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

and the BREATHE study team

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Article number622
JournalTrials
Volume18
Issue number1
DOIs
Publication statusPublished - 28 Dec 2017
Externally publishedYes

Fingerprint

Azithromycin
Clinical Protocols
Lung Diseases
Chronic Disease
Randomized Controlled Trials
Placebos
HIV
Forced Expiratory Volume
Respiratory Tract Infections
Lung
Inflammation
Morbidity
Therapeutics
Malawi
Zimbabwe
Salmonella typhi
Salmonella Infections
Africa South of the Sahara
Macrolides
Gastroenteritis

Cite this

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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",
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.",
keywords = "Africa, Azithromycin, Children, Chronic lung disease, FEV, HIV, Obliterative bronchiolitis",
author = "{and the BREATHE study team} and Carmen Gonzalez-Martinez and Katharina Kranzer and Grace McHugh and Corbett, {Elizabeth L.} and Hilda Mujuru and Nicol, {Mark P.} and Sarah Rowland-Jones and Rehman, {Andrea M.} and Gutteberg, {Tore J.} and Trond Flaegstad and Odland, {Jon O.} and Ferrand, {Rashida A.} and Tsitsi Bandason and Pauline Cavanagh and Ethel Dauya and Edith Majonga and Beauty Makamure and Mapurisa, {Gugulethu Newton} and Slee Mbhele and Moyo, {Brewster Wisdom} and Ngwira, {Lucky Gift} and Jamie Rylance and Victoria Simms and Evgeniya Sovershaeva and Weiss, {Helen Anne} and Yindom, {Louis Marie}",
year = "2017",
month = "12",
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doi = "10.1186/s13063-017-2344-2",
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journal = "Trials",
issn = "1745-6215",
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TY - JOUR

T1 - Azithromycin versus placebo for the treatment of HIV-associated chronic lung disease in children and adolescents (BREATHE trial)

T2 - Study protocol for a randomised controlled trial

AU - and the BREATHE study team

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

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 - 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.

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 HIV-infected children live and where HIV-associated CLD is highly prevalent. Trial registration: 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

UR - http://www.scopus.com/inward/record.url?scp=85039547779&partnerID=8YFLogxK

U2 - 10.1186/s13063-017-2344-2

DO - 10.1186/s13063-017-2344-2

M3 - Article

VL - 18

JO - Trials

JF - Trials

SN - 1745-6215

IS - 1

M1 - 622

ER -