Treatment Strategy for Rifampin-Susceptible Tuberculosis

Abstract

BACKGROUND: Tuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear. METHODS: In this adaptive, open-label, noninferiority trial, we randomly assigned participants with rifampin-susceptible pulmonary tuberculosis to undergo either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks) or a strategy involving initial treatment with an 8-week regimen, extended treatment for persistent clinical disease, monitoring after treatment, and retreatment for relapse. There were four strategy groups with different initial regimens; noninferiority was assessed in the two strategy groups with complete enrollment, which had initial regimens of high-dose rifampin-linezolid and bedaquiline-linezolid (each with isoniazid, pyrazinamide, and ethambutol). The primary outcome was a composite of death, ongoing treatment, or active disease at week 96. The noninferiority margin was 12 percentage points. RESULTS: Of the 674 participants in the intention-to-treat population, 4 (0.6%) withdrew consent or were lost to follow-up. A primary-outcome event occurred in 7 of the 181 participants (3.9%) in the standard-treatment group, as compared with 21 of the 184 participants (11.4%) in the strategy group with an initial rifampin-linezolid regimen (adjusted difference, 7.4 percentage points; 97.5% confidence interval [CI], 1.7 to 13.2; noninferiority not met) and 11 of the 189 participants (5.8%) in the strategy group with an initial bedaquiline-linezolid regimen (adjusted difference, 0.8 percentage points; 97.5% CI, -3.4 to 5.1; noninferiority met). The mean total duration of treatment was 180 days in the standard-treatment group, 106 days in the rifampin-linezolid strategy group, and 85 days in the bedaquiline-linezolid strategy group. The incidences of grade 3 or 4 adverse events and serious adverse events were similar in the three groups. CONCLUSIONS: A strategy involving initial treatment with an 8-week bedaquiline-linezolid regimen was noninferior to standard treatment for tuberculosis with respect to clinical outcomes. The strategy was associated with a shorter total duration of treatment and with no evident safety concerns. (Funded by the Singapore National Medical Research Council and others; TRUNCATE-TB ClinicalTrials.gov number, NCT03474198.).

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References 25

1. 1.

   Global tuberculosis report 2021. 2021.

   Not in our library

2. 2.

   WHO consolidated guidelines on tuberculosis: module 4: treatment: drug-susceptible tuberculosis treatment. 2022.

   Not in our library

3. 3.

   Chaves Torres NM, Quijano Rodríguez JJ, Porras Andrade PS, Arriaga MB, Netto EM. Factors predictive of the success of tuberculosis treatment: a systematic review with meta-analysis. PLoS One. 2019;14(12):e0226507.

   Not in our library10.1371/journal.pone.0226507

4. 4.

   Chakaya J, Khan M, Ntoumi F, et al. Global Tuberculosis Report 2020 — reflections on the global TB burden, treatment and prevention efforts. Int J Infect Dis. 2021;113(Suppl 1):S7-S12.

   Not in our library10.1016/j.ijid.2021.02.107

5. 5.

   Gelband H. Regimens of less than six months for treating tuberculosis. Cochrane Database Syst Rev. 1999;2:CD001362.

   Not in our library10.1002/14651858.cd001362

6. 6.

   Gillespie SH, Crook AM, McHugh TD, et al. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med. 2014;371:1577-87.

   Not in our library10.1056/nejmoa1407426

7. 7.

   Jindani A, Harrison TS, Nunn AJ, et al. High-dose rifapentine with moxifloxacin for pulmonary tuberculosis. N Engl J Med. 2014;371:1599-608.

   Not in our library10.1056/nejmoa1314210

8. 8.

   Merle CS, Fielding K, Sow OB, et al. A four-month gatifloxacin-containing regimen for treating tuberculosis. N Engl J Med. 2014;371:1588-98.

   Not in our library10.1056/nejmoa1315817

9. 9.

   Dorman SE, Nahid P, Kurbatova EV, et al. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. N Engl J Med. 2021;384:1705-18.

   Not in our library10.1056/nejmoa2033400

10. 10.

    Fox W. Whither short-course chemotherapy? Br J Dis Chest. 1981;75:331-57.

    Not in our library10.1016/0007-0971(81)90022-x

11. 11.

    Sputum-smear-negative pulmonary tuberculosis: controlled trial of 3-month and 2-month regimens of chemotherapy. Lancet. 1979;1:1361-3.

    Not in our library

12. 12.

    Division of AIDS table for grading the severity of adult and pediatric adverse events, version 1.0. 2004.

    Not in our library

13. 13.

    Hnizdo E, Singh T, Churchyard G. Chronic pulmonary function impairment caused by initial and recurrent pulmonary tuberculosis following treatment. Thorax. 2000;55:32-8.

    Not in our library10.1136/thorax.55.1.32

14. 14.

    Grace AG, Mittal A, Jain S, et al. Shortened treatment regimens versus the standard regimen for drug-sensitive pulmonary tuberculosis. Cochrane Database Syst Rev. 2019;12:CD012918.

    Not in our library10.1002/14651858.cd012918.pub2

15. 15.

    Holdiness MR. Clinical pharmacokinetics of clofazimine: a review. Clin Pharmacokinet. 1989;16:74-85.

    Not in our library10.2165/00003088-198916020-00002

16. 16.

    van Heeswijk RPG, Dannemann B, Hoetelmans RM. Bedaquiline: a review of human pharmacokinetics and drug-drug interactions. J Antimicrob Chemother. 2014;69:2310-8.

    Not in our library10.1093/jac/dku171

17. 17.

    Mallick JS, Nair P, Abbew ET, Van Deun A, Decroo T. Acquired bedaquiline resistance during the treatment of drug-resistant tuberculosis: a systematic review. JAC Antimicrob Resist. 2022;4:dlac029.

    Not in our library10.1093/jacamr/dlac029

18. 18.

    Ismail NA, Omar SV, Moultrie H, et al. Assessment of epidemiological and genetic characteristics and clinical outcomes of resistance to bedaquiline in patients treated for rifampicin-resistant tuberculosis: a cross-sectional and longitudinal study. Lancet Infect Dis. 2022;22:496-506.

    Not in our library10.1016/s1473-3099(21)00470-9

19. 19.

    Fox WS, Strydom N, Imperial MZ, Jarlsberg L, Savic RM. Examining nonadherence in the treatment of tuberculosis: the patterns that lead to failure. Br J Clin Pharmacol. 2022.

    Not in our library10.1111/bcp.15515

20. 20.

    Vernon A, Fielding K, Savic R, Dodd L, Nahid P. The importance of adherence in tuberculosis treatment clinical trials and its relevance in explanatory and pragmatic trials. PLoS Med. 2019;16:e1002884.

    Not in our library10.1371/journal.pmed.1002884

21. 21.

    Conradie F, Bagdasaryan TR, Borisov S, et al. Bedaquiline–pretomanid–linezolid regimens for drug-resistant tuberculosis. N Engl J Med. 2022;387:810-23.

    Not in our library10.1056/nejmoa2119430

22. 22.
    A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis · 2018

    Corrected
23. 23.

    Johnson JL, Hadad DJ, Dietze R, et al. Shortening treatment in adults with non-cavitary tuberculosis and 2-month culture conversion. Am J Respir Crit Care Med. 2009;180:558-63.

    Not in our library10.1164/rccm.200904-0536oc

24. 24.

    Sutherland JS, van der Spuy G, Gindeh A, et al. Diagnostic accuracy of the Cepheid 3-gene host response fingerstick blood test in a prospective, multisite study: interim results. Clin Infect Dis. 2022;74:2136-41.

    Not in our library10.1093/cid/ciab839

25. 25.
    Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study · 2020

    No notice

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