Testing New Strategies for Patients Hospitalised With HIV-associated Disseminated Tuberculosis

NCT04951986 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: HREC REF: 001/2021
• Study Type: interventional
• Target: 732
• Locations: 1 country
• Sites: 2

Brief Summary

The New Strat-TB trial is a superiority Phase III randomised control clinical trial with a 2X2 factorial design. The main aim of the study is to assess the efficacy and safety of high dose rifampicin and levofloxacin for 14 days in addition to standard TB therapy with or without steroids among adults hospitalized with HIV-associated disseminated tuberculosis. The investigators hypothesize that intensified treatment with increased rifampicin doses at 35 mg/kg plus levofloxacin will more rapidly reduce the mycobacterial load. The investigators also hypothesize that steroids will have an immune-modulatory effect and dampen the activation of the innate immune system. The investigators hypothesize that these two strategies will lead to improved survival in patients hospitalized with HIV-associated disseminated tuberculosis.

Conditions

HIV; Disseminated Tuberculosis

Keywords

HIV; High dose rifampicin; Fluoroquinolones; Glucocorticoids; Antiretroviral therapy

Outcome Measures

Primary Outcomes (1)

• All-cause mortality

  12 weeks

Secondary Outcomes (2)

• In-hospital mortality during index admission

  7 days

• All-cause mortality

  2 and 24 weeks respectively

Study Arms (4)

High dose Rifampicin plus Levofloxacin

EXPERIMENTAL

Standard TB treatment plus additional Rifampicin 35 mg/kg/day PLUS Levofloxacin for 14 days

Drug: Rifampin; Drug: Levofloxacin; Drug: Rifampicin, Pyrazinamide, Ethambutol and Isoniazid

Prednisone

EXPERIMENTAL

Prednisone 1.5 mg/kg for 14 days

Drug: Prednisone

Standard TB treatment

ACTIVE COMPARATOR

High dose rifampicin/levofloxacin comparator

Drug: Rifampicin, Pyrazinamide, Ethambutol and Isoniazid

Placebo

PLACEBO COMPARATOR

Prednisone comparator

Drug: Placebo

Interventions

Rifampin DRUG

Rifampicin up to 35 mg/kg/day for 14 days

Also known as: rifampicin, Rifadin, Rimactane

High dose Rifampicin plus Levofloxacin

Levofloxacin DRUG

Levofloxacin 750mg daily (for weight \<50kg) or 1 g daily (for weight \>50 kg) daily for 14 days

High dose Rifampicin plus Levofloxacin

Rifampicin, Pyrazinamide, Ethambutol and Isoniazid DRUG

Rifampicin 10 mg/kg; Isoniazid 5 mg/kg; Pyrazinamide 15 mg/kg; Ethambutol15 mg/kg in fixed dose combination administered per weight band. Standard of care control arm

Also known as: Rifafour

High dose Rifampicin plus Levofloxacin; Standard TB treatment

Prednisone DRUG

Prednisone 1.5mg/kg/day for 14 days

Also known as: Trolic

Prednisone

Placebo DRUG

Placebo identical to Prednisone

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged \>18
• HIV infection
• Disseminated TB confirmed by one or more of the following tests being positive
• Lysed blood Xpert Ultra positive for MTB
• Concentrated urine Xpert Ultra positive for MTB
• Urine Alere LAM positive
• Hospital clinical team made decision to initiate TB treatment

You may not qualify if:

• Pregnant or breastfeeding
• Active or recent SARS-CoV-2 infection
• TB treatment within the last 1 month or more than 2 doses of TB treatment
• Rifampicin resistance
• Neurological TB
• Receiving corticosteroids or other immunosuppressive therapy
• ALT \>120 IU/L or total bilirubin \>34 μmol/L
• Plasma CrAg positive or cryptococcal meningitis
• Current malignancy requiring active treatment (including any Kaposi sarcoma lesions)
• Patients established on ART with Protease Inhibitor based regimen who cannot be switched to a dolutegravir based regimen
• Diabetic ketoacidosis or Hyperosmolar Non-ketotic acidosis
• Any condition in the opinion of the investigator for which participation would increase risk to the patient

Sponsors & Collaborators

• University of Cape Town: lead

Study Sites (2)

Khayelitsha Hospital, c/o Steve Biko and Walter Sisulu Drives, Khayelitsha

Cape Town, Western Cape, 7784, South Africa

Location

Mitchells Plain Hospital, Mitchells PLain

Cape Town, Western Cape, 7785, South Africa

Location

Related Publications (1)

• Namale PE, Boloko L, Vermeulen M, Haigh KA, Bagula F, Maseko A, Sossen B, Lee-Jones S, Msomi Y, McIlleron H, Mnguni AT, Crede T, Szymanski P, Naude J, Ebrahim S, Vallie Y, Moosa MS, Bandeker I, Hoosain S, Nicol MP, Samodien N, Centner C, Dowling W, Denti P, Gumedze F, Little F, Parker A, Price B, Schietekat D, Simmons B, Hill A, Wilkinson RJ, Oliphant I, Hlungulu S, Apolisi I, Toleni M, Asare Z, Mpalali MK, Boshoff E, Prinsloo D, Lakay F, Bekiswa A, Jackson A, Barnes A, Johnson R, Wasserman S, Maartens G, Barr D, Schutz C, Meintjes G. Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial. Trials. 2024 May 8;25(1):311. doi: 10.1186/s13063-024-08119-4.

  PMID: 38720383 DERIVED

MeSH Terms

Interventions

Rifampin; Levofloxacin; Pyrazinamide; Ethambutol; Isoniazid; Prednisone

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Pyrazines; Heterocyclic Compounds, 1-Ring; Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals; Hydrazines; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Principal Investigator

Model Details: First intervention (open label): a) Experimental arm: Standard first-line anti-tuberculosis therapy plus additional rifampicin to reach 35mg/kg/day for 14 days plus levofloxacin 750mg/day for weight \<50kg and 1g/day for weight \>50kg for 14 days b) Control arm: Standard TB therapy containing rifampicin 10mg/kg for 14 days (standard of care) After 14 days both study arms will continue standard TB therapy with rifampicin at 10mg/kg to complete 2 months of intensive phase in total. This will be followed by standard continuation phase TB therapy. 2\. Second intervention (double-blind): 1. Experimental arm: Prednisone 1.5mg/kg per day for 14 days 2. Control arm: Identical placebo for 14 days

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: July 7, 2021
• Study Start: August 11, 2021
• Primary Completion: December 15, 2025
• Study Completion: March 1, 2026
• Last Updated: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE

Locations

ZA (2)