Efficacy and Tolerability of Delamanid, Linezolid, Pyrazinamide and Levofloxacin

Summary

The proposed study will randomize adults (18 years of age or older) with pulmonary MDR-TB with sputum that contains M. tuberculosis that is isoniazid and rifampin resistant by MTBDRplus and fluoroquinolone susceptible by MTBDRsl HIV seropositive (with or without antiretroviral therapy) or negative (but not unknown) and Karnofsky score of \>60 at sites in Moldova, Peru, and the Philippines. Patients with MDR-TB will be randomized to oral regimen of delamanid (DLM), linezolid (LZD), levofloxacin (LFX) and pyrazinamide (PZA) for 24, 32, 40, 48 or 56 weeks or World Health Organization (WHO) standard of care MDR-TB regimen (9-month "modified Bangladesh" regimen or WHO standard MDR-TB regimen). Primary Objective 1\. Determine the shortest duration of the delamanid-containing oral regimen that is non-inferior to the blended WHO standard regimen. Secondary Objective 1. Define the safety and tolerability of the oral delamanid, linezolid, levofloxacin and pyrazinamide regimen. 2. Determine if baseline PZA susceptibility is associated with shorter time to non-inferior treatment duration. 3. Identify the relationship between delamanid and linezolid serum drug levels and time to sputum culture conversion among patients on the delamanid-containing oral regimen. 4. Identify the relationship between delamanid and linezolid serum drug levels and occurrence of adverse events among patients on the delamanid-containing oral regimen.

Timeline

Start

2017-08

Primary completion

2021-08

Completion

2022-08

Drugs

Indications