Optimized treatment for drug-susceptible pulmonary tuberculosis

A Pragmatic Trial With Optimized Dose of Rifampicin and Moxifloxacin for the Treatment of Drug Susceptible Pulmonary Tuberculosis

This study is testing if a shorter 16-week treatment for drug-susceptible pulmonary tuberculosis, using a new combination of medications, is just as safe and effective as the standard 26-week treatment for adults, including those with HIV.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 414 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Kibong'oto Infectious Diseases Hospital (Government)
• Locations: 1 site (Moshi, Kilimanjaro)
• Trial ID: NCT05575518 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of two experimental regimens using optimized doses of rifampicin with or without moxifloxacin for treating drug-susceptible pulmonary tuberculosis. Participants will receive treatment for 16 weeks, compared to the standard 26-week regimen, with the aim of determining if the shorter treatment is as effective and safe. The study will involve individuals aged 18 and older with confirmed pulmonary TB, including those co-infected with HIV, across multiple sites in Gabon, Malawi, Mozambique, and Tanzania.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with bacteriologically confirmed drug-susceptible pulmonary tuberculosis.

Not a fit: Patients with drug-resistant tuberculosis or those who do not meet the inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to shorter and more effective treatment regimens for tuberculosis, improving patient outcomes and adherence.

How similar studies have performed: Other studies have shown promise in optimizing tuberculosis treatment regimens, but this specific approach is novel and aims to address current challenges in TB management.

Eligibility criteria

Inclusion Criteria:

* Each patient must meet all the following inclusion criteria prior to enrolment into the trial:

  1. The patient has given fully informed, signed written or witnessed oral informed consent for study participation prior to all trial-related procedures, including HIV testing if HIV status is not known.
  2. The patient has a diagnosis of pulmonary TB established by Xpert MTB/RIF® result which confirms "low" "medium" or "high" level detection of M tuberculosis and does not detect rifampicin resistance.

     1. If the patient has been referred from a clinic at which the pre-screening clinical diagnostic test for TB was an Xpert MTB/RIF® assay done at the trial laboratory, and the full read-out of that result is available, the test does not need to repeated to confirm eligibility.
     2. If the patient has been referred from a clinic at which the pre-screening clinical diagnostic test for TB was an Xpert MTB/RIF® assay done at a non-trial laboratory, but the full read-out of that result is available, the test does not need to repeated to confirm eligibility.
     3. If the patient has been referred to the study from a clinic from which the full pre-screening clinical diagnostic Xpert MTB/RIF® test result is unavailable, a repeat Xpert MTB/RIF® assay should be performed by the study laboratory to confirm eligibility before recruitment.
  3. The patient should be aged ≥ 18 years on the day of providing informed consent.
  4. The patient has a body weight in light clothing and without shoes of at least 35kg.
  5. Female patients of child-bearing potential must have a negative urine or serum pregnancy test ≤ 7 days prior to screening, and consent to practice an effective method of contraception until completion of therapy.
  6. The patient must have a verifiable residence location and telephone number that is accessible if necessary for contact during follow-up.

Exclusion Criteria:

* Patients for whom one of the following criteria is met will be excluded from the trial:

  1. There is concern about any circumstances that raise concern about free, informed consent to study participation.
  2. The patient's pre-screening or screening Xpert MTB/RIF® assay result is "negative","trace", or "very low" positive.
  3. At least one M tuberculosis isolate, either cultured or detected through molecular assays from sputum obtained from the patient prior to treatment initiation is found to be resistant to one or more of: rifampicin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones (late exclusion).
  4. The patient is in poor general condition where delay in treatment cannot be tolerated, or death within three months is likely, as assessed by the investigator.
  5. The patient had a nose/throat swab which was positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), on Polymerase Chain Reaction (PCR) or a rapid diagnostic test ≤ 14 days preceding study recruitment.
  6. The patient is pregnant or breast-feeding (female patients only).
  7. The patient is unable to take oral medications.
  8. The patient has received any investigational drug in the past three months.
  9. The patient has received more than five days of treatment directed against active tuberculosis ≤ 6 months preceding initiation of study drugs.
  10. The patient has known intolerance to any of the study drugs, or conditions for which they are contra-indicated.
  11. The patient is unwilling, or unable to adhere to requirements regarding restricted use of other medications during the study. Restricted medications will include medications which prolong the QTc interval, and CYP450 inhibitors or inducers.
  12. The patient is due to initiate, or requires continuation of, non-efavirenz, non-dolutegravir-based anti-retroviral therapy for HIV infection.
  13. The patient has decompensated liver disease and/or aminotransaminases \>3x upper limit of normal (ULN), serum total bilirubin level \>1.5x ULN or serum/plasma creatinine level \>x2 ULN.
  14. The patient has a baseline QTc interval of \>450ms.
  15. The patient is being, or about to be, treated for malaria.
  16. The patient has other medical conditions that, in the investigator's judgement, make study participation not in the individual's best interest.

Where this trial is running

Moshi, Kilimanjaro

• Kibong'oto Infectious Diseases Hospital — Moshi, Kilimanjaro, Tanzania (Recruiting)

Study contacts

• Study coordinator: Stellah Mpagama, PhD

Conditions Tuberculosis; Human Immunodeficiency Virus; TB/HIV; Phase III; Randomised