Comparing high and standard doses of rifampicin for tuberculosis treatment

Pragmatic Trial on the Safety and Tolerability of an Optimized Dose of Rifampicin in Tuberculosis Patients

This study is testing whether a higher dose of rifampicin can help people with pulmonary tuberculosis get better without causing more side effects compared to the standard lower doses.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 164 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Radboud University Medical Center (other)
• Locations: 2 sites (Turin and 1 other locations)
• Trial ID: NCT06057519 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness and safety of an optimized dose of rifampicin (1800 mg) compared to standard doses (450 mg or 600 mg based on weight) in patients with pulmonary tuberculosis. The study will assess the incidence of hepatotoxicity, adverse events, treatment outcomes, and culture conversion rates between the two dosing regimens. Participants will receive the optimized dose daily, and researchers will analyze the pharmacokinetics of both dosing strategies to determine the best approach for treatment.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older diagnosed with pulmonary tuberculosis who have no prior adverse reactions to rifampicin.

Not a fit: Patients with known allergies or toxicity to rifampicin, or those who are pregnant or lactating, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment outcomes and reduced side effects for patients with tuberculosis.

How similar studies have performed: Other studies have explored dosing regimens for tuberculosis treatment, but this specific optimized dosing approach is novel.

Eligibility criteria

Inclusion Criteria:

* The patient has provided informed consent for study participation prior to all trial-related procedures.
* The patient has a diagnosis of pulmonary tuberculosis according to the local diagnostic criteria.
* The patient is aged 18 years or older at the day of informed consent.
* No known allergic reactions or toxicity to rifampicin in the past.
* Female patients of childbearing potential must have a negative serum pregnancy test, and consent to practice an effective method of birth control during the study. And they should not be lactating during the trial (female participants of childbearing potential only). Effective birth control for female patients has to include two methods, including methods that the patient's sexual partner(s) use. At least one must be a barrier method. Female patients are considered not to be of childbearing potential if they are post-menopausal with no menses for the last 12 months, or surgically sterile (this condition is fulfilled by bilateral oophorectomy, hysterectomy, and by tubal ligation which is done at least 12 months prior to enrolment).
* The patient will be compliant to the study schedule, in the discretion of the investigator.

Exclusion Criteria:

* The patient has tuberculosis which is assessed to receive high dose rifampicin according to the local standard of care.
* The patient started current TB treatment more than 4 weeks ago.
* The patient has TB meningitis.
* The patient is in a coma.
* Circumstances that raise doubt about free, uncoerced consent to study participation (e.g. in a prisoner or mentally handicapped person)
* The patient is not able to give consent personally.
* Poor general condition or comorbidities where delay in treatment cannot be tolerated or death within three months is likely. Or if there is concurrent treatment that may interfere.
* The patient is pregnant or breast-feeding.
* Patient infected with a rifampicin-resistant strain of M. tuberculosis.
* Known allergy or intolerance for rifamycins.
* The participant has a known or suspected, current alcohol or drug or amphetamine abuse, that is, in the opinion of the investigator, sufficient to compromise the safety or cooperation of the patient.
* The patient has a known allergy or intolerance, or concomitant disorders or conditions for which rifamycins or other standard TB treatment drugs are contraindicated.
* The patient has had treatment with any other investigational drug within 1 month prior to enrolment, or enrolment into other clinical (intervention) trials is planned in the upcoming 6 months
* Laboratory: at screening one or more of the following abnormalities were observed for the patient in screening laboratory:

  * Serum amino aspartate transferase (AST) and/or serum alanine aminotransferase (ALT) activity \>3x the upper limit of normal
  * Serum total bilirubin level \>2.5 times the upper limit of normal
  * Creatinine clearance (CrCl) level lower than 30 mls/min
* Acute or severe or life-threatening liver disease induced by drugs in the past
* The patient has a chronic disorder such as liver disease or renal disease.
* The patient has icterus.
* Previous anti-TB treatment: the patient ended a previous TB treatment (episode) within last 3 months.

Where this trial is running

Turin and 1 other locations

• ASL Città di Torino — Turin, Italy (RECRUITING)
• Radboud University Medical Centre — Nijmegen, Netherlands (RECRUITING)

Study contacts

• Principal investigator: Martin Boeree — Radboud University Medical Center
• Study coordinator: Jodie Schilkdraut, PhD

Conditions: Tuberculosis, Pulmonary