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. 2019 May 24;2019(5):CD013024. doi: 10.1002/14651858.CD013024.pub2

Brill 2015.

Methods Design: single‐centre, single‐blind, randomised placebo‐controlled trial in the UK
Duration: 13 weeks
Setting: hospital outpatients
Participants Population: 99 stable participants recruited from primary (local general practices and pulmonary rehabilitation groups) and secondary care (hospital outpatient clinics and local research cohorts)
Baseline characteristics: mean age: 69.4 years, current smokers (n): 41/99, mean pack years: 53, mean number of exacerbations in the previous year (self‐reported): 2.2, mean ICS use (n): 17/99, mean FEV1% predicted: 50.5%, FEV1:FVC ratio: 0.50
Inclusion criteria: age ≥ 45 years at screening, with chronic bronchitis, spirometry confirmed COPD as FEV1 < 80% predicted with FEV1:FVC ratio < 0.7 and history of smoking or other plausible irritant exposure, chronic sputum production (expectoration of sputum on most days), able to give informed consent and able to complete symptom questionnaires and a daily diary card
Exclusion criteria: other significant respiratory disease, COPD exacerbation four weeks prior to randomisation, clinically significant hepatic or renal impairment on screening blood tests, evidence of tuberculosis on screening sputum sample at recruitment, uncontrolled hypertension, prolonged QT on electrocardiogram or history of long QT syndrome, already taking long‐term antibiotics for any reason or any other contraindicated medication, hypersensitivity to any trial antibiotics
Interventions

  1. Moxifloxacin (pulsed; 400 mg for 5 days every 4 weeks)

  2. Doxycycline (continuous; 100 mg daily)

  3. Azithromycin (intermittent; 250 mg 3 times per week)

  4. Placebo (1 tablet daily; not included in this review)
Outcomes

  1. Bacterial load (change in sputum bacterial load)

  2. Lung function (change in FEV1)

  3. Health status (total SGRQ score)

  4. Adherence to therapy

  5. Exacerbations (number of participants with one or more exacerbations)

  6. Adverse events


We were only able to report the number of participants with one or more exacerbations as other outcome results were reported as change from baseline relative to the placebo group.
Notes Funding: National Institute for Health Research (NIHR)
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Internet randomisation was performed using a computer‐generated permuted block system of variable sizes (sealed envelope, UK)
Allocation concealment (selection bias) Low risk Internet randomisation was performed using a computer‐generated permuted block system of variable sizes (sealed envelope, UK)
Blinding of participants and personnel (performance bias) 
 All outcomes Unclear risk Patients remained blinded to treatment allocation. It was not clear if study personnel were blinded. The study is described as single‐blind.
Blinding of outcome assessment (detection bias) 
 All outcomes Unclear risk No description of outcome assessor blinding, although blinded participants assessed outcomes such as quality of life
Incomplete outcome data (attrition bias) 
 All outcomes Low risk Dropout low and balanced. All participants accounted for in the flow diagram
Selective reporting (reporting bias) Low risk Planned outcomes according to trial
Other bias Unclear risk Imbalance in baseline characteristics may affect the study results