Antibiotics for Children with Severe Diarrhoea (ABCD) Trial
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 11,500
- 试验地点
- 1
- 主要终点
- -Mortality
研究概览
简要总结
The study is a double-blind, placebo controlled, randomized trial aims to evaluate the efficacy of antibiotic (azithromycin), compared to placebo, in reducing risk of death and linear growth faltering in the three months following an episode of diarrhea among children (2-23 months of age) at high-risk of diarrhea-associated mortality. In this trial, 11,500 children aged 2 to 23 months presenting to health facilities/hospitals in 7 Asian (Bangladesh, India and Pakistan) and Sub-Saharan African countries with acute diarrhea and either malnutrition or dehydration will be enrolled and followed up for 90 days (a subgroup will be followed up for 180 days). Children will be randomized to receive a three-day course of azithromycin, or placebo. In India, the study willbe conducted in two tertiary care hospitals [1 private - Subharti Medical College (SMC) and 1 government - Lala Lajpat Rai Memorial (LLRM) Medical College], and 1 district hospital of the Meerut District, Uttar Pradesh and in selected CHCs/PHCs.
Surveillance system will be set up at the selected health facilities to identify children with diarrhoea. Children aged 2-23 months with diarrhea will undergo the screening process. At the time of screening, information on diarrhea, dehydration, danger signs, vital status, child’s medical history, family background will be taken and detailed physical examination will be conducted. Anthropometric measurements (weight, length, mid-upper arm circumference- MUAC) will also be taken and recorded. If the child meets the eligibility criteria, informed written consent will be obtained and the child gets enrolled. Enrolled children will be randomized to receive one of the two treatment regimes for three days under direct supervision and observation (DOT). At baseline, information on socio-demographics and child’s vaccination history will be obtained. In addition stool samples will be collected.
Children will be re-assessed at 3-months to determine the vital status of the child and to obtain anthropometric measurements. If at any of the follow-up visits, a caregiver reports that a child has died, a verbal autopsy interview will be conducted.
A sub-set of children (n- ~230) will also be followed for 6-months for additional sample collection for antimicrobial resistance (AMR) sub-study. Stool samples and nasopharyngeal swabs will be collected from enrolled children and child contact (6 months to 59 months of age) of the enrolled child at 3 months and 6 months.
The primary outcome measures will be all-cause mortality and linear growth faltering at 3 months. The secondary outcomes will be cause-specific mortality, acute malnutrition (∆MUAC and WHZ), individual and community-level antimicrobial resistance in bacterial enteric and nasopharyngeal infections at 3 months and 6 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Permuted block randomization, variable
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 2.00 Month(s) 至 23.00 Month(s)（—）
- 性别
- All
入选标准
- •1.Children aged 2 – 23 months, presenting to a designated health care facility at a participating study site WITH 2.Diarrhoea per caregiver perception AND at least 3 unusually loose or watery stools in the previous 24 hours, 3.Diarrhoea for less than 14 days prior to screening AND with at least one of the following criteria at presentation: 3.1.Signs of some or severe dehydration as per WHO pocket Book 2013 3.2.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 -3SD and less than or equal to -2SD after rehydration during stabilization period or 3.3.Severely stunted (Length-for-age z-score (LAZ) <-3 SD) AND 4.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 5.Parent or guardian (caregiver) provides a consent for trial participation on behalf of the child.
排除标准
- •1.Dysentery (gross blood in stool reported by parent or observed by HCW) 2.Suspected Vibrio Cholerae infection (determined according to WHO guidelines or clinical suspicion) 3.Previously or currently enrolled in the ABCD study 4.Concurrently enrolled in another interventional clinical trial 5.Sibling or other child in the household enrolled in the ABCD study and currently taking study medication 6.Signs of associated infections (pneumonia, severe febrile illness, meningitis, mastoiditis or acute ear infection)requiring alternate antibiotic treatment 7.Documented antibiotic use in the 14 days prior to screening (not including standard use of prophylactic antibiotics, i.e. co-trimoxazole use in HIV-exposed children) 8.Documented use of metronidazole within the last 14 days 9.Known allergy or contraindication to azithromycin antibiotics 10.Severe acute malnutrition(SAM)defined as weight-for-length z-score less than −3 SD, or MUAC less than 115 mm or edema of both feet,OR 11.Living too far from the enrolment health center to ensure adequate Directly Observed Therapy(DOT)on DAY 2 and DAY 3.
结局指标
主要结局
-Mortality
时间窗: From enrolment till Day-90 of follow-up (if the participant misses day-90 visit, mortality data can be collected until day-180
-Hospitalizations(number and categorized causes)
时间窗: From enrolment till Day-90 of follow-up (if the participant misses day-90 visit, mortality data can be collected until day-180
-Assessment of linear growth (∆length-for-age z-score):
时间窗: From enrolment till Day-90 of follow-up (if the participant misses day-90 visit, mortality data can be collected until day-180
次要结局
- -Assessment of acute malnutrition (∆MUAC and WHZ)(-Assessment of cause specific mortality (determined by verbal autopsy))