Using biomarkers to predict TB treatment duration (Predict TB): a prospective, randomized, noninferiority, treatment shortening clinical trial
Creators: name: Chen, Ray Y
name: Via, Laura E
name: Dodd, Lori E
name: Walzl, Gerhard
name: Malherbe, Stephanus T
name: Loxton, André G
name: Dawson, Rodney
name: Wilkinson, Robert J
name: Thienemann, Friedrich
name: Tameris, Michele
name: Hatherill, Mark
name: Diacon, Andreas H
name: Liu, Xin
name: Xing, Jin
name: Jin, Xiaowei
name: Ma, Zhenya
name: Pan, Shouguo
name: Zhang, Guolong
name: Gao, Qian
name: Jiang, Qi
name: Zhu, Hong
name: Liang, Lili
name: Duan, Hongfei
name: Song, Taeksun
name: Alland, David
name: Tartakovsky, Michael
name: Rosenthal, Alex
name: Whalen, Christopher
name: Duvenhage, Michael
name: Cai, Ying
name: Goldfeder, Lisa C
name: Arora, Kriti
name: Smith, Bronwyn
name: Winter, Jill
name: Barry, Clifton E
name: Group, Predict TB Study
Publisher: name: The Francis Crick Institute
Year: 2021
Subjects: classificationCode: Model organisms
subject: Model organisms
classificationCode: Infectious Disease
subject: Infectious Disease
classificationCode: Human Biology & Physiology
subject: Human Biology &amp; Physiology
classificationCode: Immunology
subject: Immunology
subject: FOS: Clinical medicine

description: Background: 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&lt;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. Methods: 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. Discussion: 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.