Shorter and Safer Treatment Regimens for Latent TB

Launched by MCGILL UNIVERSITY HEALTH CENTRE/RESEARCH INSTITUTE OF THE MCGILL UNIVERSITY HEALTH CENTRE · Jul 5, 2024

Keywords

ClinConnect Summary

This clinical trial is studying different ways to prevent tuberculosis (TB) infection in healthy people. Researchers want to find the safest and shortest treatment options that are still effective. They will compare a standard treatment of taking Rifampin for 4 months to some shorter regimens, including taking a higher dose of Rifampin for 2 months, and a combination of Levofloxacin and Rifapentine for just 1 month. The goal is to identify a treatment that is safe, easy to complete, and well-tolerated by both adults and children.

To participate in the trial, individuals must be at least 5 years old and have tested positive for TB infection. However, people currently suffering from TB disease, pregnant women, and those with certain medical conditions or allergies will not be eligible. Participants in the trial will take the assigned medication daily and will be closely monitored for safety and how well they tolerate the treatment. This trial is important because it could lead to shorter and easier preventive treatments for TB, making it more likely that people will complete their therapy.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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).
• Exclusion Criteria:
• • 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
• • Children aged 0-4 years;
• • 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;
• • Documented prior treatment for tuberculosis (TB) infection or disease;
• • Pre-enrolment - alanine transaminase (ALT), White Blood Cells, platelets or hemoglobin that correspond to a Grade 3 adverse event (AE);
• • Rifampin or rifapentine contra-indicated - due to allergy/hypersensitivity to any rifamycin (rifampin, rifabutin or rifapentine), or, drug interactions too difficult to manage;
• • 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);
• • 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.