A randomized clinical trial of early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa
撒哈拉以南非洲地区早期经验性抗结核杆菌治疗败血症的随机临床试验
基本信息
- 批准号:10265511
- 负责人:
- 金额:$ 66.28万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-18 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
PROJECT SUMMARY/ABSTRACT
Sepsis is a syndrome of critical illness defined as life-threatening organ dysfunction due to a dysregulated host
response to infection and is a leading cause of global mortality. In May of 2017, the World Health
Organization (WHO) made sepsis a global health priority. Yet, little is known about sepsis in the global
South and specifically sub-Saharan Africa where there are at least 1.2-2.2 million cases of sepsis and 6.5
million deaths due to infection annually. The majority of these patients are living with HIV. We have determined
the leading cause of sepsis in this region is tuberculosis (TB) which is responsible for 25-30% of bloodstream
infections in septic patients. TB sepsis is associated with 20-50% mortality rates with the majority of deaths
occurring within the first 4-5 days of admission. However, it is difficult to identify TB sepsis clinically or with
diagnostic tests which are often unavailable and have limited sensitivity. Therefore, TB can be missed and
patients with TB sepsis may not receive anti-TB therapy, or if they do, it may be delayed. However, we have
found that empiric treatment of TB in septic patients without a confirmed diagnosis of TB improves 28 day
survival. We have also studied anti-TB pharmacokinetics/pharmacodynamics in septic patients and discovered
considerably low circulating drug concentrations that are suboptimal for microbial kill. Therefore, our
hypotheses are that immediate anti-TB therapy will improve 28 day survival compared to anti-TB therapy that
is administered only after a diagnosis is made, and that optimized sepsis-specific dosing will improve 28 day
mortality compared to conventional WHO recommended weight-based dosing regardless of the timing of
administration. We will test these hypotheses through a randomized 2x2 factorial clinical trial where
participants with HIV and sepsis will be randomized to 1) empiric immediate initiation of anti-TB therapy plus
standard care or diagnosis dependent anti-TB therapy and standard care and 2) sepsis-specific dose anti-TB
therapy plus standard care or conventional WHO weight-based recommended dose anti-TB therapy and
standard care. This randomized 2x2 factorial clinical trial is strongly endorsed by Tanzanian and Ugandan
community advisory boards and will be the first to determine the optimal content, dosing, and timing of the
antimicrobial regimen for adult sepsis in sub-Saharan Africa.
项目摘要/摘要
败血症是危害疾病的综合症,被定义为威胁生命的器官功能障碍,导致宿主失调
对感染的反应,是全球死亡率的主要原因。 2017年5月,世界卫生
组织(WHO)将败血症作为全球健康优先事项。然而,关于全球败血症知之甚少
南部,特别是撒哈拉以南非洲,至少有1.2-220万例败血症和6.5例
每年因感染而导致的百万人死亡。这些患者中的大多数患有艾滋病毒。我们已经确定
该区域败血症的主要原因是结核病(TB),造成25-30%的血液
化粪池患者的感染。结核病败血症与20-50%的死亡率有关
发生在入院的前4-5天内。但是,很难在临床上或与
诊断测试通常不可用,灵敏度有限。因此,可以错过结核
结核病患者可能无法接受抗TB疗法,或者如果这样做,可能会延迟。但是,我们有
发现未经确定诊断为结核病的化粪池患者对结核病的经验治疗可改善28天
生存。我们还研究了化粪池患者的抗TB药代动力学/药效学
微生物杀死的循环药物浓度相当低。因此,我们的
假设是,与抗TB治疗相比,立即进行抗TB治疗将改善28天的生存率
仅在进行诊断后才给予,并且优化的败血症特定给药将改善28天
与传统的死亡率相比,他建议基于体重的给药
行政。我们将通过随机的2x2阶乘临床试验来检验这些假设,其中
艾滋病毒和败血症的参与者将随机分为1)抗TB治疗的经验直接开始
标准护理或诊断依赖性抗TB治疗和标准护理以及2)败血症特异性剂量抗TB
治疗加标准护理或常规的人,基于体重建议的剂量抗结核治疗和
标准护理。这项随机2x2阶乘临床试验得到坦桑尼亚和乌干达的强烈认可
社区咨询委员会,将是第一个确定最佳内容,剂量和时机的人
撒哈拉以南非洲成年败血症的抗菌治疗方案。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

暂无数据
数据更新时间:2024-06-01
Scott K Heysell的其他基金
Developing research leaders at the intersection of malnutrition and tuberculosis in Tanzania
培养坦桑尼亚营养不良和结核病交叉领域的研究领导者
- 批准号:1046156410461564
- 财政年份:2022
- 资助金额:$ 66.28万$ 66.28万
- 项目类别:
Developing research leaders at the intersection of malnutrition and tuberculosis in Tanzania
培养坦桑尼亚营养不良和结核病交叉领域的研究领导者
- 批准号:1058819710588197
- 财政年份:2022
- 资助金额:$ 66.28万$ 66.28万
- 项目类别:
Developing research leaders at the intersection of malnutrition and tuberculosis in Tanzania
培养坦桑尼亚营养不良和结核病交叉领域的研究领导者
- 批准号:1087501310875013
- 财政年份:2022
- 资助金额:$ 66.28万$ 66.28万
- 项目类别:
A randomized clinical trial of early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa
撒哈拉以南非洲地区早期经验性抗结核杆菌治疗败血症的随机临床试验
- 批准号:1008464210084642
- 财政年份:2020
- 资助金额:$ 66.28万$ 66.28万
- 项目类别:
A randomized clinical trial of early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa
撒哈拉以南非洲地区早期经验性抗结核杆菌治疗败血症的随机临床试验
- 批准号:1044382010443820
- 财政年份:2020
- 资助金额:$ 66.28万$ 66.28万
- 项目类别:
A randomized clinical trial of early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa
撒哈拉以南非洲地区早期经验性抗结核杆菌治疗败血症的随机临床试验
- 批准号:1065309410653094
- 财政年份:2020
- 资助金额:$ 66.28万$ 66.28万
- 项目类别:
Urine Colorimetry for Tuberculosis Pharmacokinetics Evaluation in Children and Adults
尿液比色法用于儿童和成人结核病药代动力学评价
- 批准号:1016871010168710
- 财政年份:2018
- 资助金额:$ 66.28万$ 66.28万
- 项目类别:
Urine Colorimetry for Tuberculosis Pharmacokinetics Evaluation in Children and Adults
尿液比色法用于儿童和成人结核病药代动力学评价
- 批准号:1022152210221522
- 财政年份:2018
- 资助金额:$ 66.28万$ 66.28万
- 项目类别:
Urine Colorimetry for Tuberculosis Pharmacokinetics Evaluation in Children and Adults
尿液比色法用于儿童和成人结核病药代动力学评价
- 批准号:1024531910245319
- 财政年份:2018
- 资助金额:$ 66.28万$ 66.28万
- 项目类别:
Urine Colorimetry for Tuberculosis Pharmacokinetics Evaluation in Children and Adults
尿液比色法用于儿童和成人结核病药代动力学评价
- 批准号:1032062010320620
- 财政年份:2018
- 资助金额:$ 66.28万$ 66.28万
- 项目类别:
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