Rapid urine-based screening for tuberculosis in HIV-positive patients admitted to hospital in Africa (STAMP): a pragmatic, multicentre, parallel-group, double-blind, randomised controlled trial.
Rapid urine-based screening for tuberculosis in HIV-positive patients admitted to hospital in Africa (STAMP): a pragmatic, multicentre, parallel-group, double-blind, randomised controlled trial.
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DOI：
10.1016/s0140-6736(18)31267-4
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发表时间：
2018-07-28
期刊：
影响因子：
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通讯作者：
Fielding K
中科院分区：
文献类型：
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作者：
Gupta-Wright A;Corbett EL;van Oosterhout JJ;Wilson D;Grint D;Alufandika-Moyo M;Peters JA;Chiume L;Flach C;Lawn SD;Fielding K
目前对艾滋病毒相关结核病的诊断并不理想，漏诊导致医院死亡率高，全球每年约有37.4万例艾滋病毒阳性死亡。基于尿液的检测具有良好的诊断率；因此，我们的目的是评估基于尿液筛查的hiv阳性结核病住院患者是否能改善预后。我们在马拉维和南非的两家医院进行了一项实用的、多中心的、双盲的、随机对照试验。我们纳入了18岁或以上未接受结核病治疗的艾滋病毒阳性住院患者。我们使用计算机生成的按地点分层的随机分组大小列表，将患者随机（1:1）分配到标准护理组或干预筛查组，而不考虑症状或临床表现。主治医生对护理做出决定；患者、临床医生和研究小组都不知道小组分配情况。在两组中，使用Xpert MTB/RIF检测痰液（Xpert; Cepheid, Sunnyvale， CA， USA）。在标准治疗组中，尿液样本未进行结核病检测。在干预组中，用Alere确定TB-LAM Ag （TB-LAM; Alere, Waltham， MA， USA）和expert化验法检测尿液。主要结局为全因56天死亡率。主要结局的亚组分析是基于基线CD4计数、血红蛋白、结核病的临床怀疑预先指定的；以及学习地点和时间。我们在分析中使用了意向治疗原则。该试验已在ISRCTN注册中心注册，注册号为ISRCTN71603869。在2015年10月26日至2017年9月19日期间，我们筛选了4788名hiv阳性成年人，其中2600名（54%）被随机分配到研究组（每组n=1300）。随机化后，每组有13例患者被排除在分析之外，留下2574例患者进入最终意向治疗分析（每组n=1287）。入院时，1861例患者正在接受抗逆转录病毒治疗，CD4中位数为227个细胞/ μL （IQR 79-436）。标准护理组1287例患者中有272例（21%）在56天死亡，干预组1287例患者中有235例（18%）死亡（调整后风险降低[aRD] - 2.8%, 95% CI - 5.8 - 0.3; p= 0.074）。在12个预先指定的但功能不足的亚组中，干预组的死亡率低于标准护理组，CD4细胞计数低于100 μL (aRD - 7.1%, 95% CI - 13.7至- 0.4,p=0.036)，严重贫血（- 9.0%,- 16.6至- 1.3,p= 0.021），临床疑似结核病患者（- 5.7%,- 10.9至- 0.5,p= 0.033）；没有地点或日历期间的差异。两组不良事件相似。基于尿液的结核病筛查并不能降低所有hiv阳性住院患者的总死亡率，但可能有利于一些高危亚群。实施可有助于实现降低结核病死亡率的全球目标。医学研究理事会、英国国际发展部和威康信托基金会的联合全球健康试验计划。
Current diagnostics for HIV-associated tuberculosis are suboptimal, with missed diagnoses contributing to high hospital mortality and approximately 374 000 annual HIV-positive deaths globally. Urine-based assays have a good diagnostic yield; therefore, we aimed to assess whether urine-based screening in HIV-positive inpatients for tuberculosis improved outcomes. We did a pragmatic, multicentre, double-blind, randomised controlled trial in two hospitals in Malawi and South Africa. We included HIV-positive medical inpatients aged 18 years or more who were not taking tuberculosis treatment. We randomly assigned patients (1:1), using a computer-generated list of random block size stratified by site, to either the standard-of-care or the intervention screening group, irrespective of symptoms or clinical presentation. Attending clinicians made decisions about care; and patients, clinicians, and the study team were masked to the group allocation. In both groups, sputum was tested using the Xpert MTB/RIF assay (Xpert; Cepheid, Sunnyvale, CA, USA). In the standard-of-care group, urine samples were not tested for tuberculosis. In the intervention group, urine was tested with the Alere Determine TB-LAM Ag (TB-LAM; Alere, Waltham, MA, USA), and Xpert assays. The primary outcome was all-cause 56-day mortality. Subgroup analyses for the primary outcome were prespecified based on baseline CD4 count, haemoglobin, clinical suspicion for tuberculosis; and by study site and calendar time. We used an intention-to-treat principle for our analyses. This trial is registered with the ISRCTN registry, number ISRCTN71603869. Between Oct 26, 2015, and Sept 19, 2017, we screened 4788 HIV-positive adults, of which 2600 (54%) were randomly assigned to the study groups (n=1300 for each group). 13 patients were excluded after randomisation from analysis in each group, leaving 2574 in the final intention-to-treat analysis (n=1287 in each group). At admission, 1861 patients were taking antiretroviral therapy and median CD4 count was 227 cells per μL (IQR 79–436). Mortality at 56 days was reported for 272 (21%) of 1287 patients in the standard-of-care group and 235 (18%) of 1287 in the intervention group (adjusted risk reduction [aRD] −2·8%, 95% CI −5·8 to 0·3; p=0·074). In three of the 12 prespecified, but underpowered subgroups, mortality was lower in the intervention group than in the standard-of-care group for CD4 counts less than 100 cells per μL (aRD −7·1%, 95% CI −13·7 to −0·4; p=0.036), severe anaemia (−9·0%, −16·6 to −1·3; p=0·021), and patients with clinically suspected tuberculosis (−5·7%, −10·9 to −0·5; p=0·033); with no difference by site or calendar period. Adverse events were similar in both groups. Urine-based tuberculosis screening did not reduce overall mortality in all HIV-positive inpatients, but might benefit some high-risk subgroups. Implementation could contribute towards global targets to reduce tuberculosis mortality. Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, and the Wellcome Trust.