Using biomarkers to predict TB treatment duration (Predict TB): a prospective, randomized, noninferiority, treatment shortening clinical trial

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Title: Using biomarkers to predict TB treatment duration (Predict TB): a prospective, randomized, noninferiority, treatment shortening clinical trial
Authors: Chen, RY
Via, LE
Dodd, LE
Walzl, G
Malherbe, ST
Loxton, AG
Dawson, R
Wilkinson, RJ
Thienemann, F
Tameris, M
Hatherill, M
Diacon, AH
Liu, X
Xing, J
Jin, X
Ma, Z
Pan, S
Zhang, G
Gao, Q
Jiang, Q
Zhu, H
Liang, L
Duan, H
Song, T
Alland, D
Tartakovsky, M
Rosenthal, A
Whalen, C
Duvenhage, M
Cai, Y
Goldfeder, LC
Arora, K
Smith, B
Winter, J
Barry Iii, CE
Predict TB Study Group
Item Type: Journal Article
Abstract: 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<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.
Issue Date: 6-Nov-2017
Date of Acceptance: 6-Oct-2017
ISSN: 2572-4754
Publisher: F1000Research
Start Page: 9
End Page: 9
Journal / Book Title: Gates Open Research
Volume: 1
Copyright Statement: © 2017 Chen RY et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The author(s) is/are employees of the US Government and therefore domestic copyright protection in USA does not apply to this work. The work may be protected under the copyright laws of other jurisdictions when used in those jurisdictions.
Sponsor/Funder: European and Developing Countries Clinical Trials Partnership
Funder's Grant Number: SRIA2015-1065
Keywords: GeneXpert
cycle threshold
drug sensitive
pulmonary tuberculosis
treatment shortening
Publication Status: Published
Conference Place: United States
Open Access location:
Appears in Collections:Department of Medicine

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