Testing New Strategies for Patients Hospitalised With HIV-associated Disseminated Tuberculosis
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- University of Cape Town
- Enrollment
- 732
- Locations
- 2
- Primary Endpoint
- All-cause mortality
Study Overview
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.
Detailed Description
Primary efficacy endpoint:
All-cause mortality at 12 weeks
Secondary efficacy endpoint:
All-cause mortality at 2 and 24 weeks
Safety and tolerability endpoints:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
High dose Rifampicin plus Levofloxacin
Standard TB treatment plus additional Rifampicin 35 mg/kg/day PLUS Levofloxacin for 14 days
Intervention: Rifampin (Drug)
High dose Rifampicin plus Levofloxacin
Standard TB treatment plus additional Rifampicin 35 mg/kg/day PLUS Levofloxacin for 14 days
Intervention: Levofloxacin (Drug)
High dose Rifampicin plus Levofloxacin
Standard TB treatment plus additional Rifampicin 35 mg/kg/day PLUS Levofloxacin for 14 days
Intervention: Rifampicin, Pyrazinamide, Ethambutol and Isoniazid (Drug)
Prednisone
Prednisone 1.5 mg/kg for 14 days
Intervention: Prednisone (Drug)
Standard TB treatment
High dose rifampicin/levofloxacin comparator
Intervention: Rifampicin, Pyrazinamide, Ethambutol and Isoniazid (Drug)
Placebo
Prednisone comparator
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
All-cause mortality
Time Frame: 12 weeks
Secondary Outcomes
- All-cause mortality(2 and 24 weeks respectively)
- In-hospital mortality during index admission(7 days)
Investigators
Charlotte Schutz
Co-Principal Investigator
University of Cape Town