1. The current standard regimen for tuberculosis treatment involves 6 months of antibiotic therapy with isoniazid, rifampin, pyrazinamide, and ethambutol.
2. This trial failed to demonstrate non-inferiority of four-month regimens, with moxifloxacin replacing one of the drugs in the standard regimen, compared to the standard regimen.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Tuberculosis (TB) remains one of the most common and lethal infectious diseases worldwide, associated with approximately 2 million deaths per year. The current standard regimen for treating TB involves 6 months of antibiotic therapy which can be costly and presents challenges with respect to medication compliance. Fluoroquinolones, already an important component of multidrug-resistant TB therapy, have shown promise in reducing the duration of treatment and thereby increasing adherence to treatment regimens. Several studies have demonstrated that moxifloxacin-containing regimens lead to more rapid reductions in bacterial load. Moreover, moxifloxacin-containing regimens achieved clinical cure without relapse with far shorter treatment duration compared to standard therapy in murine models. The purpose of the Rapid Evaluation of Moxifloxacin in Tuberculosis (REMoxTB) trial was to explore whether replacing isoniazid or ethambutol in the standard 6-month regimen with moxifloxacin would provide effective TB treatment in 4 months of therapy.
In summary, while the two moxifloxacin-containing regimens led to significantly faster reductions in bacterial load, this trial did not demonstrate non-inferiority compared to the standard regimen in achieving favorable outcomes.
Relevant Reading: Tuberculosis
In-Depth [randomized controlled trial]: This phase 3, randomized, controlled study sought to determine whether two moxifloxacin-containing 4-month regimens were non-inferior to the standard 6 month regimens currently used for TB treatment. Eligible patients were at least 18 years of age, had newly diagnosed and previously untreated Mycobacterium tuberculosis infection, demonstrated by two positive results on sputum smears and culture-confirmed susceptibility to rifampin and fluoroquinolones. Patients with human immunodeficiency virus (HIV) were included in the study if their CD4+ counts exceeded 250 cells/mm3 and they were not already being treated with antiretrovirals. Eligible patients were randomized in a 1:1:1 ratio to three different treatment arms: 1) the control regimen (i.e., isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, then isoniazid and rifampin for another 18 weeks), 2) the isoniazid group (i.e., a regimen where ethambutol was replaced with moxifloxacin for 17 weeks, followed by 9 weeks of placebo), and 3) the ethambutol group (i.e., a regimen where isoniazid was replaced with moxifloxacin for 17 weeks, followed by 9 weeks of placebo). The primary outcome was the proportion of patients with bacteriologically or clinically defined failure/relapse in the first 18 months after randomization.
A total of 1,931 patients were randomized for this trial. Treatment adherence (i.e., receipt of approximately 80% of the regimen) was 89%, 89%, and 92% in the control, isoniazid, and ethambutol groups, respectively. In the per-protocol analysis, 85% of patients in the isoniazid group and 92% of patients in the control group had a favourable outcome (adjusted absolute difference, 6.1%; 97.5% CI, 1.7-10.5). Approximately 80% of patients in the ethambutol group experienced a favourable outcome (adjusted absolute difference, 11.4%; 97.5% CI, 6.7-16.1; favouring control group). Similar results were seen in the modified intention-to-treat analysis. Patients in the isoniazid and ethambutol groups converted to culture-negative status sooner than those in the control group (p<0.01 for both comparisons). There were no significant differences between groups in the rates of adverse events.
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