Preventing drug-resistant tuberculosis TB in high-risk individuals, such as household contacts of patients with multidrug-resistant TB MDR-TB , is a global health priority. Out of individuals screened, were randomized, and TB developed in 6 participants. This difference was not statistically significant. Although grade 3 or 4 adverse events were similar between the two groups risk difference: 1 percentage point , adverse events of any grade were more common in the levofloxacin group Importantly, no acquired fluoroquinolone resistance was observed.
Importantly, it has lower cardiac toxicity compared to moxifloxacin, another fluoroquinolone, so we chose levofloxacin to avoid the need for cardiac monitoring. In this double-blind, randomized controlled trial, participants were randomized to receive either six months of daily levofloxacin or a placebo. The primary endpoint was bacteriologically confirmed TB within 30 months, while secondary endpoints included adverse events, mortality, and drug resistance.
Neither the participant nor the treating doctor knew which group they were in before or during treatment. This design helps reduce bias and ensures that any differences between the groups are due to the actual difference in the presence of the drug, not due to expectations. Although the V Quinn trial alone did not yield a statistically significant result due to lower-than-expected TB cases, Fox and his team combined the data with that from the TB Champ trial to increase statistical power.
So, before we analyzed the data from either trial, we pre-specified a combined analysis plan where we would merge the results. The combined analysis revealed a statistically significant reduction in TB incidence with levofloxacin, a result that was presented to the World Health Organization.
By pre-specifying the outcomes and conducting a combined analysis, we were able to confidently present our findings to the WHO. The treatment was associated with more adverse events, but no fluoroquinolone resistance emerged. These findings suggest that levofloxacin may not significantly reduce TB incidence in this high-risk population. The study underscores the need for further research into alternative prevention strategies for MDR-TB, particularly in settings where drug-resistant strains are prevalent.
