Short-Course Anti-tuberculosis Regimens for Mild Spinal Tuberculosis

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Mild Spinal Tuberculosis
• Intervention / Treatment: Drug: Rifampin; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Ethambutol; Drug: Rifapentine (RPT); Drug: Moxifloxacin

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wei Zhao, Ph.D; Phone Number: 86053188383308; Email: zhao4wei2@hotmail.com

Study Locations

• China
  • Jinan, China
    • Shandong Public Health Clinical Center
    • Contact: Qiang Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Empirical long course regimen; 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.	Drug: Rifampin; Rifampin: once daily, 600 mg.; Drug: Isoniazid; Isoniazid: once daily, 300 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.
Experimental: Short-course regimen; 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.	Drug: Isoniazid; Isoniazid: once daily, 300 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: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TB-recurrence rate of spinal tuberculosis at 24 months after completion of treatment.	The recurrence of spinal tuberculosis is defined by the reappearance of pain, with or without sinus formation, loosening or displacement of internal fixation on X-ray, and confirmed by postoperative CT or MRI showing increased local abscess, bone graft absorption, new sequestrum formation, or aggravated bone destruction.	24 months after completion of treatment
The proportion of participants with grade 3 or more adverse events during study medication		Throughout the study drug treatment period, about 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical cure at the end of therapy	Clinical Healing: Spinal symptoms improved; pre-disease function restored; weight gain; no instability/neuro deficits. Radiological Healing: Reduced epidural/paraspinal abscess/granulation; marrow reconversion; fatty bone reconstitution.	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		12 months after completion of treatment
The proportion of participants who are culture negative at eight weeks		At the end of 8 weeks of treatment
The proportion of discontinuation of assigned treatment for a reason other than microbiological ineligibility		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		Throughout the study drug treatment period, about 36 months
The proportion of participants who have residual neurological dysfunction		Throughout the study drug treatment period, about 36 months
PK parameters of the anti-TB drugs	Maximum Plasma Concentration [Cmax], etc	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	Cmax/MIC, etc	At the end of therapy, WEEK 52 for empirical long-course regimen, WEEK 26 for Short-course regimen

Collaborators and Investigators

• Sponsor: Shandong University
• Collaborators: Shandong Public Health Clinical Center
• Investigators: Principal Investigator: Wei Zhao, Ph.D, Shandong University

Study record dates

Study Major Dates

• Study Start (Estimated): April 5, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: March 25, 2025
• First Submitted That Met QC Criteria: March 31, 2025
• First Posted (Estimated): April 8, 2025

Study Record Updates

• Last Update Posted (Estimated): April 8, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Tuberculosis, Extrapulmonary; Bone Diseases; Musculoskeletal Diseases; Infections; Bone Diseases, Infectious; Spinal Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Spondylitis; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis, Osteoarticular; Tuberculosis; Tuberculosis, Spinal; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Nucleic Acid Synthesis Inhibitors; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Antibiotics, Antitubercular; Antitubercular Agents; Leprostatic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inducers; Fatty Acid Synthesis Inhibitors; Moxifloxacin; Rifampin; Ethambutol; Isoniazid; Pyrazinamide; Rifapentine
• Other Study ID Numbers: SDU-2024-RPT-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No