Shorter, Safer Preventive Treatment for Latent TB

SSTARLET: Shorter and Safer Treatment Regimens for Latent TB

This trial will test whether shorter preventive treatments—higher‑dose rifampin for two months or one‑month rifapentine combinations—are as safe and easier to finish as the current four‑month rifampin regimen for people with latent tuberculosis.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 1800 (estimated)
• Ages: 5 Years and up
• Sex: All
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre (Academic / other)
• Locations: 14 sites (Cotonou and 13 other locations)
• Trial ID: NCT06498414 on ClinicalTrials.gov

What this trial studies

This is an open‑label, multi‑arm Bayesian adaptive Phase 2/3 trial comparing the reference regimen of 4 months rifampin 10 mg/kg (4R10) to at least two experimental shorter regimens (2 months rifampin 20 mg/kg [2R20] and one month levofloxacin plus rifapentine [1LP]) with a possible third one‑month regimen added later. Regimens that fail pre‑specified safety, completion, or tolerability criteria will be dropped and randomization will be adjusted to prioritize promising arms. Primary outcomes are safety, treatment completion, and tolerability in adults and children aged ≥5 years who are eligible for tuberculosis preventive treatment. The protocol includes informed consent updates and ethics review when a new experimental regimen is added.

Who should consider this trial

Good fit: Adults and children aged 5 years and older (weight >15 kg) with a positive test for TB infection who are recommended for preventive treatment under local or WHO guidelines are eligible.

Not a fit: People with active TB disease, known contraindications to rifamycins or the study drugs, or significant medical comorbidities (for example severe liver disease) are unlikely to benefit from these regimens.

Why it matters

Potential benefit: If successful, patients could receive much shorter preventive treatment that is equally safe and easier to complete, reducing the risk of progression to active TB.

How similar studies have performed: Previous trials support the safety of 4R10 and show promising efficacy and safety for one‑month rifapentine combinations and higher‑dose rifampin, but direct head‑to‑head data on safety, completion, and tolerability are limited.

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.

Where this trial is running

Cotonou and 13 other locations

• Centre National Hospitalier Universitaire de Pneumo Phtisiologie de Cotonou (CNHU-PPC) — Cotonou, Benin (Not_yet_recruiting)
• Manaus — Manaus, Brazil (Recruiting)
• Unviversity of Calgary — Calgary, Alberta, Canada (Recruiting)
• The Governors of the University of Alberta — Edmonton, Alberta, Canada (Recruiting)
• BCCDC TB clinic — Vancouver, British Columbia, Canada (Recruiting)
• University of Manitoba — Winnipeg, Manitoba, Canada (Recruiting)
• University of Ottawa — Ottawa, Ontario, Canada (Recruiting)
• St. Michael's Hospital — Toronto, Ontario, Canada (Recruiting)
• University Health Network — Toronto, Ontario, Canada (Recruiting)
• Muhc — Montreal, Quebec, Canada (Recruiting)
• Hopital du Sacré-Coeur de Montreal — Montreal, Quebec, Canada (Recruiting)
• Universitas Padjadjaran, Klinik Penelitian Tuberculosis (TB research clinic) — Bandung, Indonesia (Recruiting)
• Can Tho Lung Hospital — Can Tho, Vietnam (Recruiting)
• National Lung Hospital — Hanoi, Vietnam (Recruiting)

Study contacts

• Principal investigator: Dick Menzies, MD — Ri-Muhc
• Study coordinator: Dick Menzies, MD

Conditions Tuberculosis Infection, Latent; Tuberculosis infection; Rifampin; Short treatment for latent tuberculosis; High dose rifampin