Shorter Regimens for Latent Tuberculosis

(SSTARLET Trial)

Not yet recruiting at 12 trial locations

Overseen By Dick Menzies, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

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

Must not be taking: QT-prolonging medications

Disqualifiers: Current TB, Pregnancy, Prior TB treatment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 1-4 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new, shorter treatments for preventing tuberculosis (TB) in individuals who have tested positive for TB infection but do not have active disease. The goal is to find a regimen as safe and easy to complete as the current standard of 4 months of Rifampin, but in 2 months or less. Participants will try different options, such as 2 months of high-dose Rifampin or a 1-month combination of Levofloxacin (an antibiotic) and Rifapentine (an antibiotic). This trial is suitable for individuals aged 5 and older who have a positive TB test and are recommended for preventative treatment. As a Phase 2/3 trial, the study measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking TB prevention strategies.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot participate if you are taking medications that prolong the QT interval and are not recommended with a fluoroquinolone.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that these tuberculosis treatments have been thoroughly studied for safety. For high-dose rifampin (20 mg/kg/day for 2 months), studies indicate it is as safe as the standard 4-month treatment (10 mg/kg/day). Most patients tolerate the higher dose well, similar to the standard dose, which is a positive sign for safety.

Research on levofloxacin and rifapentine (used together for one month) also suggests they are safe. Levofloxacin, at a dose of 15–20 mg/kg daily, has been shown to be safe in children, which is encouraging for adults too. Combining levofloxacin with rifapentine has not caused major safety issues in studies, meaning people generally handle the treatment well.

Overall, previous research suggests these treatments are expected to be safe. However, each person's experience may differ, and ongoing trials will help confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for latent tuberculosis because they offer potentially shorter and more convenient regimens compared to traditional options. The one-month combination of levofloxacin and rifapentine (1LP) is particularly noteworthy for its brevity, requiring only 30 doses, making it a faster option than the usual lengthy treatments. Additionally, the two-month high-dose rifampin regimen (2R20) delivers a potent dose that could enhance effectiveness while still cutting down treatment time compared to the typical six to nine-month courses. These innovations could significantly improve patient adherence and outcomes in managing latent TB.

What evidence suggests that this trial's treatments could be effective for latent tuberculosis?

This trial will compare different shorter regimens for preventing tuberculosis (TB). One treatment arm involves a combination of levofloxacin and rifapentine, which research indicates can lower the risk of developing TB by up to 70% in at-risk individuals. This combination shows promise for stopping TB. Another treatment arm involves high-dose rifampin, with evidence suggesting that a higher daily dose for two months might be as effective as the usual four-month treatment. While both treatments appear promising, their success depends on safety and patient adherence. ^{1 2 3 4 6}

Who Is on the Research Team?

Dick Menzies, MD

Principal Investigator

RI-MUHC

Are You a Good Fit for This Trial?

This trial is for individuals with latent TB or at risk of reactivating a TB infection. Participants should be healthy and able to take daily self-administered medication. The study excludes those who cannot follow the treatment plan, have conditions that might interfere with the drug's effectiveness, or are unable to provide informed consent.

Inclusion Criteria

I am at least 5 years old.

Positive test for TB infection: either Tuberculin test (>5mm, or >10mm, based on local guidelines) or interferon gamma release assay

I am recommended for TB preventive treatment as per Canadian or WHO guidelines.

Exclusion Criteria

I am allergic to or cannot take rifampin or rifapentine due to severe drug interactions.

My blood tests for liver function and blood cell counts are not showing severe problems.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of the Tuberculosis Preventive Treatment (TPT) regimens: 4 months of Rifampin 10mg/kg, 2 months of Rifampin 20mg/kg, or 1 month of Levofloxacin and Rifapentine

1-4 months

In-person visits at 2 weeks and end-of-treatment, with additional phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment, including detection of late adverse events and incident tuberculosis

26 months

Contact every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Levofloxacin and Rifapentine
• Rifampin

Trial Overview The trial is testing three different TB preventive treatments: a standard dose of rifampin for four months, a double dose of rifampin for two months, and one month of levofloxacin with rifapentine. It aims to find a regimen under two months long that's as safe and tolerable as the four-month reference treatment.

How Is the Trial Designed?

Group I: 2 months high dose rifampin (2R20) Experimental Treatment 1 Intervention

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

Group II: 1 month levofloxacin and rifapentine (1LP) Experimental Treatment 1 Intervention

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

Group III: 4 months standard dose rifampin (4R10) Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

476

Recruited

170,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

Higher doses of rifamycins are being tested in shorter treatment regimens for tuberculosis, which could potentially reduce the duration of therapy compared to the standard six-to-nine month course.

New drugs like moxifloxacin, gatifloxacin, and SQ109 show promise in shortening treatment times and enhancing the effectiveness of existing regimens, but it may take at least a decade for these new treatments to be fully developed and used in practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New drugs for tuberculosis treatment. Sánchez, F., López Colomés, JL., Villarino, E., et al.[2015]

Daily rifapentine-based regimens showed comparable efficacy to the standard rifampin+pyrazinamide regimen in treating latent tuberculosis infection (LTBI) in a mouse model, suggesting they could potentially shorten treatment duration to 6 to 8 weeks.

Existing regimens like isoniazid and rifampin were less effective, with many mice remaining culture-positive after 8 weeks, highlighting the improved effectiveness of rifapentine-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-course therapy with daily rifapentine in a murine model of latent tuberculosis infection. Zhang, T., Zhang, M., Rosenthal, IM., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12506051/

Comparative efficacy and safety of high-dose rifamycin ... High-dose rifamycin (HDR) regimens have demonstrated significant potential in tuberculosis (TB) treatment. This study aims to evaluate the ...

2. thelancet.com thelancet.com/journals/lanres/article/PIIS2213-2600(24)00076-6/abstract

High-dose, short-duration versus standard rifampicin for ... The two co-primary outcomes were safety (in the safety population, in which participants received at least one dose of the study drug) and ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2213260024000766

High-dose, short-duration versus standard rifampicin for ... In this trial, 2 months of 30 mg/kg daily rifampicin had significantly worse safety and completion than 4 months of 10 mg/kg daily and 2 months of 20 mg/kg ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03988933

2R2: Higher Dose Rifampin for 2 Months vs Standard ... Shorter regimens of high dose daily rifampin may be safe, and as effective as the standard rifampin regimen when taken for 4 months to treat latent TB (LTBI).

5. academic.oup.com academic.oup.com/cid/article/81/1/143/7950999

High Time for Higher-Dose Rifampin - Oxford Academic One can argue that the “maximally effective dose” of rifampin has not been established in the mouse. At doses of ≥810 mg/kg , efficacy was still increasing, ...

6. academic.oup.com academic.oup.com/ofid/article/11/3/ofae034/7596644

Safety and Efficacy of 25 mg/kg and 35 mg/kg vs 10 mg/kg ... Rifampicin is a potential treatment-shortening agent because dose escalation from 10 to 35 mg/kg/day is safe and leads to a rapid fall in both ...