A Short Regimen for Rifampicin-resistant Isoniazid-susceptible TB

Prior treatment

• Is unable to take oral medication
• Is taking any medications contraindicated with the medicines in either the trial or control regimen
• Is currently taking part in another trial of a medicinal product

Other illness

• Is infected with a strain of M. Tuberculosis resistant to isoniazid by Xpert MTB/XDR or other tests
• Is infected with a strain of M. Tuberculosis resistant to fluoroquinolone by Xpert MTB/XDR or other tests
• Is infected with a strain of M. Tuberculosis resistant to amikacin by Xpert MTB/XDR or other tests and have no result of susceptibility of isoniazid by conventional drug susceptibility testing
• Has tuberculous meningitis or bone and joint tuberculosis
• Has any condition (social or medical) which in the opinion of the investigator would make study participation unsafe.
• Has a known allergy to any fluoroquinolone antibiotic

Lab values

• Has AST or ALT \>5 times the upper limit of normal
• Has AST or ALT \> 3 times the upper limit of normal ,and either with symptoms of hepatitis or bilirubin \> 1.5 times the upper limit of normal

Other

• A patient will not be eligible for entry to the study if he/she:
• Is critically ill, and in the judgment of the investigator, unlikely to survive more than 4 months.
• Is known to be pregnant or breast-feeding
• Is unable to attend or comply with treatment or follow-up schedule
• Has a QTcF interval of ≥450msec at screening

• A patient will be eligible for entry to the study if he/she:
• Is willing and able to give informed consent to be enrolled in the trial treatment and follow-up (signed or witnessed consent if the patient is illiterate)
• Is aged 18 years or older
• Has bacteriologically-confirmed pulmonary tuberculosis by Xpert MTB/RIF, other nucleic acid amplification test, or culture
• With initial laboratory result of resistance to rifampicin by Xpert MTB/RIF or Xpert MTB/RIF ultra, or other DST (line probe assay, culture); and with initial laboratory result that is susceptible to isoniazid by Xpert MTB/RIF or other DST. If rifampicin resistance is detected by Xpert MTB/RIF or Xpert MTB/RIF ultra in specimens with very low bacillary, rifampicin resistance has been confirmed by a repeat molecular test.
• With initial laboratory result of being susceptible to rifampicin by Xpert MTB/RIF or other DST (Xpert MTB/RIF ultra, line probe assay, culture) but are not able to tolerate rifampicin for whom rifabutin is intolerable or clinically not indicated; and with initial laboratory result that is susceptible to isoniazid by Xpert MTB/RIF or other DST
• With initial laboratory result of being susceptible to rifampicin by Xpert MTB/RIF or other DST (Xpert MTB/RIF ultra, line probe assay, culture) but rifamycin-sparing regimens are preferred due to drug-drug interaction, such as organ transplant recipients; and with initial laboratory result that is susceptible to isoniazid by Xpert MTB/RIF or other DST.
• With initial laboratory result that is susceptible to fluoroquinolone by Xpert MTB/XDR or other DST.
• If HIV test positive, is willing to be treated with ART in accordance with the national policies.
• Agrees to use effective barrier contraception or have an intrauterine contraceptive device during treatment phase if a pre-menopausal woman
• Has an identifiable address and expects to remain in the area for the duration of the study
• Is willing to adhere to the follow-up schedule and to study procedures