1. Patients with pulmonary tuberculosis receiving a shortened, 4-month treatment regimen with gatifloxacin were more likely to experience an unfavourable outcome at 24 months than patients receiving the standard 6-month regimen.
2. Patients in the experimental group were less likely to have treatment failure but were more likely to have a recurrence of tuberculosis than those receiving standard therapy,
Evidence Rating Level: 1 (Excellent)
Study Rundown: Although the incidence and mortality rates of tuberculosis peaked a decade ago, the disease remains a public health challenge. Millions of individuals are still affected each year and the incidence of multi-drug resistant tuberculosis (MDR-TB) is rising, as a result of failure to complete treatment course or inappropriate use of drug therapies. The standard treatment of tuberculosis requires 6 months of multiple antimicrobial medications. Fluoroquinolones have shown promise in shortening the duration of treatment and have been investigated in attempts to improve treatment adherence.
This phase 3 trial randomized patients to a 4-month treatment regimen with the fluoroquinolone, gatifloxacin, or the standard 6-month regimen using ethambutol during the initial phase of management. The study was unable to show noninferiority of a 4-month regimen with gatifloxacin compared to the standard 6-month regimen. It is possible that drug levels were insufficient to demonstrate the true effect of the experimental regimen since a standard dose of gatifloxacin was given without adjustment according to body weight. Overall, the use of a composite outcome that included outcomes of varying severity made the findings difficult to interpret. Although promising in phase 2 trials, shortened fluoroquinolone-containing treatment regimens have failed to show noninferiority compared to the standard regimen thus far.
Relevant Reading: Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis
In-Depth [randomized controlled trial]: This phase 3, open-label, randomized controlled trial included 1836 patients with smear-positive, rifampin-sensitive pulmonary tuberculosis in 5 countries in sub-Saharan Africa. Patients were randomized to a standard 6-month regimen including a 2-month intensive treatment phase with ethambutol, or the experimental 4-month regimen substituting 400 mg gatifloxacin per day for ethambutol during the intensive phase and continued for the duration of treatment. The primary outcome was a composite of treatment failure, recurrence, death, or study dropout, measured at 24 months after the end of treatment.
Modified intention-to-treat analysis of the primary outcome in 1356 patients showed a risk difference of 3.5 percentage points (experimental group minus control group; 95% CI, -0.7 to 7.7). The per-protocol analysis demonstrated an adjusted difference of 5.5 percentage points (experimental group minus control group; 95% CI, 1.6 to 9.4). Treatment failure occurred more frequently in the control group compared to the experimental group (2.4% vs. 1.7%); however, more patients in the experimental group had a recurrence of tuberculosis (14.6% vs. 7.1%).
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