A Randomised Trial to Evaluate Toxicity and Efficacy of 1200mg and 1800mg Rifampicin for Pulmonary Tuberculosis
Condition: Pulmonary Tuberculosis
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Study type: Interventional
Phase: Phase 3

Summary: 
      In this trial, the investigators are assessing whether giving an increased dose of rifampicin
      to patients receiving the standard treatment for tuberculosis is safe and, when given for 4
      months only, will also result in greater and faster killing of the tubercle bacillus in the
      lungs and result in relapse rates similar to those found in the World Health Organisation
      (WHO) recommended standard 6 month regimen.
    

Detailed description: 
      Type of design An open-label 3-arm trial to compare a standard 6-month control regimen with
      two 4-month treatment regimens for the treatment of tuberculosis (TB).

      Disease/patients studied The trial will include 654 patients newly diagnosed with pulmonary
      TB with sputum positive or negative for TB on microscopy but with a positive result on a
      GeneXpert Test with organisms fully sensitive to rifampicin

      The treatment regimens - Control and Experimental

      Patients enrolled in the trial will be randomly allocated to receive one of the following
      three chemotherapy treatment regimens:

        1. Control regimen (R10): The standard regimen of isoniazid, pyrazinamide and ethambutol
           plus 10 mg/kg rifampicin for the initial 8 weeks, followed by isoniazid and rifampicin
           (at the same dose size) for an additional 4 months (2HRZE/4HR)A.

        2. Study regimen 1(SR1): 2 months of daily ethambutol, isoniazid, rifampicin, and
           pyrazinamide followed by 2 months of daily isoniazid and rifampicin. A supplement of
           either 450 mg (weight bands 35-39kg and 40-54kg) or 600mg (weight band 55-69kg and 70
           and more kg) of rifampicin will be given throughout the four months (2EHR
           1200Z/2HR1200)B.

        3. Study regimen 2(SR2): 2 months of daily ethambutol, isoniazid, rifampicin, and
           pyrazinamide followed by 2 months of daily isoniazid and rifampicin. A supplement of
           either 450 mg (weight bands 35-39kg and 40-54kg) or 600mg (weight band 55-69kg and 70
           and more kg) of rifampicin will be given throughout the four months
           (2EHR1800Z/2HR1800)C.

      1.1 Outcome measures Primary outcome measure

        1. Since the objective of the trial is to reduce treatment duration by increasing the dose
           of rifampicin, the primary outcome measure is the combined rate of failure at the end of
           treatment and relapse during the subsequent 12 months in smear positive patients.

        2. The occurrence of grade 3 or 4 adverse events at any time during chemotherapy.
    

Intervention name(s): Rifampicin; Isoniazid; Ethambutol; Pyrazinamide
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Rifampicin 150mg (Control arm); Rifampicin 1200mg (Regimen 1); Rifampicin 1800mg (Regimen 2); Isoniazid 75mg - all arms; Ethambutol 275mg - all arms; Pyrazinamide 400mg - all arms
Intervention MeSH terms: Rifampin; Isoniazid; Pyrazinamide; Ethambutol
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment