Shorter and Safer Treatment Regimens for Latent TB

Prior treatment

• Current tuberculosis (TB) disease - detected pre-enrolment with symptom screen, chest x-ray, and confirmatory microbiological (culture or genotypic) testing as needed; Prior to referral to research staff (research clinic) for consideration as potential participants, all persons must undergo symptoms screen and a chest Xray. If chest Xray is not available, then a negative results from a GeneXpert MTb RIF Ultra of spontaneous (expectorated) sputum will be considered sufficient to exclude TB disease pre-referral. If Chest Xray is abnormal or symptoms consistent with TB disease are present then at least two AFB smears and mycobacterial cultures must be done, and must be negative, or one GeneXpert MTb Rif Ultra must be negative before enrolment
• Documented prior treatment for tuberculosis (TB) infection or disease;

Other illness

• Rifampin or rifapentine contra-indicated - due to allergy/hypersensitivity to any rifamycin (rifampin, rifabutin or rifapentine), or, drug interactions too difficult to manage;
• Household contacts (HHC) of index TB patients with phenotypic or genotypic resistance to Rifampin or Levofloxacin. HHC may be enrolled, then excluded post-randomization, if resistance is identified later. Note that all sites routinely test Rifampin resistance in all people newly diagnosed to have TB disease, but do not test routinely for susceptibility to Levofloxacin unless Rifampin resistance is detected. Hence HHCs may be enrolled if their Index TB patient is Rifampin susceptible, even if Drug Susceptibility Testing to Levofloxacin is not done and/or not available.

Lab values

• Pre-enrolment - alanine transaminase (ALT), White Blood Cells, platelets or hemoglobin that correspond to a Grade 3 adverse event (AE);
• Have a prolonged QT interval on routine ECG pre-enrolment or take any medications that may prolong the QT interval and that are not recommended to take with a fluroquinolone. (See APPENDIX 5 in supplement for list of medications contra-indicated to take with Levofloxacin);

Age

• Children aged 0-4 years;

Other

• Persons weighing \<15 kg.
• Women who are pregnant or breast-feeding;
• Women of child-bearing potential and not willing to take an effective form of contraception (non-hormonal) during the treatment phase;

• Adults, and children aged ≥5 years with weight of \> 15Kg.
• Positive test for TB infection: either Tuberculin test (\>5mm, or \>10mm, based on epidemiologic and clinical factors and interpreted following local guidelines) or interferon gamma release assay based on Manufacturer's criteria; and,
• Recommended for Tuberculosis Preventive Treatment (TPT), following Canadian guidelines (for Canadian sites), and World Health Organization (WHO) guidelines (for international sites).