Testing New Strategies for Patients Hospitalised With HIV-associated Disseminated Tuberculosis (NEW-STRAT TB)

  • STATUS
    Recruiting
  • End date
    Dec 31, 2024
  • participants needed
    732
  • sponsor
    University of Cape Town
Updated on 23 April 2022

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.

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:

  • Occurrence of hepatotoxicity using the American Thoracic Society (ATS) hepatotoxicity criteria: Alanine aminotransferase (ALT) elevation of more than three times the upper limit of normal (ULN) in the presence of hepatitis symptoms and/or jaundice or five times the upper limit of normal in the absence of symptoms.
  • Corticosteroid-associated adverse events, classified by severity and relation to study drug and will be reported if these develop within 4 weeks of enrolment. These will include new hypertension, new poor blood pressure control in a known hypertensive, hyperglycaemia, hypomania, mania, depression, acne, gastritis symptoms, upper gastrointestinal bleeding, and avascular bone necrosis.
  • Laboratory safety data (Grade 3 and 4 abnormalities using the ACTG grading system): liver function tests (alanine and aspartate aminotransferase[ALT, AST], gammaglutamyl transferase [GGT], alkaline phosphatase [ALP], International Normalized Ratio [INR], conjugated and total bilirubin [CBR, TBR]), glucose, full blood counts (including white cell, neutrophil and platelet counts plus haemoglobin) and electrolytes (sodium, potassium) and creatinine.
  • Occurrence of other opportunistic infections (AIDS-related, bacterial, fungal and viral) and malignancies (Kaposi's sarcoma) up to 12 weeks.
  • Occurrence of paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in patients starting antiretroviral therapy up to 12 weeks.
  • All grade 3 and 4 clinical adverse events (using the ACTG grading system)
  • Serious adverse events
  • Adverse events requiring study drug interruption and or withdrawal
  • Adverse drug reactions attributed to study drug

Follow-up:

Participants will be followed up daily while admitted to hospital for assessment of adverse events. Safety and routine blood tests will be done on day 2, 4, 7, 14 and 28. Further visits will be on week 12 and 24.

Data monitoring:

The trial will be monitored by an independent Data and Safety Monitoring Board (DSMB) comprising 4 independent researchers and an independent statistician. If there is evidence of harm related to study medication or trial conduct the DSMB may advise the sponsor that trial enrolment should be stopped.

Clinical trial site:

Mitchells Plain Hospital and Khayelitsha Hospital

Details
Condition Disseminated Tuberculosis, HIV
Treatment prednisone, levofloxacin, Placebo, rifampin, Rifampicin, Pyrazinamide, Ethambutol and Isoniazid
Clinical Study IdentifierNCT04951986
SponsorUniversity of Cape Town
Last Modified on23 April 2022

Eligibility

Yes No Not Sure

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
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