Azithromycin versus placebo for the treatment of HIV-associated chronic lung disease in children and adolescents (BREATHE trial): study protocol for a randomised controlled trial |
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| Authors: | Carmen Gonzalez-Martinez Katharina Kranzer Grace McHugh Elizabeth L Corbett Hilda Mujuru Mark P Nicol Sarah Rowland-Jones Andrea M Rehman Tore J Gutteberg Trond Flaegstad Jon O Odland Rashida A Ferrand the BREATHE study team |
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| Institution: | 1.Liverpool School of Tropical Medicine,Liverpool,UK;2.Malawi-Liverpool Wellcome Trust Clinical Research Programme,Blantyre 3,Malawi;3.Department of Paediatrics and Child Health,College of Medicine, University of Malawi,Blantyre 3,Malawi;4.Department of Clinical Research,London School of Hygiene and Tropical Medicine,London,UK;5.Biomedical Research and Training Institute,Harare,Zimbabwe;6.Department of Infectious Disease Epidemiology,London School of Hygiene and Tropical Medicine,London,UK;7.Department of Paediatrics,University of Zimbabwe,Harare,Zimbabwe;8.Division of Clinical Microbiology,University of Cape Town,Cape Town,South Africa;9.National Health Laboratory Service,Johannesburg,South Africa;10.Nuffield Department of Medicine,Old Road Campus, University of Oxford,Oxford,UK;11.MRC Tropical Epidemiology Group,London School of Hygiene and Tropical Medicine,London,UK;12.Department of Microbiology and Infection Control,University Hospital of North Norway,Troms?,Norway;13.Faculty of Health Sciences,Arctic University of Norway,Troms?,Norway;14.Department of Paediatrics,University Hospital of North Norway,Troms?,Norway;15.School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria,Hatfield,South Africa |
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| Abstract: | BackgroundHuman immunodeficiency virus (HIV)-related chronic lung disease (CLD) among children is associated with substantial morbidity, despite antiretroviral therapy. This may be a consequence of repeated respiratory tract infections and/or dysregulated immune activation that accompanies HIV infection. Macrolides have anti-inflammatory and antimicrobial properties, and we hypothesised that azithromycin would reduce decline in lung function and morbidity through preventing respiratory tract infections and controlling systemic inflammation.Methods/designWe are conducting a multicentre (Malawi and Zimbabwe), double-blind, randomised controlled trial of a 12-month course of weekly azithromycin versus placebo. The primary outcome is the mean change in forced expiratory volume in 1 second (FEV1) z-score at 12 months. Participants are followed up to 18 months to explore the durability of effect. Secondary outcomes are FEV1 z-score at 18 months, time to death, time to first acute respiratory exacerbation, number of exacerbations, number of hospitalisations, weight for age z-score at 12 and 18 months, number of adverse events, number of malaria episodes, number of bloodstream Salmonella typhi infections and number of gastroenteritis episodes. Participants will be followed up 3-monthly, and lung function will be assessed every 6 months. Laboratory substudies will be done to investigate the impact of azithromycin on systemic inflammation and on development of antimicrobial resistance as well as impact on the nasopharyngeal, lung and gut microbiome.DiscussionThe results of this trial will be of clinical relevance because there are no established guidelines on the treatment and management of HIV-associated CLD in children in sub-Saharan Africa, where 80% of the world’s HIV-infected children live and where HIV-associated CLD is highly prevalent.Trial registrationClinicalTrials.gov, NCT02426112. Registered on 21 April 2015. |
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