#VisualAbstract: Non-severe TB in children can be treated with a shorter 4-month regimen instead of a 6-month regimen
- For children with non-severe tuberculosis, 4 months of anti-tuberculosis treatment was not less than 6 months of anti-tuberculosis treatment.
- For children with non-severe TB, a shorter treatment regimen did not significantly change the frequency of adverse events.
Evidence rating level: 1 (Excellent)
Summary of the study: Tuberculosis affects more than one million children each year with a mortality rate of around 20%. However, children usually have non-severe smear-negative TB compared to adults, but current guidelines recommend 6 months of TB treatment in children, the same duration as treatment in adults. Therefore, there is a knowledge gap to understand whether 4 months of TB treatment would be as effective as 6 months of treatment in children with non-severe, smear-negative, drug-susceptible TB. This study found that 4 months of anti-tuberculosis treatment was not inferior to 6 months of anti-tuberculosis treatment in children with non-severe tuberculosis. This study was limited by the fact that it was an open-label trial which may lead to more frequent treatment extensions in the four-month group, as well as generalizing the results to settings where chest radiographs are not available to characterize non-severe tuberculosis. Nevertheless, the results of this study are significant, as they demonstrate that 4 months of anti-tuberculosis treatment is effective in treating children with non-severe, drug-susceptible and smear-negative tuberculosis.
In depth [randomized control trial]: This open-label, non-inferiority, treatment-shortening trial studied 1204 children with non-severe, symptomatic tuberculosis in Uganda, Zambia, South Africa and India from July 2016 to July 2018. Patients under the age of 16-year-olds who had symptomatic, non-severe, smear-negative tuberculosis were included in the study. Non-severe tuberculosis was characterized as respiratory tuberculosis confined to one lobe with no cavities, no evidence of miliary tuberculosis, no complex pleural effusion, and no clinically significant airway obstruction. Patients not meeting these criteria were excluded from the study. Patients were either assigned to receive 4 months of anti-tuberculosis treatment or the standard 6 months of treatment using WHO recommended pediatric doses. The primary outcome was adverse status, consisting of treatment failure, switch, treatment restart, or recurrence of tuberculosis at 72 weeks. The primary safety endpoint was a grade 3 or higher adverse event during treatment and up to 30 days after treatment. The results of the primary analysis were conducted on modified intention-to-treat population protocols and log-rank tests and Cox proportional hazards models. Based on the analysis, non-inferiority through 4 months of anti-tuberculosis treatment was consistent across intention-to-treat, per-protocol and key secondary analyses. An unfavorable outcome was reported in 3% of the 4-month group and 3% in the 6-month group (95% confidence interval [CI], -2.3 to 1.6). There were no significant differences between the groups in the risks of an unfavorable condition (relative risk [HR], 0.88; 95% CI, 0.45 to 1.72) and no significant difference between groups in risk of death (RR, 0.63; 95% CI, 0.31 to 1.30). Additionally, 8% of participants had a grade 3 or higher adverse event, all but 2 of which occurred within the first 8 weeks when treatments were the same in both groups. Overall, this study demonstrated that 4 months of anti-tuberculosis treatment was non-inferior to 6 months of anti-tuberculosis treatment in children with non-severe tuberculosis in Africa and India. This encourages a stratified treatment approach to non-severe drug-susceptible tuberculosis in children.
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