Title: A Randomised Double-Blind Placebo-Controlled Study to Evaluate the Efficacy of Oral Azithromycin as a Supplement to Standard Care for Adult Patients with Acute Exacerbations of Asthma
Funder: Department of Health (England)

Abstract: Design: Randomised double-blind placebo-controlled study.Population: Adults with a history of asthma presenting within 24 hrs (of initial presentation requesting acute medical care) with an acute exacerbation of asthma (increased wheeze dyspnoea and/or cough with reduced Peak Expiratory Flow - PEF). Full inclusion/exclusion criteria are provided in the protocol.Intervention: Azithromycin 500mg or placebo once daily (OD) for 3 days.Outcomes: Primary: diary card asthma symptom score assessed at 10 days.Secondary: asthma symptoms lung function and quality of life assessed at 5 & 10 days time to 50% reduction in symptoms time trends in primary and secondary outcomes over the exacerbation time course up to 10 days.Assessments and follow up: The assessments that will be carried out on patients are diary card summary symptom score pulmonary function tests quality of life questionnaires nasal mucus/sputum standard bacterial culture respiratory virus atypical bacterial PCR panel serological status for atypical bacterial infection. The assessments will take place at follow up visits for the patients at 5 and 10 days after randomisation with a final convalescent follow up appointment at 42 days following randomisation.Sample size: 380 patients. The sample size calculation is based on the primary outcome in TELICAST: our previous study found mean decreases in symptom score of 1.3 in treatment group and 1 in the control group resulting in the clinically significant difference of -0.3 (SD 0.783) between the groups at 10 days (end of treatment). Using a two-sided t-test at 1% significance level with 80% power we would need 161 patients in each group to be able to detect the same difference in asthma scores between the groups. The significance level of 1% in the above calculation was chosen to provide additional certainty in the primary outcome and to give extra power to the planned exploratory subgroup analyses. Taking into account the drop-out rate of 15% in the study we propose to recruit 190 patients in each arm of the study. To be able to run the trial within the project timelines we have recruited 10 centres.Statistical analysis: Primary efficacy endpoints will be analysed using a 2-level hierarchical model (centre and patient as the two levels). The model will include treatment study centre and any predefined covariates. Analysis will be by intention to treat. Project timetables including recruitment rate: The study will start June 1st 2011 for finalising ethics applications and R&D approvals recruitment of Trial Committee personnel development of Case Report Forms and training of trial personnel. Recruitment will start on 1st Sept 2011 and will recruit for 1 year. Laboratory analyses data cleaning analysis and reporting will take a further 9 months. All centres have audited adult asthma A & E attendances and have >300 per year. Some will be ineligible but we believe 38 per centre is achievable (rate required is 3.2 per centre per month).


Research activity codes: 5.1 PHARMACEUTICALS;6.1 PHARMACEUTICALS
Health categories: RESPIRATORY;INFECTION