Trial of Zinc Supplements for Young Infants with Clinical Severe Infection in Tanzania

在坦桑尼亚对患有临床严重感染的小婴儿进行锌补充剂试验

• 批准号: 10635077
• 负责人: CHRISTOPHER P DUGGAN
• 金额: $ 64.85万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-17 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10635077
• 关键词: Africa South of the Sahara; Age; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Asia; Bacterial Infections; Biological; Case Fatality Rates; Cessation of life; Chest; Child; Child Mortality; Childhood; Clinical; Clinical Management; Data; Developing Countries; Development; Enrollment; Etiology; Exposure to; Genetic; Goals; Growth; Guidelines; Health; Heterogeneity; Hospitalization; Hospitals; Incidence; Infant; Infant Health; Infant Mortality; Infection; Innovative Therapy; Intervention; Length; Life; Magnesium; Meningitis; Meta-Analysis; Modification; Morbidity - disease rate; Movement; Northern Africa; Nutrient availability; Nutritional status; Oral; Outcome; Participant; Placebos; Pneumonia; Policies; Population; Probability; Publishing; Randomized; Randomized, Controlled Trials; Recommendation; Regimen; Reporting; Risk; Sample Size; Sepsis; Severities; Signs and Symptoms; Specimen; Sustainable Development; Tablets; Tanzania; Temperature; Time; Treatment Failure; Treatment outcome; Variant; Vital Status; Weight; World Health Organization; Zinc Sulfate; Zinc deficiency; Zinc supplementation; cost; disability; double-blind placebo controlled trial; efficacy testing; hospital readmission; improved; innovation; low and middle-income countries; mortality; neonatal death; neonate; primary outcome; randomized trial; secondary outcome; success; survival outcome; treatment effect

Project Summary The overall project goal is to investigate zinc supplementation in combination with standard antibiotic therapy as a simple, low-cost, and readily available intervention to improve survival and treatment outcomes for Tanzanian young infants hospitalized with ‘clinical severe infection’ as defined by WHO IMCI criteria. To meet these goals, we propose to conduct a ‘gold standard’ randomized, double-blind, placebo-controlled trial of zinc supplementation in Dar es Salaam, Tanzania. Briefly, we will enroll 3,250 Tanzanian young infants (0-59 days) hospitalized with clinical severe infection in Dar es Salaam, Tanzania. All young infants will receive standard antibiotic treatment and will be randomized to receive a 14-day course of twice-daily oral 5 mg elemental zinc supplements (10 mg per day) or a matching 14- day course of a twice-daily placebo regimen. Participants will be followed-up for 90 days to assess vital status and treatment outcomes. We will also collect biological specimens to evaluate potential mechanisms of action and assess modification of any treatment effect by etiology of infection. The primary outcomes of the trial are i) 90-day all-cause mortality and ii) Treatment failure (composite endpoint of death, a new requirement for life support or need to change to second-line antibiotics). The secondary outcomes of the trial include a) time to cessation of signs and symptoms of clinical severe infection, b) time to hospital discharge, c) risk of re- hospitalization and d) 90-day change in nutritional status as assessed by length-for-age, weight-for-length, and weight-for-age z-scores. Evidence from this randomized trial is urgently needed as low-cost and high-impact innovation to improve young infant survival will be required for Tanzania and other developing countries to reach the child mortality Sustainable Development Goal (SDG) by 2030.

项目摘要 项目的总体目标是研究锌补充剂与标准抗生素治疗的结合 作为一种简单，低成本，易于获得的干预措施，以改善生存和治疗结果 坦桑尼亚年幼婴儿因WHO IMCI标准定义的“临床严重感染”住院。满足 为了实现这些目标，我们建议对锌进行一项“金标准”随机、双盲、安慰剂对照试验 坦桑尼亚达累斯萨拉姆的一项研究。 简而言之，我们将招募3，250名因临床严重感染住院的坦桑尼亚幼儿（0-59天）， 坦桑尼亚达累斯萨拉姆所有年幼的婴儿将接受标准抗生素治疗，并将被随机分配至 接受为期14天的疗程，每天两次口服5毫克元素锌补充剂（每天10毫克）或匹配的14- 每天两次的安慰剂方案的日疗程。参与者将接受90天的随访，以评估生命状态 和治疗结果。我们还将收集生物标本以评估潜在的作用机制 并通过感染病因学评估任何治疗效果的改变。试验的主要结果是 i）90天全因死亡率和ii）治疗失败（死亡复合终点，对生命的新要求 支持或需要改用二线抗生素）。试验的次要结局包括：a） 临床严重感染的体征和症状停止，B）出院时间，c）再感染风险 住院和d）90天营养状况变化，通过年龄别身高、身长别体重和 年龄别体重Z值 这项随机试验的证据是迫切需要的低成本和高影响力的创新，以改善 坦桑尼亚和其他发展中国家要达到儿童死亡率， 2030年可持续发展目标（SDG）。