Two-thirds of children with TB have non-severe disease that can be treated with a shorter regimen than the current six-month regimen
In a recent study published in the top medical journal NEJM, researchers conducted an open-label, shorter-duration, non-inferiority trial in Uganda, Zambia, South Africa, and India involving non-serious, symptomatic, potentially adverse effects.
Drug-susceptible children with smear-negative tuberculosis
Children under the age of 16 were randomly assigned to receive either 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis therapy using a fixed pediatric proportional-dose combination, as recommended by the World Health Organization
The primary efficacy outcome of the study was adverse status at 72 weeks (treatment failure [extending, changing or restarting treatment or TB relapse], loss to follow-up or death during treatment), excluding participants who did not complete 4 months of treatment (modified intent-to-treat population)
The researchers used a noninferiority margin of 6 percentage points
The primary safety outcome of the study was a grade 3 or higher adverse event during treatment and up to 30 days after treatment
From July 2016 to July 2018, a total of 1204 children in the study were randomized (602 in each group)
The median age of participants was 3.
5 years (range, 2 months to 15 years), 52% were male, 11% had HIV infection , and 14% had bacteriologically confirmed tuberculosis
Retention by 72 weeks was 95%, and adherence to assigned therapy was 94%
The primary outcome event occurred in 16 participants (3%) in the 4-month group and 18 (3%) in the 6-month group (adjusted difference -0.
4 percentage points; 95% confidence interval of -2.
2 to 1.
The non-inferiority of 4-month treatment was consistent across intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was limited to 958 participants (80%) who were independently adjudicated at baseline have tuberculosis
A total of 95 participants (8%) in the study had adverse events of grade 3 or higher, including 15 adverse drug reactions (11 hepatic events, all but 2 in the first 8 weeks )
Thus, for children with drug-sensitive, non-severe, smear-negative tuberculosis, 4-month anti-TB treatment was not inferior to 6-month treatment
Anna Turkova, et al.
Shorter Treatment for Nonsevere Tuberculosis in African and Indian Children .
Shorter Treatment for Nonsevere Tuberculosis in African and Indian Children