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
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...
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| Format: | Article |
| Language: | English |
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BMC
2017-12-01
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| Series: | Trials |
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| Online Access: | http://link.springer.com/article/10.1186/s13063-017-2344-2 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Carmen Gonzalez-Martinez |
| collection | DOAJ |
| 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 HIV-infected children live and where HIV-associated CLD is highly prevalent. Trial registration ClinicalTrials.gov, NCT02426112 . Registered on 21 April 2015. |
| first_indexed | 2024-12-18T08:31:37Z |
| format | Article |
| id | doaj.art-0309791b7b764f4296baf1b76516ff78 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-18T08:31:37Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-0309791b7b764f4296baf1b76516ff782022-12-21T21:14:26ZengBMCTrials1745-62152017-12-011811810.1186/s13063-017-2344-2Azithromycin versus placebo for the treatment of HIV-associated chronic lung disease in children and adolescents (BREATHE trial): study protocol for a randomised controlled trialCarmen Gonzalez-Martinez0Katharina Kranzer1Grace McHugh2Elizabeth L. Corbett3Hilda Mujuru4Mark P. Nicol5Sarah Rowland-Jones6Andrea M. Rehman7Tore J. Gutteberg8Trond Flaegstad9Jon O. Odland10Rashida A. Ferrand11the BREATHE study teamLiverpool School of Tropical MedicineDepartment of Clinical Research, London School of Hygiene and Tropical MedicineBiomedical Research and Training InstituteMalawi-Liverpool Wellcome Trust Clinical Research ProgrammeDepartment of Paediatrics, University of ZimbabweDivision of Clinical Microbiology, University of Cape TownNuffield Department of Medicine, Old Road Campus, University of OxfordMRC Tropical Epidemiology Group, London School of Hygiene and Tropical MedicineDepartment of Microbiology and Infection Control, University Hospital of North NorwayFaculty of Health Sciences, Arctic University of NorwayFaculty of Health Sciences, Arctic University of NorwayBiomedical Research and Training InstituteAbstract 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 HIV-infected children live and where HIV-associated CLD is highly prevalent. Trial registration ClinicalTrials.gov, NCT02426112 . Registered on 21 April 2015.http://link.springer.com/article/10.1186/s13063-017-2344-2Chronic lung diseaseAzithromycinHIVFEV1AfricaChildren |
| spellingShingle | 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 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 Chronic lung disease Azithromycin HIV FEV1 Africa Children |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Chronic lung disease Azithromycin HIV FEV1 Africa Children |
| url | http://link.springer.com/article/10.1186/s13063-017-2344-2 |
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