Subclinical TB With Innovative Modified Short-course Regimens

Study Overview
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Brief Summary
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This study is a randomized controlled trial among subclinical tuberculosis patients aiming to assess whether the standard treatment duration can be shortened to 17 weeks or even 8 weeks without changing the current anti-tuberculosis drugs or dosages.

Detailed Description
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This study is a prospective, open-label, multicenter randomized controlled trial. The randomization process employs central stratified block randomization to balance biases across different centers, initially stratified according to each participating center. Considering that radiological findings are crucial factors influencing treatment outcomes, the study will group patients based on the presence or absence of lesions in pulmonary imaging. Subclinical tuberculosis patients included in the study will be randomly assigned in a 1:1 ratio to either the standard treatment group or the short-course treatment group. The standard treatment regimen consists of rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E) for 8 weeks, followed by rifampicin and isoniazid for an additional 18 weeks. The short-course treatment group follows the same regimen as the standard treatment group for the initial 8 weeks, and subsequent continuation treatment is determined based on the presence of radiological manifestations. Subclinical tuberculosis patients with radiological lesions will receive daily rifampicin and isoniazid for 9 weeks, resulting in a total treatment duration of 17 weeks. Those without radiological lesions will not undergo further continuation treatment, with a total treatment duration of 8 weeks.

Official Title
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Clinical Efficacy of a Short-course Regimen for Subclinical Tuberculosis in China

Conditions
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Tuberculosis

Intervention / Treatment
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* Drug: Short-course regimen
* Drug: Standard regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age between 14 to 80 years; 2. Male or female; 3. Weight between 40 to 80 kg; 4. Willing to provide signed informed consent, or parental consent and participant assent. 5. Individuals with respiratory tract specimen (including sputum/induced sputum/bronchoalveolar lavage fluid/lung tissue) smear/culture/rapid molecular tests-positive pulmonary tuberculosis; 6. No tuberculosis related symptoms that could not be explained by other causes within 6 months before enrollment. Tuberculosis related symptoms includes cough for more than 2 weeks, expectoration, hemoptysis, fever, night sweats, and weight loss. 7. Not received any anti-TB treatment in the past 6 months 8. If non-menopausal woman, agree to use or have used effective contraception during treatment. Exclusion Criteria: 1. Combined extrapulmonary tuberculosis; 2. Patients with extensive lesion (extent of disease greater than 50% or cavity size greater than 4cm) ; 3. 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; 4. Patients with impaired liver function (alanine transaminase [ALT], alkaline phosphatase [ALP] or total bilirubin [TBIL] more than 2 times the upper limit of normal) or combined with liver cirrhosis; 5. Leucocyte is less than 3×10^9/L, or hemoglobin is less than 90g/L, or platelet is less than 100*10^9/L; 6. Estimated Glomerular Filtration Rate (eGFR) is less than 60 mL/min/1.73m2 7. Known allergic or intolerant to any of the study drugs 8. Can not take oral medications 9. HIV antibody positive and AIDS patients 10.Have optic neuritis, alcoholism, epilepsy, mental illness, diabetes mellitus with fundus lesions, porphyria, myasthenia gravis 11.Pregnant or breast-feeding.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Short-Course Regimen<br>The short-course regimen consists of two periods of 8-17 weeks. During the first 8 weeks, the regimen consists of rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E). Then based on the presence of radiological manifestations, patients will be in divided into two sub-groups: with-radiological-lesions patients (with_R) and without-radiological-lesions patients (without_R). The regimen for with_R patients consists of rifampicin and isoniazid for an additional 9 weeks. Without_R patients will not undergo further continuation treatment, with a total treatment duration of 8 weeks. The regimen will be extended to 26 weeks if no culture conversion at the end of 8 weeks or the tuberculosis cavity is not closed at the end of treatment. | Drug: Short-course regimen<br>* During the intensive phase (8 weeks), rifampicin ≤50kg 450 mg daily, >50kg 600 mg daily; isoniazid 300 mg daily; pyrazinamide ≤50kg 1000mg daily, 50-70kg 1500mg daily, >70kg 2000mg daily; ethambutol ≤50kg 750mg daily, >50kg 1000mg daily; All treatment is taken orally. During the continuation phase (0 or 9 weeks based on the radiological manifestations), rifampicin ≤50kg 450 mg daily, >50kg 600 mg daily; isoniazid 300 mg daily; All treatment is taken orally.<br>|
| Active Comparator: Standardized Regimen<br>The standard treatment regimen consists of rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E) for 8 weeks, followed by rifampicin and isoniazid for an additional 18 weeks. | Drug: Standard regimen<br>* During the intensive phase (8 weeks), rifampicin ≤50kg 450 mg daily, >50kg 600 mg daily; isoniazid 300 mg daily; pyrazinamide ≤50kg 1000mg daily, 50-70kg 1500mg daily, >70kg 2000mg daily; ethambutol ≤50kg 750mg daily, >50kg 1000mg daily; All treatment is taken orally. During the continuation phase (18 weeks), rifampicin ≤50kg 450 mg daily, >50kg 600 mg daily; isoniazid 300 mg daily; All treatment is taken orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment success rate of the short-course regimen | To compare the treatment success rate without relapse between the short-course regimen group and the standardized regimen group. Treatment outcomes will be classified into favourable outcome and unfavourable outcome. | 78 weeks after treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment success rate of the short-course regimen | To compare the treatment success rate without relapse between the short-course regimen group and the standardized regimen group. Treatment outcomes will be classified into favourable outcome and unfavourable outcome. | 104 weeks after treatment initiation | 
| Relapse rate during follow-up | To compare the relapse rate between the short-course regimen group and the standardized regimen group. | 78 weeks after treatment initiation | 
| Culture conversion rate | Percentage of participants found to be culture-negative at the end of intensive phase and the end of treatment phase | 8 weeks after treatment initiation, the end of treatment | 
| Median time to Sputum Culture Conversion | Time from treatment initiation to the first of two consecutive negative sputum cultures without an intervening positive culture in liquid media | 8-26 weeks after treatment initiation | 
| The frequency of grade 3 or greater adverse events | To compare the proportion of patients who experience grade 3 or greater adverse events (graded according to the Division of AIDS severity criteria for adverse events), during treatment or follow-up, on the experimental regimen when compared to the control regimen | 8-26 weeks after treatment initiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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subclinical tuberculosis, shorter treatment