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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dc.contributor.author Gonzalez-Martinez, Carmen
dc.contributor.author Kranzer, Katharina
dc.contributor.author McHugh, Grace
dc.contributor.author Corbett, Elizabeth L
dc.contributor.author Mujuru, Hilda
dc.contributor.author Nicol, Mark P
dc.contributor.author Rowland-Jones, Sarah
dc.contributor.author Rehman, Andrea M
dc.contributor.author Gutteberg, Tore J
dc.contributor.author Flaegstad, Trond
dc.contributor.author Odland, Jon O
dc.contributor.author Ferrand, Rashida A
dc.date.accessioned 2018-01-09T07:50:42Z
dc.date.available 2018-01-09T07:50:42Z
dc.date.issued 2017-12-28
dc.identifier.citation Gonzalez-Martinez, C., Kranzer, K., McHugh, G., Corbett, E. L., Mujuru, H., Nicol, M. P., ... & Odland, J. O. (2017). 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. Trials, 18(1), 622.
dc.identifier.uri http://dx.doi.org/10.1186/s13063-017-2344-2
dc.identifier.uri http://hdl.handle.net/11427/26750
dc.description.abstract Background: Human 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/design: We 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. Discussion: The 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 HIVinfected children live and where HIV-associated CLD is highly prevalent. Trial registration: ClinicalTrials.gov, NCT02426112. Registered on 21 April 2015.
dc.language.iso en
dc.publisher BioMed Central
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.source Trials
dc.source.uri https://trialsjournal.biomedcentral.com/
dc.subject.other Chronic lung disease
dc.subject.other Azithromycin
dc.subject.other HIV
dc.subject.other FEV1
dc.subject.other Africa
dc.subject.other Children
dc.subject.other Obliterative bronchiolitis
dc.title 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
dc.type Journal Article
dc.date.updated 2017-12-31T04:17:14Z
dc.rights.holder The Author(s).
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Department of Medicine en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Gonzalez-Martinez, C., Kranzer, K., McHugh, G., Corbett, E. L., Mujuru, H., Nicol, M. P., ... Ferrand, R. A. (2017). 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. <i>Trials</i>, http://hdl.handle.net/11427/26750 en_ZA
dc.identifier.chicagocitation Gonzalez-Martinez, Carmen, Katharina Kranzer, Grace McHugh, Elizabeth L Corbett, Hilda Mujuru, Mark P Nicol, Sarah Rowland-Jones, et al "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." <i>Trials</i> (2017) http://hdl.handle.net/11427/26750 en_ZA
dc.identifier.vancouvercitation Gonzalez-Martinez C, Kranzer K, McHugh G, Corbett EL, Mujuru H, Nicol MP, et al. 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. Trials. 2017; http://hdl.handle.net/11427/26750. en_ZA
dc.identifier.ris TY - Journal Article AU - Gonzalez-Martinez, Carmen AU - Kranzer, Katharina AU - McHugh, Grace AU - Corbett, Elizabeth L AU - Mujuru, Hilda AU - Nicol, Mark P AU - Rowland-Jones, Sarah AU - Rehman, Andrea M AU - Gutteberg, Tore J AU - Flaegstad, Trond AU - Odland, Jon O AU - Ferrand, Rashida A AB - Background: Human 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/design: We 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. Discussion: The 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 HIVinfected children live and where HIV-associated CLD is highly prevalent. Trial registration: ClinicalTrials.gov, NCT02426112. Registered on 21 April 2015. DA - 2017-12-28 DB - OpenUCT DO - 10.1186/s13063-017-2344-2 DP - University of Cape Town J1 - Trials LK - https://open.uct.ac.za PB - University of Cape Town PY - 2017 T1 - 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 TI - 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 UR - http://hdl.handle.net/11427/26750 ER - en_ZA


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