Duong, Trinh;
Brigden, Joanna;
Simon Schaaf, H;
Garden, Frances;
Marais, Ben J;
Anh Nguyen, Thu;
White, Ian R;
... Fox, Greg J; + view all
(2025)
A Meta-Analysis of Levofloxacin for Contacts of Multidrug-Resistant Tuberculosis.
NEJM Evidence
, 4
(1)
10.1056/EVIDoa2400190.
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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.).
| Type: | Article |
|---|---|
| Title: | A Meta-Analysis of Levofloxacin for Contacts of Multidrug-Resistant Tuberculosis |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1056/EVIDoa2400190 |
| Publisher version: | https://doi.org/10.1056/evidoa2400190 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Levofloxacin, Humans, Tuberculosis, Multidrug-Resistant, Adult, Child, Antitubercular Agents, Middle Aged, Female, Male, Randomized Controlled Trials as Topic, South Africa, Vietnam, Child, Preschool |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10203055 |
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