The Impact of Shigellosis and Recommended Treatment in Children
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 700
- 试验地点
- 4
- 主要终点
- Time to cessation of diarrhea (TCD)
研究概览
简要总结
The purpose of this study is to evaluate whether antibiotic treatment of non-dysentery Shigella associated watery diarrhea (NDSD) cases improves clinical outcomes and growth in children.
Children with NDSD seeking care for diarrhea at the study hospitals in Bangladesh and Zambia will be enrolled and randomized to receive Azithromycin or placebo (a look-alike substance that contains no drug). Enrolled children will be followed for three months with household visits.
The investigators will determine whether antibiotic treatment of NDSD reduces the duration of diarrhea and time to microbiological cure (shedding of Shigella in stool), and whether it improves growth in children compared with the placebo group.
详细描述
The current World Health Organization (WHO) guidelines for the treatment of diarrhea recommend antibiotics when visible blood is present in the stool and in cases suspected of cholera. Currently, >50% of Shigella-associated diarrhea cases are non-dysentery or watery diarrhea in nature; thus, would not be treated with antibiotics according to guidelines. Absence of dysentery does not exclude Shigella as a cause of diarrhea and may not indicate a lower risk of death. For particularly vulnerable younger or malnourished children, identification and treatment of Shigella infection might be lifesaving. Consequently, a critical question remains to be answered. Should cases of non-dysentery Shigella associated watery diarrhea (NDSD) be treated with antibiotics? The goal of this study is to determine whether antibiotic treatment of NDSD cases improves clinical outcomes and growth in children.
This is a phase 2B, randomized, double-blind, placebo-controlled study. Children aged >6-59 months with NDSD who are seeking care for diarrhea at the study hospitals in Bangladesh and Zambia will be enrolled and randomized to receive either Azithromycin or a placebo (a look-alike substance that contains no drug). All children will be rehydrated with either oral rehydration solution or intravenous fluids, depending on the degree of dehydration, and will receive zinc in accordance with standard of care. Enrolled children will be followed for three months through household visits to collect morbidity and anthropometry data.
Primary Outcomes
- Time to Cessation of Diarrhea (TCD) between intervention and placebo
- Change of Weight-for-age z-score (∆WAZ) in the 90 days following enrolment between intervention and placebo arms.
Secondary Outcomes
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
All participating parties with the exception of the study statistician will be masked.
入排标准
- 年龄范围
- 6 Months 至 59 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients >6 and ≤59 months of age seeking care in the study hospitals
- •Patients residing within the study catchment area
- •Present with watery diarrhea and positive for Shigella by RLDT
- •Willing to be available for sample and data collection during the follow up visits
排除标准
- •Inability or unwillingness of a participant's parent/guardian to give written informed consent or comply with study protocol
- •Diarrhea started more than 96 hours before enrollment
- •Antibiotics related to shigellosis treatment (including the investigational drug azithromycin) taken in the past 5 days
- •More than 2 doses of antidiarrheal drugs taken in the past 24 hours
- •History of allergy to Azithromycin
- •Presence of visible blood in stool
- •Children with severe acute malnutrition (below -3z scores of the median WHO growth standards).
- •History of congenital heart diseases, known gastrointestinal abnormalities, including short bowel syndrome, chronic (inflammatory or irritable) bowel disease, inherited or acquired immune system deficiency rendering the patient immunocompromised, including chronic/long-term steroid treatment or other immunosuppressive treatment
- •Fever over 39°C (102°F) with other complications that require antibiotic treatment
- •Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
研究组 & 干预措施
Azithromycin
Children 6-59 months with non-dysentery shigella diarrhea will be treated with Azithromycin 10 mg/kg once daily for 5 days.
干预措施: Azithromycin (Drug)
Placebo
Children 6-59 months with non-dysentery Shigella diarrhea will receive placebo similar in appearance to the experimental drug once daily for 5 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Time to cessation of diarrhea (TCD)
时间窗: From the time of the administration of Azithromycin or placebo until cessation of the diarrhea episode (approximately up to a month)
Diarrhea will be defined as 3 or more liquid or loose stool during a 24 hours period (not calendar day). Two diarrhea episodes will be separated by three diarrhea free days in between. Time to cessation of diarrhea (TCD) will be expressed in hours.
Change in weight for age Z score (WAZ)
时间窗: From enrollment to the 90-day follow up
The change in weight for age Z scores from enrollment to the 90-day follow-up
次要结局
- Time to microbiological cure(Enrollment to microbiological cure (up to 3 months))
- Change in length for age Z score (LAZ)(From enrollment to 90-day follow-up.)