TY - JOUR
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.
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.
AU - Bandason, Tsitsi
AU - Cavanagh, Pauline
AU - Dauya, Ethel
AU - Majonga, Edith
AU - Makamure, Beauty
AU - Mapurisa, Gugulethu Newton
AU - Mbhele, Slee
AU - Moyo, Brewster Wisdom
AU - Ngwira, Lucky Gift Chiwiya
AU - Rylance, Jamie
AU - Simms, Victoria
AU - Sovershaeva, Evgeniya
AU - Weiss, Helen Anne
AU - Yindom, Louis Marie
PY - 2017/12/28
Y1 - 2017/12/28
N2 - 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. 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. 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. ClinicalTrials.gov, NCT02426112 . Registered on 21 April 2015.
AB - 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. 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. 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. ClinicalTrials.gov, NCT02426112 . Registered on 21 April 2015.
KW - Africa
KW - Azithromycin
KW - Children
KW - Chronic lung disease
KW - FEV
KW - HIV
KW - Obliterative bronchiolitis
U2 - 10.1186/s13063-017-2344-2
DO - 10.1186/s13063-017-2344-2
M3 - Article
SN - 1745-6215
VL - 18
SP - 622
JO - Trials
JF - Trials
IS - 1
M1 - 622
ER -
