Subclinical TB With Innovative Modified Short-course Regimens

NCT ID: NCT06153069

Last Updated: 2023-12-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 556 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-01
• Study Completion Date: 2027-11-30

Brief Summary

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

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.

Conditions

Tuberculosis

Keywords

subclinical tuberculosis; shorter treatment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Short-Course Regimen

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.

Group Type: EXPERIMENTAL

Short-course regimen

Intervention Type: DRUG

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.

Standardized Regimen

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.

Group Type: ACTIVE_COMPARATOR

Standard regimen

Intervention Type: DRUG

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.

Interventions

Short-course regimen

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.

Intervention Type: DRUG

Standard regimen

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Huashan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Wen-hong Zhang

Director of Division of Infectious Diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wenhong Zhang, Dr.

Role: PRINCIPAL_INVESTIGATOR

Huashan Hospital of Fudan University，Shanghai，China

Locations

Huashan Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Hangzhou Red Cross Hospital

Hangzhou, Zhejiang, China

Countries

China

Other Identifiers

KY2023-715

Identifier Type: -

Identifier Source: org_study_id