Antibiotics for Children With Severe Diarrhoea
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 8,268
- 试验地点
- 7
- 主要终点
- Mortality
研究概览
简要总结
Although the current World Health Organization (WHO) recommended management package for acute diarrhoea (ORS, zinc and feeding advice) has contributed to significant reductions in diarrhoea associated mortality, over half a million children continue to die annually as a result of acute diarrhoeal episodes. In addition, rates of mortality in young children in the 90 days following an episode of acute diarrhoea appear at least as high as mortality that occurs during the acute episode. The long-term benefits of antibiotic administration may result from direct antimicrobial effects on pathogens or from other incompletely understood mechanisms including improved nutrition, alterations in immune tolerance or improved enteric function. Optimizing antibiotic treatment of acute diarrhoea episodes in very young children with severe disease may offer the opportunity to significantly reduce diarrhoea associated deaths in the 180 days following presentation for acute diarrhoea and may also improve growth.
The investigators propose to evaluate the efficacy of an antibiotic (azithromycin) delivered in a specific, targeted fashion to young children (< 2 years of age) at high risk of diarrhoea associated mortality in a multi-site randomized, double-blind, placebo-controlled trial. The study will evaluate the ability of the intervention to reduce mortality within 180 days of the acute diarrhoeal episode, and improve nutritional status over the first 90 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Active drug (azithromycin) will be delivered as dry powder, in opaque glass bottles. Control children with receive placebo powder that will appear, smell, and taste similar to the active drug. All drug bottles will be coded with participant numbers only, so that no-one will know the contents of the bottle.
入排标准
- 年龄范围
- 2 Months 至 23 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children aged 2 - 23 months, presenting to a designated health care facility at a participating study site with
- •Diarrhoea per caregiver perception and at least 3 loose or watery stools in the previous 24 hours,
- •Diarrhoea for less than 14 days prior to screening and with at least one of the following criteria at presentation:
- •Signs of some or severe dehydration as per WHO Pocket Book 2013
- •Moderately wasted as defined by a mid-upper arm circumference (MUAC) less than 125 mm (but greater than or equal to 115 mm) or a weight-for-length z-score (WLZ) greater than -3 standard deviations (SD) and less than or equal to -2 SD after rehydration during stabilization period or
- •Severely stunted (length-for-age z-score (LAZ) <-3 SD) and
- •Parent or guardian (caregiver) willing to allow household visits on day 2 and day 3 and willing to return to facility on day 90 and
- •Parent or guardian (caregiver) provides a consent for trial participation on behalf of the child, based on local standards
排除标准
- •Dysentery (gross blood in stool reported by caregiver or observed by healthcare worker (HCW)),
- •Suspected Vibrio cholerae infection (determined according to WHO guidelines or clinical suspicion),
- •Previously or currently enrolled in the ABCD study,
- •Concurrently enrolled in another interventional clinical trial,
- •Sibling or other child in the household enrolled in the ABCD study and currently taking study medication,
- •Signs of associated infections (pneumonia, severe febrile illness, meningitis, mastoiditis or acute ear infection) requiring antibiotic treatment,
- •Documented antibiotic use in the 14 days prior to screening (not including standard use of prophylactic antibiotics, i.e. co-trimoxazole use in human immunodeficiency virus (HIV) -exposed children),
- •Documented use of metronidazole within the last 14-days,
- •Known allergy or contraindication to azithromycin antibiotics,
- •Severe acute malnutrition (SAM) defined as weigh-for-length Z-score (WLZ) less than -3 SD, or MUAC less than 115 mm, or edema of both feet, or
- •Living too far from the enrolment health center to ensure adequate Directly Observed Therapy (DOT) on day 2 and day 3
研究组 & 干预措施
Control
Placebo mixture, 0.25 ml / kg / day
干预措施: Placebo (Other)
Azithromycin
Azithromycin mixture (40 mg / ml), 0.25 ml / kg / day
干预措施: Azithromycin (Drug)
结局指标
主要结局
Mortality
时间窗: 180 days from enrolment
Proportion of children dying per arm
Linear growth
时间窗: 90 days from enrolment
Mean change in length-for-age Z-score per arm. The Z score will be arrived at from the WHO growth charts based on length in cms and age in months
次要结局
- Change in weight for age Z score(90 days)
- Change in Mid upper arm circumference(90 days)
- Antimicrobial resistance in the community(Baseline)
- Antimicrobial resistance among the study participants (sub-group)(At the end of intervention (90 days) and three months later (180 days))
- Hospitalizations upto Day 90(90 days)
- Hospitalization or deaths upto day 90(90 days)
- Early hospitalization or death (upto day 10)(10 days)
- Change in weight for length Z score(90 days)
- Antimicrobial resistance among close household child contacts (sub-group)(At the end of intervention (90 days) and three months later (180 days))
研究者
Ayesha De Costa
Scientist
World Health Organization