Asymptomatic TB With Innovative Modified Short-course Regimens

Official title

Clinical Efficacy of a Short-course Regimen for Asymptomatic Tuberculosis in China

Overview

This study is a randomized controlled trial among asymptomatic tuberculosis individuals aiming to assess whether the standard treatment duration can be shortened to 17 weeks without increasing the types or doses of anti-tuberculosis medications or 13 weeks with the high-dose rifapentine and moxifloxacin.

Detailed description

This study is a prospective, open-label, multicenter randomized controlled trial. The randomization process will use centralized stratified block randomization to minimize bias across province of participating sites.

Asymptomatic tuberculosis individuals included in the study will be randomly assigned in a 1:1:1 ratio to three groups: Standard Regimen Group, Four-month Regimen Group or Three-month Regimen Group. The standard 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 four-month regimen group follows the same regimen as the standard regimen group for the initial 8 weeks, followed by a continuation phase of daily rifampin (R) and isoniazid (H) for 9 weeks. The three-month regimen consists of high-dose rifapentine (P), isoniazid (H), pyrazinamide (Z), and moxifloxacin (M) for 8 weeks, followed high-dose Rifapentine (P), isoniazid (H), and moxifloxacin (M) for 5 weeks. For individuals in the four-month and the three-month regimen group, the treatment response will be evaluated at the end of the treatment phase. If the sputum culture remains positive at week 8, or if the radiological examination at the end of treatment still shows unclosed cavities, the continuation phase treatment will be extended by an additional 8 weeks.

Interventions

• Drug Four-month regimen
  The four-month regimen consists of a 17-week course of standard daily first-line anti-tuberculosis therapy, administered as either fixed-dose combinations or separate bulk drugs, in accordance with the recommendations of Technical Guidelines for Tuberculosis Prevention and Control in China. The treatment comprises an intensive phase of 8 weeks with Isoniazid (H) , Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E), followed by continuation phase of 9 weeks with HR. If the sputum culture remains
• Drug Three-month regimen
  Three-month regimen consists of two periods of 13-21 weeks. During the intensive phase (8 weeks), rifapentine 900 mg daily; moxifloxacin 400 mg daily; isoniazid 300 mg daily; pyrazinamide \<50.0kg 1000mg daily, 50.0-70.9kg 1500 mg daily, ≥71kg 2000mg daily. During the continuation phase (5 or 13 weeks based on the culture resultes and radiological manifestations), rifapentine 900 mg daily; moxifloxacin 400 mg daily; isoniazid 300 mg daily; All treatment is taken orally. For rifapentine administr
• Drug Standard regimen
  The standardized regimen consists of a 26-week course of standard daily first-line anti-tuberculosis therapy, administered as either fixed-dose combinations or separate bulk drugs, in accordance with the recommendations of Technical Guidelines for Tuberculosis Prevention and Control in China. The treatment comprises an intensive phase of 8 weeks with Isoniazid (H) , Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E), followed by continuation phase of 18 weeks with HR.

Primary outcome measures

• Favorable outcome rate in mITT pupulation [Time frame: At 78 weeks post-randomization]

Secondary outcome measures (9)

• Favorable outcome rate in assessable and PP population [Time frame: At 78 weeks post-randomization]
• Relapse rate post-treatment [Time frame: At 104 weeks post-randomization]
• The proportion of participants with sputum culture conversion [Time frame: At 8 weeks post-randomization]
• The proportion of grade 3 or greater adverse events [Time frame: From treatment initiation until two weeks after the last dose]
• Acquired drug resistance [Time frame: Post-treatment follow-up phase]
• Acceptability to regimens [Time frame: At the end of treatment]
• The overall index score of quality of life [Time frame: At the end of treatment and at 78 weeks post-randomization]
• Community transmission risk [Time frame: From treatment initiation]
• Serious adverse events [Time frame: From informed consent through final follow-up]

Eligibility criteria

Inclusion criteria

• 1\. Age between 14 to 80 years;
• 2\. Male or female;
• 3\. Willing to provide signed informed consent, or parental consent and participant assent;
• 4\. Individuals with respiratory tract specimen (including sputum/bronchoalveolar lavage fluid/lung tissue) positive for acid-fast bacilli smear/culture/molecular amplification for M. tuberculosis;
• 5\. No unexplained TB-suggestive symptoms in the three months prior to screening, including cough lasting more than two weeks, night sweats, fever or weight loss;
• 6\. If non-menopausal woman, agree to use or have used effective contraception during treatment.

Exclusion criteria

• 1\. Combined extrapulmonary tuberculosis;
• 2\. Induviduals with extensive lesion (lesion involvement exceeding 50% or the aggregate diameter of all cavities exceeding 6 cm) ;
• 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\. Individuals with impaired liver function (alanine transaminase \[ALT\] or total bilirubin \[TBIL\] more than 2.5 times the upper limit of normal) or combined with liver cirrhosis;
• 5\. Hemoglobin is less than 70g/L, or platelet is less than 50\*10\^9/L;
• 6\. Estimated Glomerular Filtration Rate (eGFR) is less than 30 mL/min/1.73m2;
• 7\. Known allergic or intolerant to any of the study drugs;
• 8\. Pregnant or breast-feeding;
• 9\. Prior anti-TB treatment for more than one week in the past six months;
• 10.Known history of epilepsy, uncontrolled diabetes;
• 11.For HIV-positive subjects, T-lymphocyte (CD4 cell) counts less than 100 cells/mm3;
• 12\. Unable to tolerant oral treatment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 5 centers

• Beijing Chest Hospital, Capital Medical University — Beijing
• Liupanshui City Third People's Hospital — Liupanshui
• Nayong County People's Hospital — Nayong
• Huashan Hospital of Fudan University — Shanghai
• The First People's Hospital of Linping District, Hangzhou — Hangzhou

Identifiers

NCT: NCT06153069 · KY2023-715

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗