使用生物标志物预测结核病治疗疗程（预测结核病）：一项前瞻性、随机、非劣效性、缩短治疗时间的临床试验。
Using biomarkers to predict TB treatment duration (Predict TB): a prospective, randomized, noninferiority, treatment shortening clinical trial.
作者信息
Chen Ray Y, Via Laura E, Dodd Lori E, Walzl Gerhard, Malherbe Stephanus T, Loxton André G, Dawson Rodney, Wilkinson Robert J, Thienemann Friedrich, Tameris Michele, Hatherill Mark, Diacon Andreas H, Liu Xin, Xing Jin, Jin Xiaowei, Ma Zhenya, Pan Shouguo, Zhang Guolong, Gao Qian, Jiang Qi, Zhu Hong, Liang Lili, Duan Hongfei, Song Taeksun, Alland David, Tartakovsky Michael, Rosenthal Alex, Whalen Christopher, Duvenhage Michael, Cai Ying, Goldfeder Lisa C, Arora Kriti, Smith Bronwyn, Winter Jill, Barry Iii Clifton E
机构信息
Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Wellcome Centre for Infectious Diseases Research in Africa,Institute of Infectious Disease and Molecular Medicine, University of Cape Town (UCT), Cape Town, South Africa.
出版信息
Gates Open Res. 2017 Nov 6;1:9. doi: 10.12688/gatesopenres.12750.1.
UNLABELLED
: By the early 1980s, tuberculosis treatment was shortened from 24 to 6 months, maintaining relapse rates of 1-2%. Subsequent trials attempting shorter durations have failed, with 4-month arms consistently having relapse rates of 15-20%. One trial shortened treatment only among those without baseline cavity on chest x-ray and whose month 2 sputum culture converted to negative. The 4-month arm relapse rate decreased to 7% but was still significantly worse than the 6-month arm (1.6%, P<0.01). We hypothesize that PET/CT characteristics at baseline, PET/CT changes at one month, and markers of residual bacterial load will identify patients with tuberculosis who can be cured with 4 months (16 weeks) of standard treatment. : This is a prospective, multicenter, randomized, phase 2b, noninferiority clinical trial of pulmonary tuberculosis participants. Those eligible start standard of care treatment. PET/CT scans are done at weeks 0, 4, and 16 or 24. Participants who do not meet early treatment completion criteria (baseline radiologic severity, radiologic response at one month, and GeneXpert-detectable bacilli at four months) are placed in Arm A (24 weeks of standard therapy). Those who meet the early treatment completion criteria are randomized at week 16 to continue treatment to week 24 (Arm B) or complete treatment at week 16 (Arm C). The primary endpoint compares the treatment success rate at 18 months between Arms B and C. : Multiple biomarkers have been assessed to predict TB treatment outcomes. This study uses PET/CT scans and GeneXpert (Xpert) cycle threshold to risk stratify participants. PET/CT scans are not applicable to global public health but could be used in clinical trials to stratify participants and possibly become a surrogate endpoint. If the Predict TB trial is successful, other immunological biomarkers or transcriptional signatures that correlate with treatment outcome may be identified.
TRIAL REGISTRATION
NCT02821832.
未标注
到20世纪80年代初，结核病治疗疗程从24个月缩短至6个月，复发率维持在1%-2%。随后尝试更短疗程的试验均告失败，4个月疗程组的复发率始终在15%-20%。一项试验仅对胸部X线检查无基线空洞且第2个月痰培养转阴的患者缩短治疗疗程。4个月疗程组的复发率降至7%，但仍显著高于6个月疗程组（1.6%，P<0.01）。我们推测，基线时的PET/CT特征、1个月时的PET/CT变化以及残余细菌载量标志物将能识别出可通过4个月（16周）标准治疗治愈的结核病患者。 这是一项针对肺结核参与者的前瞻性、多中心、随机、2b期、非劣效性临床试验。符合条件者开始接受标准治疗。在第0、4和16或24周进行PET/CT扫描。未达到早期治疗完成标准（基线放射学严重程度、1个月时的放射学反应以及4个月时GeneXpert检测到的杆菌）的参与者被分入A组（24周标准治疗）。达到早期治疗完成标准的参与者在第16周被随机分组，继续治疗至第24周（B组）或在第16周完成治疗（C组）。主要终点是比较B组和C组在18个月时的治疗成功率。 已评估多种生物标志物以预测结核病治疗结果。本研究使用PET/CT扫描和GeneXpert循环阈值对参与者进行风险分层。PET/CT扫描不适用于全球公共卫生，但可用于临床试验对参与者进行分层，并可能成为替代终点。如果“预测结核病”试验成功，可能会识别出其他与治疗结果相关的免疫生物标志物或转录特征。
试验注册
NCT02821832
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