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
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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DOI：
10.1186/s13063-017-2344-2
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发表时间：
2017-12-28
期刊：
影响因子：
2.5
通讯作者：
Ferrand, Rashida A.
中科院分区：
文献类型：
--
作者：
Gonzalez-Martinez, Carmen;Kranzer, Katharina;Ferrand, Rashida A.
背景资料：儿童中与人类免疫缺陷病毒（HIV）相关的慢性肺病（CLD）与大量发病率相关，尽管进行了抗逆转录病毒治疗。这可能是反复呼吸道感染和/或伴随HIV感染的免疫激活失调的结果。大环内酯类具有抗炎和抗菌特性，我们假设阿奇霉素将减少肺功能和发病率下降，通过预防呼吸道感染和控制全身inflammation.Methods/Design：我们正在进行一项多中心（马拉维和津巴布韦），双盲，随机对照试验，为期12个月的每周阿奇霉素与安慰剂。主要结局是12个月时1秒用力呼气量（FEV 1）z评分的平均变化。参与者被随访长达18个月，以探索效果的持久性。次要结局是18个月时的FEV 1 z评分、至死亡时间、至首次急性呼吸道加重的时间、加重次数、住院次数、12和18个月时的年龄别体重z评分、不良事件次数、疟疾发作次数、血流伤寒沙门氏菌感染次数和胃肠炎发作次数。受试者将接受3个月随访，每6个月评估一次肺功能。将进行实验室亚组研究，以研究阿奇霉素对全身性炎症和抗菌素耐药性发展的影响，以及对鼻咽、肺和肠道微生物组的影响。这项试验的结果将具有临床意义，因为在撒哈拉以南非洲地区，世界上80%的艾滋病毒感染儿童生活在那里，艾滋病毒相关的慢性肝病非常普遍。
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.