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.contributor.authorGonzalez-Martinez, Carmen
dc.contributor.authorKranzer, Katharina
dc.contributor.authorMcHugh, Grace
dc.contributor.authorCorbett, Elizabeth L
dc.contributor.authorMujuru, Hilda
dc.contributor.authorNicol, Mark P
dc.contributor.authorRowland-Jones, Sarah
dc.contributor.authorRehman, Andrea M
dc.contributor.authorGutteberg, Tore J
dc.contributor.authorFlaegstad, Trond
dc.contributor.authorOdland, Jon O
dc.contributor.authorFerrand, Rashida A
dc.date.accessioned2018-01-09T07:50:42Z
dc.date.available2018-01-09T07:50:42Z
dc.date.issued2017-12-28
dc.date.updated2017-12-31T04:17:14Z
dc.description.abstractBackground: 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.identifier.apacitationGonzalez-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/11427/26750en_ZA
dc.identifier.chicagocitationGonzalez-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/11427/26750en_ZA
dc.identifier.citationGonzalez-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.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
dc.identifier.urihttp://dx.doi.org/10.1186/s13063-017-2344-2
dc.identifier.urihttp://hdl.handle.net/11427/26750
dc.identifier.vancouvercitationGonzalez-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.language.isoen
dc.publisherBioMed Central
dc.publisher.departmentDepartment of Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rights.holderThe Author(s).
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceTrials
dc.source.urihttps://trialsjournal.biomedcentral.com/
dc.subject.otherChronic lung disease
dc.subject.otherAzithromycin
dc.subject.otherHIV
dc.subject.otherFEV1
dc.subject.otherAfrica
dc.subject.otherChildren
dc.subject.otherObliterative bronchiolitis
dc.titleAzithromycin 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.typeJournal Article
uct.type.filetypeText
uct.type.filetypeImage
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