Trials (May 2024)

Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial

  • Phiona E. Namale,
  • Linda Boloko,
  • Marcia Vermeulen,
  • Kate A. Haigh,
  • Fortuna Bagula,
  • Alexis Maseko,
  • Bianca Sossen,
  • Scott Lee-Jones,
  • Yoliswa Msomi,
  • Helen McIlleron,
  • Ayanda Trevor Mnguni,
  • Thomas Crede,
  • Patryk Szymanski,
  • Jonathan Naude,
  • Sakeena Ebrahim,
  • Yakoob Vallie,
  • Muhammed Shiraz Moosa,
  • Ismail Bandeker,
  • Shakeel Hoosain,
  • Mark P. Nicol,
  • Nazlee Samodien,
  • Chad Centner,
  • Wentzel Dowling,
  • Paolo Denti,
  • Freedom Gumedze,
  • Francesca Little,
  • Arifa Parker,
  • Brendon Price,
  • Denzil Schietekat,
  • Bryony Simmons,
  • Andrew Hill,
  • Robert J. Wilkinson,
  • Ida Oliphant,
  • Siphokazi Hlungulu,
  • Ivy Apolisi,
  • Monica Toleni,
  • Zimkhitha Asare,
  • Mkanyiseli Kenneth Mpalali,
  • Erica Boshoff,
  • Denise Prinsloo,
  • Francisco Lakay,
  • Abulele Bekiswa,
  • Amanda Jackson,
  • Ashleigh Barnes,
  • Ryan Johnson,
  • Sean Wasserman,
  • Gary Maartens,
  • David Barr,
  • Charlotte Schutz,
  • Graeme Meintjes

DOI
https://doi.org/10.1186/s13063-024-08119-4
Journal volume & issue
Vol. 25, no. 1
pp. 1 – 23

Abstract

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Abstract Background HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB. Methods This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events. Discussion Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice. Trial registration ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986

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