Short-Course Anti-tuberculosis Regimens for Mild Spinal Tuberculosis

Official title

Rifapentine- And Moxifloxacin-Containing Short-Course Regimens for Mild Spinal Tuberculosis: A Multicenter, Randomized, Non-inferiority Clinical Trial

Overview

To evaluate the non-inferiority in efficacy between the rifapentine- and moxifloxacin-containing short-course regimens (with rifampicin replaced by rifapentine and ethambutol replaced by moxifloxacin, while isoniazid and pyrazinamide remaining the same as the empirical regimen) and the empirical long-course regimen, so as to determine whether it is possible to shorten the treatment duration to 26 weeks for patients with mild spinal tuberculosis.

Interventions

• Drug Rifampin
  Rifampin: once daily, 600 mg.
• Drug Isoniazid
  Isoniazid: once daily, 300 mg.
• Drug Rifapentine (RPT)
  Rifapentine: once daily with dosage adjusted based on body weight: 750 mg for ≤41.2 kg, 900 mg for \>41.3-48.7 kg, 1050 mg for \> 48.8-56.2 kg, 1200 mg for ≥ 56.3 kg.
• Drug Moxifloxacin
  Moxifloxacin: once daily, 400 mg.
• Drug Pyrazinamide
  Pyrazinamide: once daily with dosage adjusted based on body weight: 1000 mg for \< 55 kg, 1500 mg for ≥ 55-75 kg, and 2000 mg for \>75 kg.
• Drug Ethambutol
  Ethambutol: once daily with dosage adjusted based on body weight: 800 mg for \< 55 kg, 1200 mg for ≥ 55-75 kg, and 1600 mg for \> 75 kg.

Primary outcome measures

• TB-recurrence rate of spinal tuberculosis at 24 months after completion of treatment. [Time frame: 24 months after completion of treatment]
• The proportion of participants with grade 3 or more adverse events during study medication [Time frame: Throughout the study drug treatment period, about 36 months]

Secondary outcome measures (8)

• Clinical cure at the end of therapy [Time frame: At the end of therapy, WEEK 52 for empirical long-course regimen, WEEK 26 for Short-course regimen]
• TB-recurrence rate of spinal tuberculosis 12 months after completion of treatment [Time frame: 12 months after completion of treatment]
• The proportion of participants who are culture negative at eight weeks [Time frame: At the end of 8 weeks of treatment]
• The proportion of discontinuation of assigned treatment for a reason other than microbiological ineligibility [Time frame: Throughout the study period, an average of 1 year, up until the point of treatment discontinuation due to reasons other than microbiological failure]
• The incidence of adverse events [Time frame: Throughout the study drug treatment period, about 36 months]
• The proportion of participants who have residual neurological dysfunction [Time frame: Throughout the study drug treatment period, about 36 months]
• PK parameters of the anti-TB drugs [Time frame: At the end of therapy, WEEK 52 for empirical long-course regimen, WEEK 26 for Short-course regimen]
• PD target attainment rate of the anti-TB drugs [Time frame: At the end of therapy, WEEK 52 for empirical long-course regimen, WEEK 26 for Short-course regimen]

Eligibility criteria

Inclusion criteria

• Age ≥ 12 years.
• Based on the medical history, clinical manifestations, radiological, laboratory tests and possible histological samples, the diagnostic criteria are met and judged to be mild spinal tuberculosis.
• Laboratory test values are completed within 14 days prior to screening.
• Women of child-bearing potential who are not surgically sterilized must agree to practice a barrier method of contraception or abstain from heterosexual intercourse during study drug treatment.
• For women of childbearing potential, a negative pregnancy test at or within seven (7) days prior to screening.
• Karnofsky score greater than or equal to 60.
• A verifiable address or residence location that is readily accessible for visiting, and willingness to inform the study team of any change of address during the treatment and follow-up period.
• Written informed consent.

Exclusion criteria

\- Exclusions Before Randomization:

• Pregnant or breast-feeding.
• Unable to take oral medications.
• Previously enrolled in similar studies.
• With spinal tumors or metastatic tumors.
• Patients with mental disorders and cognitive dysfunction.
• Received any investigational drug in the past 3 months.
• More than five (5) days of treatment directed against active tuberculosis within 6 months preceding initiation of study drugs.
• More than five (5) days of systemic treatment with any one or more of the following drugs within 30 days preceding initiation of study drugs: Isoniazid, rifampin, rifambutin, rifabentine, ethambutol, pyrazinamide, kanamycin, amikacin, streptomycin, capreomycin, moxifloxacin, levofloxacin, gatifloxacin, ofloxacin, ciprofloxacin, other fluoroquinolones, ethionamide, prothionamide, cycloserine, terizidone, para-aminosalicylic acid, linezolid, clofazimine, delamanid or bedaquiline.
• Known history of prolonged QT syndrome.
• Weight less than 40.0 kg.
• Known allergy or intolerance to any of the study medications.
• Individuals will be excluded from enrollment if, at the time of enrollment, their M. tuberculosis isolate is already known to be resistant to any one or more of the following: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones.
• Other medical conditions, that, in the investigator's judgment, make study participation not in the individual's best interest.

• Exclusions After Randomization:
• No M. tuberculosis is identified in the screening, baseline, and week 2 samples.
• Mycobacterium tuberculosis grown from or tested by molecular assays (Xpert MTB / RIF) in samples obtained before or after the study are determined to be resistant to isoniazid, rifampicin, or fluoroquinolones.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shandong Public Health Clinical Center — Jinan

Publications

• Wu YE, Cao J, Wang L, Wei YJ, Liu HX, Qi L, Zhang W, Liu F, Zhu ZJ, Fan XT, Wang S, Chen C, Liu XZ, Li Y, Sun ZZ, Pan JB, Yang CQ, Van Den Anker J, Zhang Q, Zhao W. Rifapentine- and moxifloxacin-containing short-course regimens for mild spinal tuberculosis: study protocol for a multicenter, randomized, non-inferiority phase II clinical trial. Front Pharmacol. 2025 Dec 19;16:1684771. doi: 10.3389/f PMID 41487489

Identifiers

NCT: NCT06917495 · SDU-2024-RPT-003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗