Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial.
Creators: name: Namale, Phiona E
name: Boloko, Linda
name: Vermeulen, Marcia
name: Haigh, Kate A
name: Bagula, Fortuna
name: Maseko, Alexis
name: Sossen, Bianca
name: Lee-Jones, Scott
name: Msomi, Yoliswa
name: McIlleron, Helen
name: Mnguni, Ayanda Trevor
name: Crede, Thomas
name: Szymanski, Patryk
name: Naude, Jonathan
name: Ebrahim, Sakeena
name: Vallie, Yakoob
name: Moosa, Muhammed Shiraz
name: Bandeker, Ismail
name: Hoosain, Shakeel
name: Nicol, Mark P
name: Samodien, Nazlee
name: Centner, Chad
name: Dowling, Wentzel
name: Denti, Paolo
name: Gumedze, Freedom
name: Little, Francesca
name: Parker, Arifa
name: Price, Brendon
name: Schietekat, Denzil
name: Simmons, Bryony
name: Hill, Andrew
name: Wilkinson, Robert J
name: Oliphant, Ida
name: Hlungulu, Siphokazi
name: Apolisi, Ivy
name: Toleni, Monica
name: Asare, Zimkhitha
name: Mpalali, Mkanyiseli Kenneth
name: Boshoff, Erica
name: Prinsloo, Denise
name: Lakay, Francisco
name: Bekiswa, Abulele
name: Jackson, Amanda
name: Barnes, Ashleigh
name: Johnson, Ryan
name: Wasserman, Sean
name: Maartens, Gary
name: Barr, David
name: Schutz, Charlotte
name: Meintjes, Graeme
Publisher: name: The Francis Crick Institute
Year: 2024
Subjects: classificationCode: Infectious Disease
subject: Infectious Disease
classificationCode: Immunology
subject: Immunology
subject: FOS: Clinical medicine
classificationCode: Human Biology & Physiology
subject: Human Biology &amp; Physiology
classificationCode: Model organisms
subject: Model organisms

description: 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.