Abstract
BACKGROUND: WHO recommends all-oral bedaquiline (BDQ) and linezolid (LZD)-containing regimens for rifampicin-resistant TB (RR-TB). In Niger, high cure rates were achieved using an adaptive short treatment regimen (aSTR) with a second-line injectable drug (SLID) and LZD, where LZD replaced the SLID in case of any ototoxicity detected on monthly audiometry. In 2020, WHO recommended a short oral BDQ/LZD regimen (oSTR). However, the success reported for oSTR was lower than for aSTR in Niger. The 'SHOrt ORal Treatment' trial therefore compared the safety and efficacy between aSTR and oSTR in Niger. METHODS: In this pragmatic clinical trial, patients with fluoroquinolone-susceptible RR-TB were assigned by alternate months to aSTR or oSTR. Regression models estimated the association between regimen and safety (grade 3-4 adverse events [AEs]) and efficacy (excluding loss to follow-up). RESULTS: Between 2021-2022, 158 RR-TB patients were included, 80 on oSTR and 78 on aSTR. Overall, 34 patients experienced 43 grade 3-4 AEs (anaemia: 15, neurotoxicity: 11, vomiting: 8, hepatitis: 7, arthralgia: 1, QTc prolongation: 1). Grade 3-4 AEs occurred in 26/80 (32.5 %) on oSTR versus 8/78 (10.3%) on aSTR, with anaemia, neurotoxicity and arthralgia being significantly higher in the oSTR group. Ototoxicity and nephrotoxicity appeared more frequently during the aSTR, but none evolved to grade 3. Patients treated with oSTR had a 3-fold increase in grade 3-4 AE (aHR 3.04;95% CI:1.36-6.80). End-of-treatment success was similar for oSTR compared to aSTR. CONCLUSION: aSTR was safer than oSTR and both approaches had a similar treatment efficacy.