Tuberculosis, Pulmonary
Conditions
Keywords
pulmonary tuberculosis, shortened regimen, clinical trial
Brief summary
The purpose of the study is to evaluate the safety and efficacy of two shortened regimens for newly diagnosed smear positive drug susceptible pulmonary tuberculosis in comparison to World Health Organization recommended standard 6-month regimen.
Detailed description
1. Design: The study is a multi-center, randomized,controlled non-inferiority trial. 2. Population: patients with newly diagnosed drug-susceptible pulmonary TB who fulfill the inclusion and exclusion criteria. 3. Investigational regimens: Experimental group 1 regimen consists of levofloxacin, isoniazid , rifampicin,ethambutol and pyrazinamide for 4.5 months. Experimental group 2 regimen consists of isoniazid, rifampicin, ethambutol and pyrazinamide for 4.5 months. The control group is WHO recommended regimen conmposed of isoniazid , rifampicin, ethambutol and pyrazinamide for 2 months, followed by isoniazid , rifampicin for 4 months. Dosage: isoniazid 300mg(given once daily), rifampin 450mg(less than 50kg,given once daily)or 600mg(more than 50kg,given once daily), pyrazinamide 1500mg(less than 50kg,given once daily)or 30mg/kg(more than 50kg,once daily), ethambutol 750mg (less than 50kg,once daily) or 1000mg (more than 50kg,once daily), levofloxacin 600mg(less than 50kg,given once daily) or 800mg(more than 50kg,once daily).. 4. Trial objectives: to evaluate that shortened regimens is not inferior to standard treatment in terms of efficacy and safety for new smear positive pulmonary TB patients. 5. Primary and Secondary outcome measures: The primary efficacy outcome measures include (a)the percentage of participants with TB recurrence/relapse by 24 months after the end of treatment;(b) percentage of participants with treatment failure at either 4.5 months or 6 months after randomization. (a) Time to sputum smear or culture conversion within intensive phase.(b) Sputum smear conversion proportion at the treatment completion. (c) Number of adverse drug reaction occurring during treatment or follow-up period. (d) Radiological manifestation change of TB lesion or cavity.(e) Patients adherence rate. 6. Sample Size: Approximately 3900 participants will be enrolled and randomized with 1:1:1 ratio into either Experimental group1, Experimental group2 or control group. 7. Blinding: The study is an open-label study. 8. Assessment and follow-up: All patients will be followed by to 2 years after completion of treatment.
Interventions
DRUGIsoniazid
Isoniazid is a widely used anti-tuberculosis medication. Its primary action is to inhibit the synthesis of long-chain mycolic acids, which are unique components of mycobacterial cell wall.
DRUGRifampicin
Rifampicin is a widely used anti-tuberculosis medication.
DRUGPyrazinamide
Pyrazinamide is a commonly used medication for tuberculosis, with bactericidal effect against intracellular mycobacterium tuberculosis.
DRUGEthambutol
Ethambutol is a widely used medicine in anti-TB regimens with bacteriostatic effect against M. tb.
DRUGLevofloxacin
Levofloxacin is a commonly used antimicrobial for TB and other infections, which acts on the DNA-DNA-gyrase complex and topoisomerase IV. It is the S (-) enantiomer of the racemic active substance ofloxacin.
Sponsors
Hubei Provincial Center for Disease Control and Prevention
Centre for Tuberculosis Control of Guangdong Province
Hunan Institute For Tuberculosis Control
Anhui Chest Hospital
Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control
Wuhan Institute for Tuberculosis Control
Shanghai Pulmonary Hospital, Shanghai, China
Shenyang Chest Hospital
Changchun Infectious Disease Hospital
First Affiliated Hospital of Xinjiang Medical University
Public Health Clinical Center of Chengdu
Taiyuan Fourth People's Hospital
The Sixth People's Hospital of Nantong
The Tuberculosis Prevention and Treatment Hospital of Shanxi Province
Beijing Research Institute for Tuberculosis Control
Infectious Disease Prevention Hospital in Heilongjiang Province
The Third People's Hospital of Zhenjiang
Tianjin centers for Disease Control and Prevention
Harbin Chest Hospital
Chest of Hospital of Xinjiang Uygur Autonomous Region of the PRC
Heilongjiang Province center for tuberculosis Control and Prevention
Tianjin Haihe Hospital
The Infectious Disease Hospital of Wangkai Zaozhuang
The Third People's Hospital of Kunming City
Kaifeng Central Hospital
The Infectious Hospital of Hebi
Pulmonary Hospital of Lanzhou
The Fourth People's Hospital of Ningxia Autonomous Region
The Fourth People's Hospital of Qinghai Province
The Fifth People's Hospital of Suzhou
Chongqing Infectious Disease Medical Center
Tuberculosis Hospital in Jilin Province
Sixth People's Hospital of Nanyang City
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Beijing Chest Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Is willing and able to give informed consent to participate in the trial treatment and follow-up (signed or witnessed consent if the patient is illiterate). 2. Is aged 18-65 years. 3. Has twice positive acid-fast bacilli(AFB) sputum smear or positive sputum culture result, along with chest x-ray imaging consistent with active pulmonary tuberculosis. 4. Newly diagnosed cases receiving anti-TB treatment for less than one month 5. Urine Human Chorionic Gonadotropin(U-HCG) negative and must agree to use effective contraception during the trial period. 6. Has Alanine aminotransferase（ALT）and Total bilirubin（TBil） less than 2 times the upper limit of normal ; has Creatinine clearance rate （CrCI） more than 30ml/min; has Hemoglobin more than 7.0g/dL; has Platelet（PLT）more than 50 x10\^9/L before study entry.
Exclusion criteria
1. Concomitant severe cardiovascular, liver, kidney, nervous system, hematopoietic system and other diseases, or concomitant neoplastic diseases. Or extensive lesion with respiratory insufficiency. 2. Uncontrolled diabetes mellitus. 3. Concomitant mental disorders. 4. Is HIV positive. 5. Is critically ill, and in the judgment of the investigator, not fit for the study or unlikely to complete the full course of study. 6. Is known to be pregnant or breast-feeding. 7. Is unable or unwilling to comply with the treatment, assessment, or follow-up schedule. 8. Is taking any medications contraindicated with the medicines in any trial regimen of the study. 9. Has a known allergy to any drug of treatment regimens. 10. Is currently taking part in another trial. 11. Has a QTc interval more than 480ms.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The percentage of participants with TB recurrence/relapse by 24 months after the end of treatment. | 24 months after treatment completion for all 3 groups |
| Percentage of participants with treatment failure at either 4.5 months or 6 months after randomization. | 4.5 months after randomization for experimental group1 and 2; 6 months after randomization for control group |
Secondary
| Measure | Time frame |
|---|---|
| Sputum smear or culture conversion proportion at the treatment completion. | An average of 6 months for control group while 4.5 months for experimental group 1 and 2. |
| Treatment adverse reactions occuring | An average of 6 months for control group and 4.5 months for experimental group1 and 2 during treatment and 24 months after treatment completion. |
| Patiens adherence rate | An average of 6 months during treatment and 24 months after treatment completion. |
| Radiological manifestation change of TB lesion or cavity. | An average of 6 months during treatment and 24 months after treatment completion. |
| Time to sputum smear or culture conversion within intensive phase . | An avergae of 2-3 months after randomization. |
Countries
China
Contacts
Primary ContactShenjie Tang, MD
Outcome results
None listed