Recruiting

Phase 2

Phase 3

TPT RegimensShorter and Safer Treatment Regimens for Latent TB

Sponsor:

McGill University Health Centre/Research Institute of the McGill University Health Centre

Code:

NCT06498414

Conditions

Tuberculosis Infection, Latent

Eligibility Criteria

Sex: All

Age: 5+

Healthy Volunteers: Not accepted

Interventions

rifampin standard arm

rifampin double dose

levofloxacin and rifapentine

Study Details

Brief summary:

Our study rationale is based on:

1. Tuberculosis Preventive Treatment (TPT) is given to healthy people and needs to be safe;
2. Tuberculosis Preventive Treatment (TPT) with shorter regimens are superior with respect to acceptance, completion, and costs;
3. 4 months of Rifampin 10mg/kg (4R10) is the safest regimen, but is completed by <80% of patients;
4. The safety of 2 months of Rifampin 20mg/kg (2R20) is similar to that of 4 months of Rifampin 10mg/kg (4R10), but completion is a concern;
5. 1-month regimens have promising efficacy;
6. Safety and tolerability must be carefully assessed with comparisons to 4 months of Rifampin 10mg/kg (4R10), and head-to-head with each other.

OBJECTIVES: The investigator will use a Bayesian adaptive Phase 2 randomized open-label trial design to test at least three experimental Tuberculosis Preventive Treatment (TPT) regimens to identify at least one regimen of ≤2 months duration that has non-inferior safety, completion, and tolerability in adults and children relative to the reference Tuberculosis Preventive Treatment (TPT) regimen. The shortest, safest, and best tolerated regimen identified in this Phase 2 trial will be tested for effectiveness and efficacy in a Phase 3 trial.

Specific Tuberculosis Preventive Treatment (TPT) regimens (All are daily and self-administered) Reference: Rifampin at a dose of 10 mg/kg/day for 4 months (4R10); Experimental: 1) Rifampin at 20 mg/kg/day for 2 months (2R20); (2) one month Levofloxacin and Rifapentine (1LP). At a later stage a 3rd experimental regimen will be selected and added: one another novel 1-2-month regimen identified from pre-clinical and clinical studies. When selected, this will be explained fully including preliminary data on safety and efficacy in an amended protocol and consent - which will be submitted for ethics and regulatory approval at that time).

Conditions

Tuberculosis Infection, Latent

Study ID

NCT06498414

Start date

Jun 10, 2025

Status verified date

Apr, 2026

Completion date

Jun 1, 2029

Anticipated

Primary completion date

Apr 1, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 5+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

1800 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: 4 months standard dose rifampin (4R10)

120 doses daily self-administered rifampin at 10 mg/kg/day (max. 600 mg/day)

experimental: 2 months high dose rifampin (2R20)

60 doses daily self-administered rifampin at 20 mg/kg/day (max.1200 mg/day)

experimental: 1 month levofloxacin and rifapentine (1LP)

30 doses daily self-administered levofloxacin (15 mg/kg/day, max. 750 mg/day and rifapentine (10mg/kg/day, max. 600mg)

Interventions

rifampin standard arm

120 doses daily self-administered rifampin at 10mg/kg/day (max 600mg/day)

rifampin double dose

60 doses daily self-administered rifampin at 20 mg/kg (max. 1200 mg/day)

levofloxacin and rifapentine

30 doses daily self-administered levofloxacin (15 mg/kg, max 750mg/day and rifapentine (10mg/kg, max: 600mg)

Primary outcome measure

Severe treatment-related Adverse Events (AE) [ Time Frame: From the start of the treatment until 2 weeks after the treatment completion ]

Central Contacts and Locations

Central contacts

Dick Menzies, MD

514-934-1934 dick.menzies@mcgill.ca

Chantal Valiquette

514-934-1934 chantal.valiquette@affiliate.mcgill.ca

Locations

Unviversity of Calgary

Recruiting

Calgary, Alberta, Canada

Contacts

Dina Fisher, MD

403-543-8339 dina.fisher@albertahealthservices.ca

Rachel Lim

403-944-7660 rachel.lim@albertahealthservices.ca

Principal Investigator:

Dina Fisher, MD

The Governors of the University of Alberta

Recruiting

Edmonton, Alberta, Canada, T6G 2C8

Contacts

Richard Long, MD

780-407-7223 richard.lung@ualberta.ca

Catherine Paulsen

780-289-5943 cpaulsen@ualberta.ca

Principal Investigator:

Richard Long, MD

BCCDC TB clinic

Recruiting

Vancouver, British Columbia, Canada

Contacts

James Johnston, Dr.

604-707-5662 james.johnston@bccdc.ca

Eri Flores

604-707-2400 eri.flores@bccdc.ca

Principal Investigator:

James Johnston, MD

University of Manitoba

Recruiting

Winnipeg, Manitoba, Canada

Contacts

Rachel Dwilow, MD

204-787-2071 rachel.dwilow@umanitoba.ca

Principal Investigator:

Rachel Dwilow, MD

University of Ottawa

Recruiting

Ottawa, Ontario, Canada

Contacts

Gonzalo Alvarez, MD

613-737-8899 galvarez@toh.ca

Principal Investigator:

Gonzalo Alvarez, MD

St. Michael's Hospital

Recruiting

Toronto, Ontario, Canada, M5B1W8

Contacts

Natasha Sabur, MD

natasha.sabur@unityhealth.to

Principal Investigator:

Natasha Sabur, MD

University Health Network

Recruiting

Toronto, Ontario, Canada, M6M2J5

Contacts

Sarah Brode, MD

416-603-5767 Sarah.Brode@uhn.ca

Principal Investigator:

Sarah Brode, MD

MUHC

Recruiting

Montreal, Quebec, Canada, H4A 3J1

Contacts

Dick Menzies, MD

514 934 1934 dick.menzies@mcgill.ca

Chantal Valiquette

514 934 1934 chantal.valiquette@affiliate.mcgil..ca

Principal Investigator:

Dick Menzies, MD

Hopital du Sacré-Coeur de Montreal

Recruiting

Montreal, Quebec, Canada, H4J 1C5

Contacts

Claire Trudel, MD

819-570-4752 claire.trudel@umontreal.ca

Principal Investigator:

Claire Trudel, MD

More Information

Sponsor

McGill University Health Centre/Research Institute of the McGill University Health Centre

Last update posted

May 11, 2026

Last verified

Apr, 2026

Keywords

Tuberculosis infection
Rifampin
Short treatment for latent tuberculosis
High dose rifampin

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by McGill University Health Centre/Research Institute of the McGill University Health Centre on 2026-05-11.