Gonzalez-Martinez Carmen, Kranzer Katharina, McHugh Grace, Corbett Elizabeth L, Mujuru Hilda, Nicol Mark P, Rowland-Jones Sarah, Rehman Andrea M, Gutteberg Tore J, Flaegstad Trond, Odland Jon O, Ferrand Rashida A
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Malawi-Liverpool Wellcome Trust Clinical Research Programme, PO Box 30096, Chichiri, Blantyre 3, Malawi.
Trials. 2017 Dec 28;18(1):622. doi: 10.1186/s13063-017-2344-2.
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 (FEV) z-score at 12 months. Participants are followed up to 18 months to explore the durability of effect. Secondary outcomes are FEV 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.
尽管接受了抗逆转录病毒治疗，但儿童中与人类免疫缺陷病毒（HIV）相关的慢性肺病（CLD）仍与相当高的发病率相关。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。大环内酯类药物具有抗炎和抗菌特性，我们推测阿奇霉素可通过预防呼吸道感染和控制全身炎症来减少肺功能下降和发病率。
方法/设计：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，比较为期12个月的每周一次阿奇霉素疗程与安慰剂。主要结局是12个月时1秒用力呼气量（FEV）z评分的平均变化。对参与者随访18个月以探究效果的持续性。次要结局包括18个月时的FEV z评分、死亡时间、首次急性呼吸道加重时间、加重次数、住院次数、12个月和18个月时的年龄别体重z评分、不良事件数量、疟疾发作次数、血流伤寒沙门氏菌感染次数和肠胃炎发作次数。将每3个月对参与者进行一次随访，每6个月评估一次肺功能。将开展实验室子研究以调查阿奇霉素对全身炎症、抗菌药物耐药性发展的影响以及对鼻咽、肺和肠道微生物群的影响。
该试验结果将具有临床相关性，因为在撒哈拉以南非洲地区，尚无关于儿童HIV相关CLD治疗和管理的既定指南，而全球80%感染HIV的儿童生活在该地区，且HIV相关CLD非常普遍。
ClinicalTrials.gov，NCT02426112。于2015年4月21日注册。
