A Confirmatory Trial of Adjunctive NAC to Prevent Post Tuberculosis Lung Disease

Inclusion Criteria:

1. Persons aged 18 to 65 years

2. Willing and able to provide signed written consent, or witnessed oral con-sent withthumbprint in the case of illiteracy, prior to undertaking any trial-relatedprocedures.

3. Body weight (in light clothing without shoes) between 30 and 90 kg.

4. Xpert TB/RIF OR Ultra showing RIF-S-MTB, with subsequent confirmation of MTB byculture.

5. Chest radiograph meeting criteria for moderate or far advanced pulmonarytuberculosis 1

6. FEV1 ≤65% of predicted adjusted for age, height, sex, and race

7. If female, of child-bearing potential and sexually active, willing to use acontraceptive method for the duration of study participation

8. HIV-1/2 seronegative, or if seropositive: CD4 T cell count ≥100/mcL and eithercurrently receiving ART or willing to start ART during study participation

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 confoundprotocol specified assessments, such as pneumothorax or clinically significantpleural effusion

2. Pregnancy or breast-feeding

3. Is critically ill, and in the judgment of the investigator has a diagnosis likely toresult in death during the trial or the follow-up period.

4. TB meningitis or other forms of severe tuberculosis with high risk of a poor outcomeas judged by the investigator.

5. History of allergy or hypersensitivity to any of the trial therapies or relatedsubstances, including known allergy or suspected hypersensitivity to rifampin.

6. Having participated in other clinical trials with investigational agents within 8weeks prior to trial start or currently enrolled in an investigational trial.

7. No more than 5 days treatment for the current TB episode, and no other TB treatmentin the preceding 6 months

8. Angina pectoris requiring treatment with nitroglycerin or other nitrates

9. Cardiac arrhythmia requiring medication, or any clinically significant ECGabnormality, in the opinion of the investigator

10. Random blood glucose >140 mg/dL (or >7.8 mmol/L), or history of unstable DiabetesMellitus which required hospitalization for hyper- or hypoglycaemia within the pastyear prior to start of screening.

11. Use of systemic corticosteroids within the past 28 days, or a likely to requirecorticosteroids for management of another medical condition during the period ofstudy participation.

12. Patients requiring treatment with medications not compatible with rifampin, such asHIV protease inhibitors

13. Subjects with any of the following abnormal laboratory values:

14. creatinine >2 mg/dL

15. haemoglobin <8 g/dL

16. platelets <100x109 cells/L

17. serum potassium <3.5

18. aspartate aminotransferase (AST) ≥2.0 x ULN

19. alkaline phosphatase (AP) >5.0 x ULN

20. total bilirubin >1.5 mg/dL

21. positive HBsAg