Clinical trial NCT06153069: Subclinical TB With Innovative Modified Short-course Regimens
Official title: Clinical Efficacy of a Short-course Regimen for Subclinical Tuberculosis in China
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Tuberculosis
Keywords: subclinical tuberculosis
shorter treatment
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2023-12-01
Enrollment: 556
Sex: ALL
Minimum age (years): 14
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Treatment success rate of the short-course regimen
timeFrame: 78 weeks after treatment initiation
Secondary outcomes:
measure: Treatment success rate of the short-course regimen
timeFrame: 104 weeks after treatment initiation
measure: Relapse rate during follow-up
timeFrame: 78 weeks after treatment initiation
measure: Culture conversion rate
timeFrame: 8 weeks after treatment initiation, the end of treatment
measure: Median time to Sputum Culture Conversion
timeFrame: 8-26 weeks after treatment initiation
measure: The frequency of grade 3 or greater adverse events
timeFrame: 8-26 weeks after treatment initiation
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital of Fudan University
state: Shanghai
city: Hangzhou
country: China
facility: Hangzhou Red Cross Hospital
state: Zhejiang
Study officials:
affiliation: Huashan Hospital of Fudan University，Shanghai，China
name: Wenhong Zhang, Dr.
role: PRINCIPAL_INVESTIGATOR
References: