Sebastian L Johnston1, Matyas Szigeti2, Mary Cross2, Christopher Brightling3, Rekha Chaudhuri4,5, Timothy Harrison6, Adel Mansur7,8, Laura Robison2, Zahid Sattar2, David Jackson1, Patrick Mallia1, Ernie Wong1, Christopher Corrigan9,10, Bernard Higgins11, Philip Ind1,12, Dave Singh13, Neil C Thomson4, Deborah Ashby2, Anoop Chauhan14. 1. National Heart and Lung Institute, Imperial College London, London, England. 2. Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, England. 3. Institute for Lung Health, University of Leicester, Leicester, England. 4. Institute of Infection Immunity and Inflammation, University of Glasgow, Glasgow, Scotland. 5. Respiratory Medicine, NHS Greater Glasgow and Clyde, Glasgow, Scotland. 6. Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, England. 7. Respiratory Medicine, Heart of England Foundation Trust, Birmingham, England. 8. Severe and Brittle Asthma Unit, University of Birmingham, Birmingham, England. 9. Respiratory Medicine and Allergy, King's College London School of Medicine, London, England. 10. Department of Asthma, Allergy and Respiratory Science, Guy's and St. Thomas' NHS Foundation Trust, London, England. 11. Respiratory Medicine, Newcastle University, Newcastle, England. 12. Respiratory Medicine, Imperial College Healthcare NHS Trust, London, England. 13. Centre for Respiratory Medicine and Allergy, Medicines Evaluation Unit, University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, England. 14. Respiratory Medicine, Portsmouth Hospitals NHS Trust, Portsmouth, England.
Abstract
Importance: Guidelines recommend against antibiotic use to treat asthma attacks. A study with telithromycin reported benefit, but adverse reactions limit its use. Objective: To determine whether azithromycin added to standard care for asthma attacks in adults results in clinical benefit. Design, Setting, and Participants: The Azithromycin Against Placebo in Exacerbations of Asthma (AZALEA) randomized, double-blind, placebo-controlled clinical trial, a United Kingdom-based multicenter study in adults requesting emergency care for acute asthma exacerbations, ran from September 2011 to April 2014. Adults with a history of asthma for more than 6 months were recruited within 48 hours of presentation to medical care with an acute deterioration in asthma control requiring a course of oral and/or systemic corticosteroids. Interventions: Azithromycin 500 mg daily or matched placebo for 3 days. Main Outcomes and Measures: The primary outcome was diary card symptom score 10 days after randomization, with a hypothesized treatment effect size of -0.3. Secondary outcomes were diary card symptom score, quality-of-life questionnaires, and lung function changes, all between exacerbation and day 10, and time to a 50% reduction in symptom score. Results: Of 4582 patients screened at 31 centers, 199 of a planned 380 were randomized within 48 hours of presentation. The major reason for nonrecruitment was receipt of antibiotics (2044 [44.6%] screened patients). Median time from presentation to drug administration was 22 hours (interquartile range, 14-28 hours). Exacerbation characteristics were well balanced across treatment arms and centers. The primary outcome asthma symptom scores were mean (SD), 4.14 (1.38) at exacerbation and 2.09 (1.71) at 10 days for the azithromycin group and 4.18 (1.48) and 2.20 (1.51) for the placebo group, respectively. Using multilevel modeling, there was no significant difference in symptom scores between azithromycin and placebo at day 10 (difference, -0.166; 95% CI, -0.670 to 0.337), nor on any day between exacerbation and day 10. No significant between-group differences were observed in quality-of-life questionnaires or lung function between exacerbation and day 10, or in time to 50% reduction in symptom score. Conclusions and Relevance: In this randomized population, azithromycin treatment resulted in no statistically or clinically significant benefit. For each patient randomized, more than 10 were excluded because they had already received antibiotics. Trial Registration: clinicaltrials.gov Identifier: NCT01444469.
RCT Entities:
Importance: Guidelines recommend against antibiotic use to treat asthma attacks. A study with telithromycin reported benefit, but adverse reactions limit its use. Objective: To determine whether azithromycin added to standard care for asthma attacks in adults results in clinical benefit. Design, Setting, and Participants: The Azithromycin Against Placebo in Exacerbations of Asthma (AZALEA) randomized, double-blind, placebo-controlled clinical trial, a United Kingdom-based multicenter study in adults requesting emergency care for acute asthma exacerbations, ran from September 2011 to April 2014. Adults with a history of asthma for more than 6 months were recruited within 48 hours of presentation to medical care with an acute deterioration in asthma control requiring a course of oral and/or systemic corticosteroids. Interventions: Azithromycin 500 mg daily or matched placebo for 3 days. Main Outcomes and Measures: The primary outcome was diary card symptom score 10 days after randomization, with a hypothesized treatment effect size of -0.3. Secondary outcomes were diary card symptom score, quality-of-life questionnaires, and lung function changes, all between exacerbation and day 10, and time to a 50% reduction in symptom score. Results: Of 4582 patients screened at 31 centers, 199 of a planned 380 were randomized within 48 hours of presentation. The major reason for nonrecruitment was receipt of antibiotics (2044 [44.6%] screened patients). Median time from presentation to drug administration was 22 hours (interquartile range, 14-28 hours). Exacerbation characteristics were well balanced across treatment arms and centers. The primary outcome asthma symptom scores were mean (SD), 4.14 (1.38) at exacerbation and 2.09 (1.71) at 10 days for the azithromycin group and 4.18 (1.48) and 2.20 (1.51) for the placebo group, respectively. Using multilevel modeling, there was no significant difference in symptom scores between azithromycin and placebo at day 10 (difference, -0.166; 95% CI, -0.670 to 0.337), nor on any day between exacerbation and day 10. No significant between-group differences were observed in quality-of-life questionnaires or lung function between exacerbation and day 10, or in time to 50% reduction in symptom score. Conclusions and Relevance: In this randomized population, azithromycin treatment resulted in no statistically or clinically significant benefit. For each patient randomized, more than 10 were excluded because they had already received antibiotics. Trial Registration: clinicaltrials.gov Identifier: NCT01444469.
Authors: Koen B Pouwels; F Christiaan K Dolk; David R M Smith; Julie V Robotham; Timo Smieszek Journal: J Antimicrob Chemother Date: 2018-02-01 Impact factor: 5.790
Authors: Malene Plejdrup Hansen; Anna M Scott; Amanda McCullough; Sarah Thorning; Jeffrey K Aronson; Elaine M Beller; Paul P Glasziou; Tammy C Hoffmann; Justin Clark; Chris B Del Mar Journal: Cochrane Database Syst Rev Date: 2019-01-18
Authors: Mihaela S Stefan; Meng-Shiou Shieh; Kerry A Spitzer; Penelope S Pekow; Jerry A Krishnan; David H Au; Peter K Lindenauer Journal: JAMA Intern Med Date: 2019-03-01 Impact factor: 21.873
Authors: Rebecca Normansell; Ben Sayer; Samuel Waterson; Emma J Dennett; Manuela Del Forno; Anne Dunleavy Journal: Cochrane Database Syst Rev Date: 2018-06-25