A Meta-Analysis of Levofloxacin for Contacts of Multidrug-Resistant Tuberculosis

作者：Trinh Duong, Joanna Brigden, H. Simon Schaaf, Frances Garden, Ben J. Marais, Thu Anh Nguyen, Ian R. White, Diana M. Gibb, Nguyen Viet Nhung, Neil Martinson, Lee Fairlie, Leonardo Martínez, Charlotte Layton, Andrea Benedetti, Guy B. Marks, Rebecca Turner, James A. Seddon, Anneke C Hesseling, Greg J. Fox · 发表于：NEJM Evidence · 年份：2024 · DOI：10.1056/evidoa2400190 · 被引用次数：39 · 研究领域：Tuberculosis Research and Epidemiology、Infectious Diseases and Tuberculosis、Pharmaceutical studies and practices

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 interv...