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

  1. Phiona E. Namale
  2. Linda Boloko
  3. Marcia Vermeulen
  4. Kate A. Haigh
  5. Fortuna Bagula
  6. Alexis Maseko
  7. Bianca Sossen
  8. Scott Lee-Jones
  9. Yoliswa Msomi
  10. Helen McIlleron
  11. Ayanda Trevor Mnguni
  12. Thomas Crede
  13. Patryk Szymanski
  14. Jonathan Naude
  15. Sakeena Ebrahim
  16. Yakoob Vallie
  17. Muhammed Shiraz Moosa
  18. Ismail Bandeker
  19. Shakeel Hoosain
  20. Mark P. Nicol
  21. Nazlee Samodien
  22. Chad Centner
  23. Wentzel Dowling
  24. Paolo Denti
  25. Freedom Gumedze
  26. Francesca Little
  27. Arifa Parker
  28. Brendon Price
  29. Denzil Schietekat
  30. Bryony Simmons
  31. Andrew Hill
  32. Robert J. Wilkinson
  33. Ida Oliphant
  34. Siphokazi Hlungulu
  35. Ivy Apolisi
  36. Monica Toleni
  37. Zimkhitha Asare
  38. Mkanyiseli Kenneth Mpalali
  39. Erica Boshoff
  40. Denise Prinsloo
  41. Francisco Lakay
  42. Abulele Bekiswa
  43. Amanda Jackson
  44. Ashleigh Barnes
  45. Ryan Johnson
  46. Sean Wasserman
  47. Gary Maartens
  48. David Barr
  49. Charlotte Schutz
  50. Graeme Meintjes
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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

Article activity feed

  1. Version published to 10.1186/s13063-024-08119-4
  2. Version published to 10.21203/rs.3.rs-3869003/v1 on Research Square