Evaluating the effectiveness of a fluoroquinolone-based treatment of isoniazid-resistant tuberculosis: The FLIRT Trial

Tuberculosis (TB) kills over 1.4 million people each year and has been the top infectious cause of death worldwide since 2015. Drug resistance is a major driver of prolonged morbidity and mortality, contributing to poor outcomes and allowing ongoing transmission of this airborne infection. Drug-resistant TB is caused by Mycobacterium tuberculosis that is resistant to at least one of the four first-line antibiotics used in combination to treat TB (isoniazid [INH], rifampicin [RIF], pyrazinamide [PZA] or ethambutol [EMB]). No trials of INH-resistant (INH-R) TB have been performed since the availability of later-generation fluoroquinolones (FQs), one of the best-tolerated and most effective group of antibiotics against TB. Safer and more effective regimens are needed. WHO called for treatment trials for INH-R TB, yet none are planned based upon our review of trial registries. The study hypothesis is that six months of an antibiotic treatment that includes a fluoroquinolone antibiotic will improve treatment outcomes for patients with isoniazid-resitsant tuberculosis. The research question to be addressed by this trial is: “What is the effectiveness and safety of a 6-month fluoroquinolone-containing intervention regimen, with 2 months of pyrazinamide, in comparison to that of a control regimen not containing a fluoroquinolone for treatment of isoniazid-resistant fluoroquinolone resistant tuberculosis?”