Trial Information

A Randomised Placebo - Controlled Double Blind Trial Comparing 1) a Two Month Intensive Phase of Ethambutol, Moxifloxacin, Rifampicin, Pyrazinamide Versus the Standard Regimen (Ethambutol, Isoniazid, Rifampicin, Pyrazinamide) and 2) a Treatment Shortening Regimen Comparing Two Months Moxifloxacin, Isoniazid, Rifampicin, Pyrazinamide Followed by Two Months Moxifloxacin, Isoniazid, Rifampicin Versus the Standard Regimen (Two Months Ethambutol, Isoniazid, Rifampicin, Pyrazinamide Followed by Four Months Isoniazid and Rifampicin) for the Treatment of Adults With Pulmonary Tuberculosis

The current recommended treatments for tuberculosis (TB) require a patient to take multiple
drugs for six to eight months. Because the course of therapy is long, many patients do not
adhere to treatment and as a consequence they have a poor outcome. In these cases either
the sputum is not cleared of the bacteria causing tuberculosis, or the disease returns again
(called relapse). Response to medication can be monitored during treatment by collecting
regular sputum samples and examining these samples by culture, for the organisms that cause
tuberculosis.

The commonly used drugs to treat tuberculosis are rifampicin, isoniazid, ethambutol and
pyrazinamide. Previous studies in animals and in humans suggest that a new drug called
moxifloxacin may also be an effective treatment in tuberculosis. Moreover, promising
laboratory studies on mice suggest that moxifloxacin may enable the total duration of
chemotherapy to be reduced to four months, which would be a significant improvement for
patients taking medication for tuberculosis.

This study will involve comparisons that are designed to assess whether substituting
moxifloxacin for individual drugs in existing treatment combinations will enable
tuberculosis treatment to be shortened. Patients selected for the study will be allocated
to one of three treatment groups. The first group will be given six months standard
treatment. A second group will receive moxifloxacin substituted for ethambutol, as part of
a four month regimen, to see whether the shorter treatment is not inferior to the standard
six month treatment. The third group will receive moxifloxacin substituted for isoniazid,
as part of a four month regimen, to see whether the shorter treatment is not inferior to the
standard six month treatment.

Hypotheses:

1. In treatment-naïve adults with active pulmonary TB treated with eight weeks of
moxifloxacin (M), isoniazid (H), rifampicin (R) and pyrazinamide (Z) (i.e. a standard
regimen where moxifloxacin is substituted for ethambutol (E)), followed by nine weeks
of moxifloxacin, isoniazid and rifampicin, followed by nine weeks of placebo, the
proportion of patients who experience treatment failure or disease relapse in the
twelve months following treatment completion will not be inferior to that observed in
patients who are treated with a standard regimen (eight weeks of ethambutol, isoniazid,
rifampicin and pyrazinamide followed by eighteen weeks of isoniazid plus rifampicin)
(Comparison 1).

2. In treatment-naïve adults with active pulmonary TB treated with eight weeks of
ethambutol, moxifloxacin, rifampicin and pyrazinamide (i.e. a standard regimen where
moxifloxacin is substituted for isoniazid), followed by nine weeks of moxifloxacin and
rifampicin followed by nine weeks of placebo, the proportion of patients who experience
treatment failure or disease relapse in the twelve months following treatment
completion will not be inferior to that observed in patients who are treated with a
standard regimen (eight weeks of ethambutol, isoniazid, rifampicin and pyrazinamide
followed by eighteen weeks of isoniazid plus rifampicin) (Comparison 2).