A meta-analysis of levofloxacin for contacts of multidrug-resistant TB
File(s)
Author(s)
Type
Journal Article
Abstract
Background
Data from randomized trials evaluating the effectiveness of tuberculosis (TB) preventive treatment for contacts of multidrug-resistant (MDR)-TB are lacking. Two recently published randomized trials that did not achieve statistical significance provide the opportunity for a meta-analysis.
Methods
We conducted combined analyses of two phase 3 trials of levofloxacin MDR-TB preventive treatment — Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis (VQUIN) trial and the Levofloxacin preventive treatment in children exposed to MDR-TB (TB-CHAMP) trial. Following MDR-TB household exposure, VQUIN enrolled mainly adults in Vietnam; TB-CHAMP enrolled mainly young children in South Africa. Random assignment in both trials was 1:1 at the household level to daily levofloxacin or placebo for 6 months. The primary outcome was incident TB by 54 weeks. We estimated the treatment effect overall using individual participant data meta-analysis.
Results
The VQUIN trial (n=2041) randomly assigned 1023 participants to levofloxacin and 1018 participants to placebo; TB-CHAMP (n=922) assigned 453 participants to levofloxacin and 469 participants to placebo. Median age was 40 years (interquartile range 28 to 52 years) in VQUIN and 2.8 years (interquartile range 1.3 to 4.2 years) in TB-CHAMP. Overall, 8 levofloxacin-group participants developed TB by 54 weeks versus 21 placebo-group participants; the relative difference in cumulative incidence was 0.41 (95% confidence interval [CI] 0.18 to 0.92; P=0.03). No association was observed between levofloxacin and grade 3 or above adverse events (risk ratio 1.07, 95% CI 0.70 to 1.65). Musculoskeletal events of any grade occurred more frequently in the levofloxacin group (risk ratio 6.36, 95% CI 4.30 to 9.42), but not among children under 10 years of age. Overall, four levofloxacin-group participants and three placebo-group participants had grade 3 events.
Conclusions
In this meta-analysis of two randomized trials, levofloxacin was associated with a 60% relative reduction in TB incidence among adult and child household MDR-TB contacts, but with an increased risk of musculoskeletal adverse events. (Funded by the Australian National Health and Medical Research Council, UNITAID, and others.)
Data from randomized trials evaluating the effectiveness of tuberculosis (TB) preventive treatment for contacts of multidrug-resistant (MDR)-TB are lacking. Two recently published randomized trials that did not achieve statistical significance provide the opportunity for a meta-analysis.
Methods
We conducted combined analyses of two phase 3 trials of levofloxacin MDR-TB preventive treatment — Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis (VQUIN) trial and the Levofloxacin preventive treatment in children exposed to MDR-TB (TB-CHAMP) trial. Following MDR-TB household exposure, VQUIN enrolled mainly adults in Vietnam; TB-CHAMP enrolled mainly young children in South Africa. Random assignment in both trials was 1:1 at the household level to daily levofloxacin or placebo for 6 months. The primary outcome was incident TB by 54 weeks. We estimated the treatment effect overall using individual participant data meta-analysis.
Results
The VQUIN trial (n=2041) randomly assigned 1023 participants to levofloxacin and 1018 participants to placebo; TB-CHAMP (n=922) assigned 453 participants to levofloxacin and 469 participants to placebo. Median age was 40 years (interquartile range 28 to 52 years) in VQUIN and 2.8 years (interquartile range 1.3 to 4.2 years) in TB-CHAMP. Overall, 8 levofloxacin-group participants developed TB by 54 weeks versus 21 placebo-group participants; the relative difference in cumulative incidence was 0.41 (95% confidence interval [CI] 0.18 to 0.92; P=0.03). No association was observed between levofloxacin and grade 3 or above adverse events (risk ratio 1.07, 95% CI 0.70 to 1.65). Musculoskeletal events of any grade occurred more frequently in the levofloxacin group (risk ratio 6.36, 95% CI 4.30 to 9.42), but not among children under 10 years of age. Overall, four levofloxacin-group participants and three placebo-group participants had grade 3 events.
Conclusions
In this meta-analysis of two randomized trials, levofloxacin was associated with a 60% relative reduction in TB incidence among adult and child household MDR-TB contacts, but with an increased risk of musculoskeletal adverse events. (Funded by the Australian National Health and Medical Research Council, UNITAID, and others.)
Date Issued
2025-01-01
Date Acceptance
2024-11-20
Citation
NEJM Evidence, 2025, 4 (1)
ISSN
2766-5526
Publisher
Massachusetts Medical Society
Journal / Book Title
NEJM Evidence
Volume
4
Issue
1
Copyright Statement
Copyright © 2025 Massachusetts Medical Society. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Identifier
https://evidence.nejm.org/doi/10.1056/EVIDoa2400190
Publication Status
Published
Date Publish Online
2024-12-18