Bedaquiline, pretomanid and linezolid for treatment of extensively drug resistant, intolerant or non-responsive multidrug resistant pulmonary tuberculosis

BACKGROUND: Patients with extensively drug resistant tuberculosis (TB) have limited treatment options with historically poor outcomes. We investigated treatment with 3 oral drugs, bedaquiline (B), pretomanid (Pa) and linezolid (L), (B-Pa-L), with TB bactericidal activity and little pre-existing resistance. METHODS: Nix-TB is an open label single arm study ongoing at three South African sites evaluating the safety and efficacy of B-Pa-L for 26 weeks for extensively drug-resistant TB or treatment intolerant /non-responsive multidrug-resistant TB. We present the efficacy and safety outcomes for all 109 patients enrolled in the trial followed to the predefined primary endpoint, six months after the end of treatment. RESULTS: In the intent to treat analysis, 98 patients (90%), (95% CI 82.7-94.9%) had a favourable outcome at 6 months after the end of treatment. Six patients died during the early stages of treatment, one withdrew during treatment, one died during follow-up without evidence of relapse, one relapsed, one relapsed and subsequently died during follow up and one was lost to follow-up. The expected linezolid toxicities of peripheral neuropathy (experienced by 81% of patients) and myelosuppression (48%), while common, were manageable, often requiring reductions of dose and/or interruptions in linezolid. CONCLUSIONS: These results suggest that B-Pa-L is a viable option for tuberculosis patients with highly resistant forms of TB, provided adequate safety management is available. Trial registration: ClinicalTrials.gov Identifier: NCT02333799 Sponsor: Global Alliance for TB Drug Development (TB Alliance)