Bronchopulmonary Function in Response to Azithromycin Treatment for Chronic Lung Disease in HIV-infected Children
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 347
- 试验地点
- 2
- 主要终点
- Forced Expiratory Volume in one second z score (FEV1)
研究概览
简要总结
Chronic pulmonary disease (CLD) is the most common manifestation of HIV/AIDS among children, accounting for more than 50% of HIV-associated mortality. Recently, a novel form of CLD, affecting more than 30% of African HIV-infected older children was described by Ferrand et al in Zimbabwe, high-resolution CT scanning findings showed predominantly small airways disease consistent with constrictive obliterative bronchiolitis (OB). . Azithromycin has anti-inflammatory activity and treatment of CLD with this agent may lead to suppression of generalized immune activation.
This specific aims of this project are to:
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Primary objective: To investigate whether adjuvant treatment with azithromycin results in improvement in lung function in HIV-infected children with chronic lung disease, who are stable on antiretroviral therapy.
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Secondary objectives:
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To investigate the intervention effect on mortality, exacerbations of lung disease, quality of life, morbidity.
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To investigate adverse events related to azithromycin treatment
In total, 400 children aged 6-16 years, living with HIV and diagnosed with CLD will be enrolled at Harare Children´s Hospital in Harare (Zimbabwe) and Queen Elizabeth Central Hospital in Blantyre (Malawi). These will receive weekly treatment with azithromycin or placebo during 12 months. Another 100 children (50 per site) living with HIV but with no CLD will be enrolled as a comparison group for laboratory sub-studies.
Lung function will be assess using spirometry and the Forced expiratory volume in the first minute (FEV1) will be the primary outcome. The mean change in FEV1 z-score levels will be compared between trial arms after 12 months of initiation of azithromycin treatment.
详细描述
Clinical Phase: III
Trial Design: Multi-site, individually randomised, double-blinded, placebo-controlled trial of weekly azithromycin for 12 months
Trial Participants: Children aged 6-16 years living with HIV and with diagnosis of chronic lung disease. Another 200 children living with HIV but with no chronic lung disease in a comparison arm.
Planned Sample Size: 400 cases and 100 in the comparison arm
Treatment duration: 12 months
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of chronic lung disease (defined as FEV1 and/or FVC <80% predicted)
- •Age 6-19 years
- •Perinatally-acquired HIV infection the most likely source of transmission
- •On first or second-line ART for at least one year
- •HIV-1 viral load undetectable (as defined by each trial site)
- •A firm home address accessible for visiting and intending to remain there for 24 months
- •Willing to agree to participate in the study and to give samples of blood and sputum
- •HIV status disclosed to child for those aged older than 12 years
排除标准
- •Any condition (except HIV) that may prove fatal during the study period (e.g. malignancy, end-stage HIV disease or other conditions deemed likely fatal by the trial physician)
- •Diagnosis of active pulmonary TB
- •Infection with non-tuberculous mycobacteria (NTM)
- •Pregnant or breast-feeding
- •Condition likely to lead to lack of understanding of study procedures or to uncooperative behaviour e.g. neurocognitive disease, developmental delay or psychiatric illness
- •History of prolonged QTc syndrome or current or planned therapy with drugs likely to cause cardiac dysrhythmias
- •Abnormal ECG findings
- •Acute respiratory tract infection during enrolment (patients will be eligible once their acute infection is treated)
- •Creatinine clearance of <30mls/minute
- •ALT more than 2 times the upper limit of normal
- •No defined guardian/stable caregiver
- •No consent/assent from guardian/child
研究组 & 干预措施
Azithomycin
Azithromycin tablets 250 mg, 30mg/kg/week by mouth, once a week for 12 months.
- 10-20 kg: 250 mg
- 20-29 kg: 500 mg
- 30-39 kg: 750 mg
- 40-49 kg: 1250 mg
干预措施: Azithromycin (Drug)
Placebo
Placebo tablets 250 mg, 30 mg/kg/week by mouth, once a week for 12 months.
- 10-20 kg: 250 mg
- 20-29 kg: 500 mg
- 30-39 kg: 750 mg
- 40-49 kg: 1250 mg
干预措施: Placebo (Drug)
结局指标
主要结局
Forced Expiratory Volume in one second z score (FEV1)
时间窗: 12 months
Change in FEV1after 12 months of initiation of therapy with azithromycin
次要结局
- Number of gastroenteritis episodes(12 months)
- Time to first acute exacerbation(12 months)
- Mean change in weight-for-age z-score(12 and 24 months)
- Time to death(12 months)
- Number of exacerbations(12 and 24 months)
- Quality of life scores(12 and 24 months)
- Forced Expiratory Volume in one second z score (FEV1)(24 months)
- Number of blood stream infections due to Salmonella typhi and non-typhi(12 months)
- Number of hospitalizations(12 and 24 months)
- Number of Malaria episodes (Malawi only)(12 months)
- Number of mild, moderate and severe adverse events(12 months)