Tuberculosis
Conditions
Interventions
Sutezolid 1200mg QD plus bedaquiline and pretomanid
Sutezolid 1600mg QD plus bedaquiline and pretomanid
Sutezolid 1600mg QD plus bedaquiline pretomanid and N acetyl cysteine
2HRZE and 4HR
Sponsors
The Aurum Institue NPC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 18 to 65 years 2. Willing and able to provide signed written consent prior to undertaking any trial-related procedures. a. Or, in the case of illiteracy, witnessed oral consent 3. Body weight (in light clothing without shoes) between 30 and 90 kg. 4. Radiographic evidence of pulmonary tuberculosis 5. Positive Xpert TB/RIF (original or Ultra) for MTB 6. RIF susceptibility diagnosed by Xpert TB/RIF, with subsequent culture confirmation 7. If sexually active, willing to use an effective contraceptive method for the duration of tuberculosis treatment 8. HIV-1 seronegative, or if HIV-1 seropositive, CD4 T cell count =100/µl and either receiving ART or willing to start ART during study participation 9. SARS-CoV-2 PCR or antigen test negative, or if positive, either fully vaccinated against Covid-19 or with D-dimer <0.8 ?g/ml 10. Willing to adhere to a diet excluding tyramine-rich foods (certain mold-ripened cheeses and cured meats), and to avoid eating grapefruits and pomelos
Exclusion criteria
Exclusion criteria: 1. Any condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments 2. Current or imminent (within 24 hr) treatment for malaria. 3. Pregnant or nursing 4. Is critically ill, and in the judgment of the investigator has a diagnosis likely to result in death during the trial or the follow-up period. 5. TB meningitis or spondylitis, or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator. 6. History of allergy or hypersensitivity to any of the trial therapies or related substances. 7. Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial. 8. Prior TB treatment in the preceding 6 months 9. Angina pectoris requiring treatment with nitroglycerin or other nitrates 10. Cardiac arrhythmia requiring medication, or any clinically significant ECG abnormality, in the opinion of the investigator 11. History of unstable Diabetes Mellitus requiring hospitalization for hyper- or hypo-glycaemia within the past year prior to start of screening. 12. Use of systemic corticosteroids within the past 28 days. 13. Patients requiring treatment with medications not compatible with rifampin, such as HIV-1 protease inhibitors 14. Patients requiring treatment with antidepressants, including MAO inhibitors and SSRIs. 15. Subjects with any of the following abnormal laboratory values: a. HBsAg positive b. creatinine >2 mg/dL c. hemoglobin 5.0 x ULN h. total bilirubin >1.5 mg/dL i. random blood glucose >200 mg/dL NB: All of the inclusion and none of the exclusion criteria must be met
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of patients achieving durable (non-relapsing) cure, assessed after 1 year of post-treatment follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety 1. The proportion of subjects with TE ALT increases, graded according to severity 2. The proportion of subjects with TE increases in transaminases and bilirubin meeting Hy’s criteria for se-rious liver injury 3. The proportion of subjects with TE AEs, according to seriousness 4. The number of TE AEs per treatment arm, according to seriousness 5. The proportion of subjects requiring temporary or permanent treatment discontinuation due to safety or tolerability concerns ;Pulmonary function 6. FEV1 and FVC at 1, 2, 6, and 18 months after initiation of treatment 7. FEV1 and FVC slope during 6 and 18 months after initiation of treatment 8. FEV1/FVC ratio at 1, 2, 6, and 18 months after initiation of treatment ;Microbiology 9. The proportion of subjects with sputum cultures showing growth of MTB at 1, 2, 3, and 4 months after initiation of treatment 10. The hazard ratio for stable culture conversion through the 4th month of treatment 11. The proportion of subjects with treatment failure 12. The proportion of subjects with relapse | — |
Countries
Mozambique, South Africa, United Republic of Tanzania
Contacts
Public ContactDon Mudzengi
Programme Manager
Outcome results
None listed