Testing Novel Strategies for Patients Hospitalized with HIV-associated Disseminated Tuberculosis (NewStrat-TB): Protocol for a Randomised Controlled Trial
Author:
Namale Phiona E1ORCID, Boloko Linda2, Vermeulen Marcia2, Haigh Kate A2, Bagula Fortuna2, Maseko Alexis2, Sossen Bianca2, Lee-Jones Scott3, Msomi Yoliswa2, Mclleron Helen2, Mnguni Ayanda T3, Crede Thomas2, Szymanski Patryk2, Naude Jonathan2, Ebrahim Sakeena2, Vallie Yakoob1, Moosa Muhammed S2, Bandeker Ismail2, Hoosain Shakeel2, Nicol Mark P2, Samodien Nazlee4, Centner Chad5, Dowling Wentzel1, Denti Paolo2, Gumedze Freedom6, Little Francesca6, Parker Arifa3, Price Brendon7, Schietekat Denzil3, Simmons Bryony8, Hill Andrew9, Wilkinson Robert2, Oliphant Ida2, Hlungulu Siphokazi2, Apolisi Ivy2, Toleni Monica2, Asare Zimkhitha2, Mpalali Mkanyiseli K2, Boshoff Erica2, Prinsloo Denise2, Lakay Francisco2, Bekiswa Abulele2, Jackson Amanda2, Barnes Ashleigh2, Johnson Ryan2, Wasserman Sean2, Maartens Gary2, Barr David2, Schutz Charlotte2, Meintjes Graeme10
Affiliation:
1. University of Cape Town Faculty of Health Sciences 2. UCT Faculty of Health Sciences: University of Cape Town Faculty of Health Sciences 3. Stellenbosch University - Tygerberg Campus: Stellenbosch University Faculty of Medicine and Health Sciences 4. NHLS: National Health Laboratory Service 5. National Health Laboratory Service 6. UCT Department of Statistical Sciences: University of Cape Town Department of Statistical Sciences 7. UCT Department of Pathology: University of Cape Town Department of Pathology 8. The London School of Economics and Political Science Department of Economics 9. London School of Economics Department of Industrial Relations: The London School of Economics and Political Science Department of Management 10. UCT FHS: University of Cape Town Faculty of Health Sciences
Abstract
Abstract
Background
HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalized 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 2x2 factorial design: 1) high dose rifampicin (35mg/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.
ClinicalTrials.gov ID: NCT04951986. Trial registration Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986
Publisher
Research Square Platform LLC
Reference81 articles.
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