Short-Course Anti-tuberculosis Regimens for Mild Spinal Tuberculosis

Shandong University

Status and phase: Not yet enrolling; Phase 2

Conditions: Mild Spinal Tuberculosis

Treatments: Drug: Ethambutol; Drug: Rifapentine (RPT); Drug: Isoniazid; Drug: Rifampin; Drug: Pyrazinamide; Drug: Moxifloxacin

Study type: Interventional

Funder types: Other

Identifiers

NCT06917495

SDU-2024-RPT-003

Details and patient eligibility

About

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.

Enrollment: 300 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 12 years.
2. 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.
3. Laboratory test values are completed within 14 days prior to screening.
4. 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.
5. For women of childbearing potential, a negative pregnancy test at or within seven (7) days prior to screening.
6. Karnofsky score greater than or equal to 60.
7. 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.
8. Written informed consent.

Exclusion criteria

• Exclusions Before Randomization:

1. Pregnant or breast-feeding.

2. Unable to take oral medications.

3. Previously enrolled in similar studies.

4. With spinal tumors or metastatic tumors.

5. Patients with mental disorders and cognitive dysfunction.

6. Received any investigational drug in the past 3 months.

7. More than five (5) days of treatment directed against active tuberculosis within 6 months preceding initiation of study drugs.

8. 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.

9. Known history of prolonged QT syndrome.

10. Weight less than 40.0 kg.

11. Known allergy or intolerance to any of the study medications.

12. 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.

13. Other medical conditions, that, in the investigator's judgment, make study participation not in the individual's best interest.

    • Exclusions After Randomization:

14. No M. tuberculosis is identified in the screening, baseline, and week 2 samples.

15. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 2 patient groups

Empirical long course regimen

Active Comparator group

Description:

Drug: Rifampicin, once daily, 600 mg, administered for 52 weeks. Drug: Isoniazid, once daily, 300 mg, administered for 52 weeks. Drug: Pyrazinamide, once daily, dosage adjusted based on body weight: 1000 mg for \< 55 kg, 1500 mg for ≥ 55-75 kg, and 2000 mg for \> 75 kg, administered for the first 8 weeks. Drug: Ethambutol, once daily, dosage adjusted based on body weight: 800 mg for \< 55 kg, 1200 mg for ≥ 55-75 kg, and 1600 mg for \> 75 kg, administered for the first 8 weeks.

Treatment:

Drug: Pyrazinamide

Drug: Rifampin

Drug: Isoniazid

Drug: Ethambutol

Short-course regimen

Experimental group

Description:

Drug: Rifapentine, once daily, 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, administered for 26 weeks. Drug: Moxifloxacin, once daily, 400 mg, administered for 26 weeks. Drug: Isoniazid, once daily, 300 mg, administered for 26 weeks. Drug: Pyrazinamide, once daily, dosage adjusted based on body weight: 1000 mg for \< 55 kg, 1500 mg for ≥ 55-75 kg, and 2000 mg for \>75 kg, administered for the first 8 weeks.

Treatment:

Drug: Pyrazinamide

Drug: Moxifloxacin

Drug: Rifapentine (RPT)

Drug: Isoniazid