Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial.
Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial.
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撒哈拉以南非洲败血症的早期经验性抗结核分枝杆菌治疗：随机临床试验方案。
DOI：
10.1136/bmjopen-2022-061953
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发表时间：
2022-06-06
期刊：
影响因子：
2.9
通讯作者：
Mpagama, Stellah G.
中科院分区：
文献类型：
--
作者：
Said, Bibie;Nuwagira, Edwin;Liyoyo, Alphonce;Arinaitwe, Rinah;Gitige, Catherine;Mushagara, Rhina;Buzaare, Peter;Chongolo, Anna;Jjunju, Samuel;Twesigye, Precious;Boulware, David R.;Conaway, Mark;Null, Megan;Thomas, Tania A.;Heysell, Scott K.;Moore, Christopher C.;Muzoora, Conrad;Mpagama, Stellah G.
撒哈拉以南非洲承担着全球脓毒症和相关死亡率的最高负担。在艾滋病毒和结核病（TB）高流行的环境中，如撒哈拉以南非洲，TB是败血症的主要原因。然而，抗结核治疗通常被延迟，并且在脓毒症患者中可能无法达到足够的血药浓度。因此，这项多中心随机临床试验旨在确定立即和/或增加剂量的抗结核治疗是否能改善坦桑尼亚或乌干达感染艾滋病毒和败血症的参与者的28天死亡率。这是一项III期、多中心、开放标签、随机对照临床2×2析因优效性试验，研究（1）立即开始抗结核治疗和（2）在坦桑尼亚或乌干达住院的HIV和脓毒症成人患者中，除标准治疗抗菌药物外，还进行脓毒症特异性剂量抗结核治疗。主要终点是28天死亡率。436例受试者的样本量将提供80%的把握度来检验时间和剂量对28天死亡率的每种主要影响，双侧显著性水平为5%。绝对风险降低的预期主效应为13%，风险降低的预期OR为1.58。这项临床试验将确定在艾滋病毒和结核病高发环境中脓毒症抗菌治疗的最佳内容、剂量和时机。这项研究由美国国立卫生研究院资助。弗吉尼亚大学、坦桑尼亚国家医学研究所和乌干达国家科学和技术理事会授予了机构审查委员会的批准。研究结果将在坦桑尼亚和乌干达的同行评审期刊和大众媒体上发表。我们还将向我们在研究准备期间召集的社区咨询委员会提交我们的调查结果。ClinicalTrials.gov（NCT 04618198）。
Sub-Saharan Africa shoulders the highest burden of global sepsis and associated mortality. In high HIV and tuberculosis (TB) prevalent settings such as sub-Saharan Africa, TB is the leading cause of sepsis. However, anti-TB therapy is often delayed and may not achieve adequate blood concentrations in patients with sepsis. Accordingly, this multisite randomised clinical trial aims to determine whether immediate and/or increased dose anti-TB therapy improves 28-day mortality for participants with HIV and sepsis in Tanzania or Uganda. This is a phase 3, multisite, open-label, randomised controlled clinical 2×2 factorial superiority trial of (1) immediate initiation of anti-TB therapy and (2) sepsis-specific dose anti-TB therapy in addition to standard of care antibacterials for adults with HIV and sepsis admitted to hospital in Tanzania or Uganda. The primary endpoint is 28-day mortality. A sample size of 436 participants will provide 80% power for testing each of the main effects of timing and dose on 28-day mortality with a two-sided significance level of 5%. The expected main effect for absolute risk reduction is 13% and the expected OR for risk reduction is 1.58. This clinical trial will determine the optimal content, dosing and timing of antimicrobial therapy for sepsis in high HIV and TB prevalent settings. The study is funded by the National Institutes of Health in the US. Institutional review board approval was conferred by the University of Virginia, the Tanzania National Institute for Medical Research, and the Uganda National Council for Science and Technology. Study results will be published in peer-reviewed journals and in the popular press of Tanzania and Uganda. We will also present our findings to the Community Advisory Boards that we convened during study preparation. ClinicalTrials.gov (NCT04618198).
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影响因子：
8.8
作者：
Jacob ST;Banura P;Baeten JM;Moore CC;Meya D;Nakiyingi L;Burke R;Horton CL;Iga B;Wald A;Reynolds SJ;Mayanja-Kizza H;Scheld WM;Promoting Resource-Limited Interventions for Sepsis Management in Uganda Study Group
通讯作者：
Promoting Resource-Limited Interventions for Sepsis Management in Uganda Study Group
影响因子：
1.9
作者：
OBRIEN, PC;FLEMING, TR
通讯作者：
FLEMING, TR
影响因子：
158.5
作者：
Blanc, Francois-Xavier;Badje, Anani D.;Laureillard, Didier
通讯作者：
Laureillard, Didier
影响因子：
3
作者：
Auma MA;Siedner MJ;Nyehangane D;Nalusaji A;Nakaye M;Mwanga-Amumpaire J;Muhindo R;Wilson LA;Boum Y 2nd;Moore CC
通讯作者：
Moore CC
影响因子：
120.7
作者：
Hernandez, Glenn;Ospina-Tascon, Gustavo A.;Bakker, Jan
通讯作者：
Bakker, Jan