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

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，我们建议进行一项锌的“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）。

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.