Despite reducing the median time to culture conversion, replacing ethambutol with moxifloxacin has not shown efficacy in recurrent tuberculosis treatment success in an 8-week trial, according to a study published in Clinical Infectious Diseases. Moxifloxacin use was also linked with more adverse events.
This open-label trial conducted at a single center in South Africa, included 196 individuals with tuberculosis, 69.9% of whom were men and 70.4% of whom had comorbid HIV. Random assignment stratified by HIV status to either intervention or control arms was performed in a 1:1 ratio with permuted block randomization. The study’s primary outcome was the rate of sputum culture conversion at the end of 8 weeks, which was defined as the first of 2 uninterrupted consecutive visits with negative cultures. Assessments were performed every 2 weeks during the study period and monthly for the 8-month follow-up. The Fisher’s Exact Test was used to analyze the primary outcome with Poisson regression used to improve estimates of treatment effect.
The moxifloxacin group did not significantly differ from controls in terms of culture conversion at the 8-week mark, with respective conversions among 83.0% (n=78) and 78.5% (n=73) of the 2 groups, respectively (P =.463). Culture conversion occurred in a significantly shorter time among the moxifloxacin group than the control group: 6.0 weeks (interquartile range [IQR], 4.0-8.3) vs 7.9 weeks (IQR, 4.0-11.4; P =.018). In addition, those in the moxifloxacin group with favorable treatment outcomes showed significantly shorter times to culture conversion (hazard ratio, 1.33; 95% CI, 0.98-1.80; P =.065).
The difference in favorable end-of-treatment outcomes was not statistically significant (absolute risk difference, -5.5%; 95% CI, -13.8% to 2.8%) with 87.8% (n=86) of participants in the moxifloxacin group attaining a favorable outcome and 94.9% (n=93) in the control group (P =.193). The most common cause of an unfavorable outcome were treatment failure and death, which occurred in 8 participants in the moxifloxacin group, and 3 in the control group. Adverse events of grades 3 or 4 were also higher in those given moxifloxacin (43.9% vs 25.5%; P =.011), as were serious adverse events (27.6% vs 12.2%; P =.012).
Limitations to this study included a small sample size due to slow recruitment, as well as a shortened follow-up period.
The researchers concluded that “the substitution of ethambutol with moxifloxacin for the treatment of recurrent pulmonary tuberculosis did not improve treatment success in comparison to the standard regimen, despite a shorter median duration to culture conversion.” However, researchers noted that participants, particularly those with comorbid HIV, in the moxifloxacin group has a significantly shorter median time to culture conversion, which suggested that moxifloxacin me be a useful therapeutic option to reduce transmission in people with TB/HIV coinfection.
This study was funded by the European and Developing Countries Clinical Trials Partnership.
Perumal R, Padayatchi N, Yende-Zuma N, Naidoo A, Govender D, Naidoo K. A moxifloxacin-based regimen for the treatment of recurrent drug-sensitive pulmonary tuberculosis: an open-label randomised controlled trial [published online February 27, 2019]. Clin Infect Dis. doi: 10.1093/cid/ciz152