Levofloxacin versus placebo for the treatment of latent tuberculosis among contacts of patients with multidrug-resistant tuberculosis (the VQUIN MDR trial): a protocol for a randomised controlled trial

Abstract

IntroductionTreatment of latent tuberculosis infection (LTBI) plays a substantial role in the prevention of drug-susceptible tuberculosis (TB). However, clinical trials to evaluate the efficacy of preventive therapy for presumed multidrug-resistant (MDR) LTBI are lacking. This trial aims to evaluate the efficacy of the antibiotic levofloxacin in preventing the development of active TB among latently infected contacts of index patients with MDR-TB.Methods and analysisA double-blind placebo-controlled parallel group randomised controlled trial will be conducted in 10 provinces of Vietnam. Household contacts living with patients with bacteriologically confirmed rifampicin-resistant or MDR-TB will be eligible for recruitment if they have a positive tuberculin skin test or are known to be immunosuppressed, and do not have active TB. Participants will be randomised to receive either levofloxacin or placebo tablets once per day for 6 months. Screening for incident TB will be performed at 6 months intervals. The primary study outcome is the incidence of bacteriologically confirmed TB within 30 months after randomisation. Analysis will be by intention to treat, using Poisson regression.EthicsEthical approval from the University of Sydney Human Research Ethics Committee was obtained on 29 April 2015 (2014/929), and from the Vietnam Ministry of Health Institutional Review Board on 30 September 2015 (4040/QD-BYT).DisseminationFindings of the study will be published in peer-reviewed publications and conference presentations.Trial registration numberACTRN12616000215426.

Contact screening and management in a high-transmission MDR-TB setting in Papua New Guinea: Progress, challenges and future directions

“…Observational evidence from a number of settings suggests that a fluoroquinolone-based TPT regimen in MDR-TB contacts with evidence of TB infection (TBI) can substantially reduce the risk of developing MDR-TB, and with no significant safety concerns (22)(23)(24)(25)(26). The findings from two randomised-controlled trials of 6Lfx for MDR-TB contacts are expected in 2023 (27,28).…”

Anti-tuberculosis treatment strategies and drug development: challenges and priorities

“…Five regimens of various durations that include isoniazid and/or a rifamycin are recommended globally and considered equivalent by measure of effectiveness and hepatotoxicity, though they have not been directly compared in clinical trials 32 – 34 . Besides historic trials with pyrazinamide 35 , levofloxacin in children 36 and adults 37 , 38 and delamanid (PHOENIx MDR-TB) ( ClinicalTrials.gov , NCT03568383) are currently being tested as prophylactic therapy in household contacts of patients with MDR-TB.…”

Preventive Therapy for Contacts of Drug-Resistant Tuberculosis

“…The V-QUIN MDR-TB trial is a placebo-controlled, double-blind trial aiming to assess the role of levofloxacin in TPT for adult household contacts of MDR-TB patients (ACTRN12616000215426) [ 44 ]. The population of the trial, performed in Vietnam, included patients aged >15 years who were in contact with confirmed MDR-TB cases, during the prior three months and had a positive tuberculin skin test (TST).…”