): 560
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fazal Rabbi, MD; Phone Number: +923035646227; Email: faiz@bjmu.edu.cn

Study Locations

• Pakistan
  • Pakistan
    • Islamabad, Pakistan, Pakistan, 44000
      • CDA Hospital Islamabad
      • Contact: Dr Fazal Rabbi; Phone Number: +923035646227; Email: faiz@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 previous spirometry consistent with COPD.
• A current acute exacerbation of COPD for which the treating physician judges antibiotic therapy to be necessary, with at least two of the three cardinal symptoms (increased dyspnoea, increased sputum volume, increased sputum purulence).
• Able and willing to give written informed consent and to follow the study procedures and follow-up schedule.

Exclusion Criteria:

• A documented infection that requires a defined, longer antibiotic course, such as pneumonia with complications, an exacerbation of bronchiectasis, lung abscess or empyema.
• Need for immediate admission to intensive care or for invasive mechanical ventilation at presentation.
• Severe immunosuppression, for example neutropenia, active malignancy under chemotherapy, organ transplantation or advanced HIV infection.
• Suspected or confirmed pulmonary tuberculosis, or another respiratory infection that needs a different antimicrobial approach.
• Pregnancy or breastfeeding.
• Previous enrolment in this trial, or current participation in another interventional trial in AECOPD.
• Systemic antibiotic treatment for the current exacerbation started more than 48 hours before randomisation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 7-day antibiotic course; Participants receive systemic antibiotic therapy for a total of 7 days, counted from the first dose for the current exacerbation. The treating physician chooses the antibiotic agent, dose and route; all other care follows usual practice.	Drug: 7-day antibiotic course; Systemic antibiotic therapy is given for a total of 7 days, counted from the first dose for the current exacerbation. The agent, dose and route are chosen by the treating physician according to institutional practice, suspected cause and available microbiology; only the planned duration differs from the comparator.
Active Comparator: 14-day antibiotic course; Participants receive systemic antibiotic therapy for a total of 14 days, counted from the first dose for the current exacerbation, which is the usual practice at the study hospital. The treating physician chooses the antibiotic agent, dose and route; all other care follows usual practice.	Drug: 14-day antibiotic course; Systemic antibiotic therapy given for a total of 14 days, counted from the first dose for the current exacerbation, which is usual practice at the study hospital. The agent, dose and route are chosen by the treating physician according to institutional practice, suspected cause and available microbiology; only the planned duration differs from the experimental arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Success at Day 30	Number and proportion of participants with clinical success at Day 30 (±3 days) after randomisation, compared between arms as a risk difference (7-day minus 14-day) with a non-inferiority margin of -10 percentage points. Clinical success requires all of: (a) resolution or substantial improvement of the exacerbation-related signs and symptoms present at baseline (dyspnoea, sputum volume and sputum purulence), judged by the blinded outcome assessor using predefined criteria, with a reduction of at least 2 points from baseline in the COPD Assessment Test score; (b) no additional or alternative systemic antibiotic for a respiratory indication after the allocated course, and no extension of the course because of lack of improvement; (c) no hospital readmission or emergency department visit for AECOPD; and (d) the participant is alive. Participants who do not meet all four criteria are classified as clinical failures.	Day 30 (±3 days) after randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Success at Day 14	Number and proportion of participants with clinical success at Day 14 (±2 days) after randomisation, defined as for the primary outcome, compared between arms as a risk difference.	Day 14 (±2 days) after randomisation
Time to Resolution of Exacerbation Symptoms	Number of days from randomisation to resolution of the exacerbation symptoms present at baseline.	From randomisation up to Day 30
Incidence of Antibiotic-Related Adverse Events and Serious Adverse Events	Number of participants with at least one adverse event or serious adverse event related to antibiotic treatment.	From randomisation up to Day 30
Treatment Failure	Number of participants with treatment failure, defined as the need for additional or alternative systemic antibiotics because of clinical deterioration or lack of improvement, escalation to non-invasive or invasive ventilation or intensive care after Day 3, or death.	From randomisation up to Day 30
Relapse	Number of participants with a new or worsening exacerbation requiring systemic antibiotics or corticosteroids after initial clinical improvement.	From randomisation up to Day 30
Rehospitalisation for Any Cause and for AECOPD	Number of participants readmitted to hospital, reported separately for any cause and for acute exacerbation of COPD.	Within 30 days after randomisation
All-Cause Mortality	Number of participants who die from any cause.	Within 30 days after randomisation
Total Antibiotic Consumption	Total systemic antibiotic consumption per participant, expressed in defined daily doses (DDD).	From randomisation up to Day 30

Collaborators and Investigators

• Sponsor: Capital Development Authority (CDA)
• Investigators: Principal Investigator: Fazal Rabbi, MD, Capital Development Authority (CDA)

Publications and helpful links

General Publications

• Chan AW, Boutron I, Hopewell S, Moher D, Schulz KF, Collins GS, Tunn R, Aggarwal R, Berkwits M, Berlin JA, Bhandari N, Butcher NJ, Campbell MK, Chidebe RCW, Elbourne DR, Farmer AJ, Fergusson DA, Golub RM, Goodman SN, Hoffmann TC, Ioannidis JPA, Kahan BC, Knowles RL, Lamb SE, Lewis S, Loder E, Offringa M, Ravaud P, Richards DP, Rockhold FW, Schriger DL, Siegfried NL, Staniszewska S, Taylor RS, Thabane L, Torgerson DJ, Vohra S, White IR, Hrobjartsson A. SPIRIT 2025 statement: updated guideline for protocols of randomised trials. Lancet. 2025 May 17;405(10491):e19-e27. doi: 10.1016/S0140-6736(25)00770-6. Epub 2025 Apr 28.
• Wang Y, Zijp TR, Bahar MA, Kocks JWH, Wilffert B, Hak E. Effects of prophylactic antibiotics on patients with stable COPD: a systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2018 Dec 1;73(12):3231-3243. doi: 10.1093/jac/dky326.
• Vanoverschelde A, Van Hoey C, Buyle F, Den Blauwen N, Depuydt P, Van Braeckel E, Lahousse L. In-hospital antibiotic use for severe chronic obstructive pulmonary disease exacerbations: a retrospective observational study. BMC Pulm Med. 2023 Apr 25;23(1):138. doi: 10.1186/s12890-023-02426-3.

Study record dates

Study Major Dates

• Study Start (Estimated): October 26, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: July 3, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 16, 2026

Study Record Updates

• Last Update Posted (Actual): October 7, 2026
• Last Update Submitted That Met QC Criteria: October 6, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: COPD; ICU; Pakistan; Antibiotic duration; ACOPD
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: IRB-113-07-08-25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified individual participant data underlying the published results will be made available to researchers on reasonable request to the corresponding author after publication, subject to institutional and ethical approval.

IPD Sharing Time Frame

Beginning after publication of the main trial results, with no fixed end date.

IPD Sharing Access Criteria

Requests should be sent to the lead author and co-author (faiz@bjmu.edu.cn) with a brief research proposal. Data will be shared after approval of the proposal by the investigators and the relevant institutional review boards, and after a data-sharing agreement has been signed.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No