Trial of High-Dose Rifampin in Patients With TB
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to evaluate the potential of high doses of rifampin (RIF) to
      shorten treatment for tuberculosis (TB) without causing more adverse events. The hypotheses
      are that higher doses of RIF will result in higher blood concentrations of RIF; higher blood
      concentrations will result in tuberculosis bugs being killed more quickly; and, both of these
      will happen without more adverse events. Patients with active, infectious, drug-susceptible
      TB who agree to participate will be randomly assigned to 1 of 3 doses of RIF. All patients
      will also receive standard doses of regular (3) companion drugs for 2 months of daily,
      supervised therapy. The study will assess the following among the 3 study arms (oral doses of
      RIF 10, 15 & 20 mg/kg/day) during the initial 8 weeks of treatment: 1) the amount of RIF in
      the blood after at least 14 days of treatment; 2) the difference in the number of
      tuberculosis bugs killed; 3) the frequency of adverse events.
    

Detailed description: 
      This is a Phase II, multi-site, dose-ranging trial comparing 3 doses of RIF in a multidrug
      regimen for treatment of smear-positive, pulmonary TB. The intervention phase of this
      prospective, randomized, double-blinded trial will last 8 weeks, the duration of the standard
      "intensive" phase for short-course chemotherapy for TB. During that time, subjects will
      receive the following companion drugs: isoniazid (INH, 5 mg/kg/day), ethambutol (EMB, 20
      mg/kg/day), and pyrazinamide (PZA, 25 mg/kg/day), pyridoxine (50 mg), the standard doses used
      in treatment. Subjects will also be randomized to receive one of the following weight-based
      doses of the study drug, rifampin (RIF): 10 mg/kg/day (standard dose, control), 15 mg/kg/day
      (intervention 1), 20 mg/kg/day (intervention 2). All patients will receive at least standard
      dose of RIF, the efficacy of which in multidrug-treatment for TB is well established. Placebo
      will be used to control only the additional RIF capsules provided in the intervention arms.
      Subjects, clinicians, and laboratory staff will be blinded to study arm. All patients in the
      same weight band will receive the same total number of tablets (fixed-dose combination plus
      RIF and/or placebo). Blinding is essential to reduce the probability of biased reporting of
      adverse events.

      After randomization, other covariates that may result in heterogeneity within strata (e.g.,
      presence of cavitation, HIV serostatus), will be adjusted for in analyses. It is important to
      maintain the ability to measure the effect (if any) of these potential characteristics on
      treatment outcome. If we were to stratify on these characteristics, we could not estimate
      their confounding (or interaction) effect. All doses will be delivered orally and fully
      supervised. All patients will receive weight-based doses of fixed-dose combinations according
      to package inserts. This will be supplemented by active RIF capsules or placebos, or both,
      according to weight and treatment arm. They will also all receive 50 mg of pyridoxine to
      prevent peripheral neuropathy, a common side effect of INH.
    

Intervention name(s): Higher-Dose Rifampin
Intervention type(s): Drug
Intervention description(s): The intervention phase of this trial will last 8 weeks. During that time, subjects will receive the following companion drugs: isoniazid (INH, 5 mg/kg/day), ethambutol (EMB, 20 mg/kg/day), and pyrazinamide (PZA, 25 mg/kg/day), pyridoxine (50 mg), the standard doses used in treatment. Subjects will also be randomized to receive one of the following weight-based doses of the study drug, rifampin (RIF): 10 mg/kg/day (standard dose, control), 15 mg/kg/day (intervention 1), 20 mg/kg/day (intervention 2). All patients will receive at least standard dose of RIF, the efficacy of which in multidrug-treatment for TB is well established. Placebo will be used to control only the additional RIF capsules provided in the intervention arms.
Other intervention name(s): rifadin, rifampicin
Intervention MeSH terms: Rifampin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment