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

Prior treatment

• Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial.
• Angina pectoris requiring treatment with nitroglycerin or other nitrates
• Patients requiring treatment with medications not compatible with rifampin, such as HIV protease inhibitors

Other illness

• 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, such as pneumothorax or clinically significant pleural effusion
• TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator.
• History of allergy or hypersensitivity to any of the trial therapies or related substances, including known allergy or suspected hypersensitivity to rifampin.
• Cardiac arrhythmia requiring medication, or any clinically significant ECG abnormality, in the opinion of the investigator
• Use of systemic corticosteroids within the past 28 days, or a likely to require corticosteroids for management of another medical condition during the period of study participation.

Lab values

• Random blood glucose \>140 mg/dL (or \>7.8 mmol/L), or history of unstable Diabetes Mellitus which required hospitalization for hyper- or hypoglycaemia within the past year prior to start of screening.
• Subjects with any of the following abnormal laboratory values:
  • creatinine \>2 mg/dL
  • haemoglobin \<8 g/dL
  • platelets \<100x109 cells/L
  • serum potassium \<3.5
  • aspartate aminotransferase (AST) ≥2.0 x ULN
  • alkaline phosphatase (AP) \>5.0 x ULN
  • total bilirubin \>1.5 mg/dL
  • positive HBsAg

Other

• Pregnancy or breast-feeding
• 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.
• No more than 5 days treatment for the current TB episode, and no other TB treatment in the preceding 6 months

• Persons aged 18 to 65 years
• Willing and able to provide signed written consent, or witnessed oral con-sent with thumbprint in the case of illiteracy, prior to undertaking any trial-related procedures.
• Body weight (in light clothing without shoes) between 30 and 90 kg.
• Xpert TB/RIF OR Ultra showing RIF-S-MTB, with subsequent confirmation of MTB by culture.
• Chest radiograph meeting criteria for moderate or far advanced pulmonary tuberculosis 1
• FEV1 ≤65% of predicted adjusted for age, height, sex, and race
• If female, of child-bearing potential and sexually active, willing to use a contraceptive method for the duration of study participation
• HIV-1/2 seronegative, or if seropositive: CD4 T cell count ≥100/mcL and either currently receiving ART or willing to start ART during study participation