Shortened Regimens for Drug-susceptible Pulmonary Tuberculosis
- Conditions
- Tuberculosis, Pulmonary
- Interventions
- Registration Number
- NCT02901288
- Lead Sponsor
- Beijing Chest Hospital
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 3900
- 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).
- Is aged 18-65 years.
- 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.
- Newly diagnosed cases receiving anti-TB treatment for less than one month
- Urine Human Chorionic Gonadotropin(U-HCG) negative and must agree to use effective contraception during the trial period.
- 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.
- Concomitant severe cardiovascular, liver, kidney, nervous system, hematopoietic system and other diseases, or concomitant neoplastic diseases. Or extensive lesion with respiratory insufficiency.
- Uncontrolled diabetes mellitus.
- Concomitant mental disorders.
- Is HIV positive.
- Is critically ill, and in the judgment of the investigator, not fit for the study or unlikely to complete the full course of study.
- Is known to be pregnant or breast-feeding.
- Is unable or unwilling to comply with the treatment, assessment, or follow-up schedule.
- Is taking any medications contraindicated with the medicines in any trial regimen of the study.
- Has a known allergy to any drug of treatment regimens.
- Is currently taking part in another trial.
- Has a QTc interval more than 480ms.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description experimental group2 Pyrazinamide The experimental group2 all oral regimen consisted of isoniazid,rifampin, pyrazinamide, and ethambutol for 4.5 months. The dosage of isoniazid,rifampin, pyrazinamide, and ethambutol is as same as that of control regimen. experimental group1 Isoniazid The experimental group1 all oral regimen is consisted of isoniazid,rifampin, pyrazinamide, ethambutol and levofloxacin for 4.5 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). experimental group1 Rifampicin The experimental group1 all oral regimen is consisted of isoniazid,rifampin, pyrazinamide, ethambutol and levofloxacin for 4.5 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). experimental group1 Pyrazinamide The experimental group1 all oral regimen is consisted of isoniazid,rifampin, pyrazinamide, ethambutol and levofloxacin for 4.5 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). experimental group1 Levofloxacin The experimental group1 all oral regimen is consisted of isoniazid,rifampin, pyrazinamide, ethambutol and levofloxacin for 4.5 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). experimental group1 Ethambutol The experimental group1 all oral regimen is consisted of isoniazid,rifampin, pyrazinamide, ethambutol and levofloxacin for 4.5 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). experimental group2 Rifampicin The experimental group2 all oral regimen consisted of isoniazid,rifampin, pyrazinamide, and ethambutol for 4.5 months. The dosage of isoniazid,rifampin, pyrazinamide, and ethambutol is as same as that of control regimen. experimental group2 Isoniazid The experimental group2 all oral regimen consisted of isoniazid,rifampin, pyrazinamide, and ethambutol for 4.5 months. The dosage of isoniazid,rifampin, pyrazinamide, and ethambutol is as same as that of control regimen. experimental group2 Ethambutol The experimental group2 all oral regimen consisted of isoniazid,rifampin, pyrazinamide, and ethambutol for 4.5 months. The dosage of isoniazid,rifampin, pyrazinamide, and ethambutol is as same as that of control regimen. Control regimen group Isoniazid The control all oral regimen consisted of isoniazid,rifampin, pyrazinamide, and ethambutol during the intensive phase of treatment (2 months), followed by isoniazid and rifampin during the continuation phase (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). . Control regimen group Rifampicin The control all oral regimen consisted of isoniazid,rifampin, pyrazinamide, and ethambutol during the intensive phase of treatment (2 months), followed by isoniazid and rifampin during the continuation phase (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). . Control regimen group Pyrazinamide The control all oral regimen consisted of isoniazid,rifampin, pyrazinamide, and ethambutol during the intensive phase of treatment (2 months), followed by isoniazid and rifampin during the continuation phase (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). . Control regimen group Ethambutol The control all oral regimen consisted of isoniazid,rifampin, pyrazinamide, and ethambutol during the intensive phase of treatment (2 months), followed by isoniazid and rifampin during the continuation phase (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). .
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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. Time to sputum smear or culture conversion within intensive phase . An avergae of 2-3 months after randomization. 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. Radiological manifestation change of TB lesion or cavity. An average of 6 months during treatment and 24 months after treatment completion. Patiens adherence rate An average of 6 months during treatment and 24 months after treatment completion.
Trial Locations
- Locations (35)
The Infectious Hospital of Hebi
🇨🇳Hebi, Henan, China
Wuhan Institute For Tuberculosis Control
🇨🇳Wuhan, Hubei, China
Anhui Chest Hospital
🇨🇳Hefei, Anhui, China
Chongqing Infectious Disease Medical Center
🇨🇳Chongqing, Chongqing, China
Pulmonary Hospital of Lanzhou
🇨🇳Lanzhou, Gansu, China
Beijing Chest Hospital,Capital Meical University
🇨🇳Beijing, Beijing, China
Beijing Research Institute for Tuberculosis Control
🇨🇳Beijing, Beijing, China
Guangxi Center for Disease Prevention and Control
🇨🇳Nanning, Guangxi, China
HeBei Province Center for Disease Prevention and Control
🇨🇳Shijiazhuang, Hebei, China
Centre for Tuberculosis Control of Guangdong Province
🇨🇳Guangzhou, Guangdong, China
Infectious Disease Prevention Hospital in Heilongjiang Province
🇨🇳Ha'erbin, Heilongjiang, China
Heilongjiang Province center for tuberculosis Control and Prevention
🇨🇳Haerbin, Heilongjiang, China
Harbin Chest Hospital
🇨🇳Harbin, Heilongjiang, China
Kaifeng Pulmonary Disease Hospital
🇨🇳Kaifeng, Henan, China
Sixth People's Hospital of Nanyang City
🇨🇳Nanyang, Henan, China
The First Affiliated Hospital of Xinxiang Medical University
🇨🇳Xianxiang, Henan, China
Wuhan medical treatment center
🇨🇳Wuhan, Hubei, China
Hunan Institute For Tuberculosis Control
🇨🇳Changsha, Hunan, China
The Sixth People's Hospital of Nantong
🇨🇳Nantong, Jiangsu, China
The Fifth People's Hospital of Suzhou
🇨🇳Suzhou, Jiangsu, China
The Third People's Hospital of Zenjiang
🇨🇳Zhenjiang, Jiangsu, China
Changchun Infectious Disease Hospital
🇨🇳Changchun, Jilin, China
Tuberculosis Hospital in Jilin Province
🇨🇳Jilin, Jilin, China
China Shenyang Chest Hospital
🇨🇳Shenyang, Jilin, China
The 4th People's Hospital of Qinghai Province
🇨🇳Xining Shi, Qinghai, China
The Fourth People's Hospital of Ningxia Autonomous Region
🇨🇳Yinchuan, Ningxia, China
The Infectious Disease Hospital of Wangkai Zaozhuang
🇨🇳Tengzhou, Shandong, China
Taiyuan Fourth People's Hospital
🇨🇳Taiyuan, Shanxi, China
The Tuberculosis Prevention and Treatment Hospital of Shanxi Province
🇨🇳Xi'an, Shanxi, China
Public Health Clinical Center of Chengdu
🇨🇳Chengdu, Sichuan, China
Tianjin Haihe Hospital
🇨🇳Tianjin, Tianjin, China
Tianjin centers for Disease Control and Prevention
🇨🇳Tianjin, Tianjin, China
Shanghai Pulmonary Hospital
🇨🇳Shanghai, Shanghai, China
Chest of Hospital of Xinjiang Uygur Autonomous Region of the PRC
🇨🇳Wulumuqi, Xinjiang, China
The Third People's Hospital of Kunming City
🇨🇳Kunming, Yunnan, China