Auld Andrew F, Agizew Tefera, Pals Sherri, Finlay Alyssa, Ndwapi Ndwapi, Boyd Rosanna, Alexander Heather, Mathoma Anikie, Basotli Joyce, Gwebe-Nyirenda Sambayawo, Shepherd James, Ellerbrock Tedd V, Date Anand
Division of Global HIV & TB, Center for Global Health, United States Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, Atlanta, GA, 30333, USA.
Centers for Disease Control and Prevention Botswana, Plot 14818 Lebatlane Road, Gaborone, Botswana.
BMC Infect Dis. 2016 Oct 26;16(1):606. doi: 10.1186/s12879-016-1905-4.
In 2012, as a pilot for Botswana's national Xpert MTB/RIF (Xpert) rollout plans, intensified tuberculosis (TB) case finding (ICF) activities were strengthened at 22 HIV treatment clinics prior to phased activation of 13 Xpert instruments. Together, the strengthened ICF intervention and Xpert activation are referred to as the "Xpert package".
The evaluation, called the Xpert Package Rollout Evaluation using a Stepped-wedge design (XPRES), has two key objectives: (1) to compare sensitivity of microscopy-based and Xpert-based pulmonary TB diagnostic algorithms in diagnosing sputum culture-positive TB; and (2) to evaluate impact of the "Xpert package" on all-cause, 6-month, adult antiretroviral therapy (ART) mortality. A pragmatic, stepped-wedge cluster-randomized trial design was chosen. The design involves enrollment of three cohorts: (1) cohort R, a retrospective cohort of all study clinic ART enrollees in the 24 months before study initiation (July 31, 2012); (2) cohort A, a prospective cohort of all consenting patients presenting to study clinics after study initiation, who received the ICF intervention and the microscopy-based TB diagnostic algorithm; and (3) cohort B, a prospective cohort of all consenting patients presenting to study clinics after Xpert activation, who received the ICF intervention and the Xpert-based TB diagnostic algorithm. TB diagnostic sensitivity will be compared between TB culture-positive enrollees in cohorts A and B. All-cause, 6-month ART-mortality will be compared between cohorts R and B. With anticipated cohort R, A, and B sample sizes of about 10,131, 1,878, and 4,258, respectively, the study is estimated to have >80 % power to detect differences in pre-versus post-Xpert TB diagnostic sensitivity if pre-Xpert sensitivity is ≤52.5 % and post-Xpert sensitivity ≥82.5 %, and >80 % power to detect a 40 % reduction in all-cause, 6-month, ART mortality between cohorts R and B if cohort R mortality is ≥13/100 person-years.
Only one small previous trial (N = 424) among ART enrolees in Zimbabwe evaluated, in a secondary analysis, Xpert impact on all-cause 6-month ART mortality. No mortality impact was observed. This Botswana trial, with its larger sample size and powered specifically to detect differences in all-cause 6-month ART mortality, remains well-positioned to contribute understanding of Xpert impact.
Retrospectively registered at ClinicalTrials.gov: NCT02538952 .
2012年，作为博茨瓦纳国家Xpert MTB/RIF（Xpert）推广计划的试点，在逐步启用13台Xpert仪器之前，22家艾滋病毒治疗诊所加强了强化结核病（TB）病例发现（ICF）活动。强化的ICF干预措施与Xpert启用措施合称为“Xpert套餐”。
这项名为“使用阶梯楔形设计的Xpert套餐推广评估（XPRES）”的评估有两个关键目标：（1）比较基于显微镜检查和基于Xpert的肺结核诊断算法在诊断痰培养阳性结核病方面的敏感性；（2）评估“Xpert套餐”对全因、6个月成人抗逆转录病毒治疗（ART）死亡率的影响。选择了一种实用的阶梯楔形整群随机试验设计。该设计涉及招募三个队列：（1）队列R，为研究开始前24个月（2012年7月31日）所有研究诊所接受ART治疗的入组者的回顾性队列；（2）队列A，为研究开始后到研究诊所就诊的所有同意参与的患者的前瞻性队列，这些患者接受了ICF干预措施和基于显微镜检查的结核病诊断算法；（3）队列B，为Xpert启用后到研究诊所就诊的所有同意参与的患者的前瞻性队列，这些患者接受了ICF干预措施和基于Xpert的结核病诊断算法。将比较队列A和队列B中痰培养阳性的结核病入组者的结核病诊断敏感性。将比较队列R和队列B的全因、6个月ART死亡率。预期队列R、A和B的样本量分别约为10131、1878和4258，估计该研究有超过80%的把握度检测到Xpert启用前后结核病诊断敏感性的差异，前提是Xpert启用前的敏感性≤52.5%且启用后的敏感性≥82.5%，并且如果队列R的死亡率≥13/100人年，有超过80%的把握度检测到队列R和队列B之间全因、6个月ART死亡率降低40%。
在津巴布韦接受ART治疗的入组者中，之前仅有一项小型试验（N = 424）在二次分析中评估了Xpert对全因6个月ART死亡率的影响。未观察到死亡率影响。博茨瓦纳的这项试验样本量更大，专门旨在检测全因6个月ART死亡率的差异，仍然很有条件增进对Xpert影响的理解。
在ClinicalTrials.gov进行回顾性注册：NCT02538952 。
