Shortened Regimens for Drug-susceptible Pulmonary Tuberculosis

Tuberculosis, Pulmonary Clinical Trial

Official title:

Shortened Regimens for First Diagnosed Smear Positive Drug Susceptible Pulmonary Tuberculosis: a Randomised Controlled Non-inferiority Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02901288
• Other study ID #: 2015ZX10003001
• Status: Recruiting
• Phase: Phase 4
• First received: September 2, 2016
• Last updated: March 16, 2017
• Start date: August 2016
• Est. completion date: December 2018

Study information

• Verified date: March 2017
• Source: Beijing Chest Hospital
• Contact: Shenjie Tang, MD
• Email: tangsj1106[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 3900
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

Drug:
• Isoniazid
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.
• Rifampicin
Rifampicin is a widely used anti-tuberculosis medication.
• Pyrazinamide
Pyrazinamide is a commonly used medication for tuberculosis, with bactericidal effect against intracellular mycobacterium tuberculosis.
• Ethambutol
Ethambutol is a widely used medicine in anti-TB regimens with bacteriostatic effect against M. tb.
• Levofloxacin
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.

Locations

Country	Name	City	State
China	Beijing Chest Hospital,Capital Meical University	Beijing	Beijing
China	Beijing Research Institute for Tuberculosis Control	Beijing	Beijing
China	Changchun Infectious Disease Hospital	Changchun	Jilin
China	Hunan Institute For Tuberculosis Control	Changsha	Hunan
China	Public Health Clinical Center of Chengdu	Chengdu	Sichuan
China	Chongqing Infectious Disease Medical Center	Chongqing	Chongqing
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	The Infectious Hospital of Hebi	Hebi	Henan
China	Anhui Chest Hospital	Hefei	Anhui
China	Tuberculosis Hospital in Jilin Province	Jilin	Jilin
China	Kaifeng Pulmonary Disease Hospital	Kaifeng	Henan
China	The Third People's Hospital of Kunming City	Kunming	Yunnan
China	Pulmonary Hospital of Lanzhou	Lanzhou	Gansu
China	Guangxi Center for Disease Prevention and Control	Nanning	Guangxi
China	The Sixth People's Hospital of Nantong	Nantong	Jiangsu
China	Sixth People's Hospital of Nanyang City	Nanyang	Henan
China	Shanghai Pulmonary Hospital	Shanghai	Shanghai
China	China Shenyang Chest Hospital	Shenyang	Jilin
China	HeBei Province Center for Disease Prevention and Control	Shijiazhuang	Hebei
China	The Fifth People's Hospital of Suzhou	Suzhou	Jiangsu
China	Taiyuan Fourth People's Hospital	Taiyuan	Shanxi
China	The Infectious Disease Hospital of Wangkai Zaozhuang	Tengzhou	Shandong
China	Tianjin centers for Disease Control and Prevention	Tianjin	Tianjin
China	Tianjin Haihe Hospital	Tianjin	Tianjin
China	Wuhan Institute For Tuberculosis Control	Wuhan	Hubei
China	Wuhan medical treatment center	Wuhan	Hubei
China	Chest of Hospital of Xinjiang Uygur Autonomous Region of the PRC	Wulumuqi	Xinjiang
China	The Tuberculosis Prevention and Treatment Hospital of Shanxi Province	Xi'an	Shanxi
China	The First Affiliated Hospital of Xinxiang Medical University	Xianxiang	Henan
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 Third People's Hospital of Zenjiang	Zhenjiang	Jiangsu

Sponsors (35)

Lead Sponsor

Collaborator

Beijing Chest Hospital

Anhui Chest Hospital, Beijing Research Institute for Tuberculosis Control, Centre for Tuberculosis Control of Guangdong Province, Changchun Infectious Disease Hospital, Chest of Hospital of Xinjiang Uygur Autonomous Region of the PRC, China Shenyang Chest Hospital, Chongqing Infectious Disease Medical Center, First Affiliated Hospital of Xinjiang Medical University, Guangxi Center for Disease Prevention and Control, Harbin Chest Hospital, Heilongjiang Province center for tuberculosis Control and Prevention, Hubei Provincial Center for Disease Control and Prevention, Hunan Institute For Tuberculosis Control, Infectious Disease Prevention Hospital in Heilongjiang Province, Kaifeng Pulmonary Disease Hospital, Public Health Clinical Center of Chengdu, Pulmonary Hospital of Lanzhou, Shanghai Pulmonary Hospital, Shanghai, China, Sixth People's Hospital of Nanyang City, Taiyuan Fourth People's Hospital, The 4th People's Hospital of Qinghai Province, The Fifth People's Hospital of Suzhou, The Fourth People's Hospital of Ningxia Autonomous Region, The Infectious Disease Hospital of Wangkai Zaozhuang, The Infectious Hospital of Hebi, The Sixth People's Hospital of Nantong, The Third People's Hospital of Kunming City, The Third People's Hospital of Zhenjiang, The Tuberculosis Prevention and Treatment Hospital of Shanxi Province, Tianjin centers for Disease Control and Prevention, Tianjin Haihe Hospital, Tuberculosis Hospital in Jilin Province, Wuhan Institute for Tuberculosis Control, Wuhan medical treatment center

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.
Secondary	Time to sputum smear or culture conversion within intensive phase .		An avergae of 2-3 months after randomization.
Secondary	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.
Secondary	Radiological manifestation change of TB lesion or cavity.		An average of 6 months during treatment and 24 months after treatment completion.
Secondary	Patiens adherence rate		An average of 6 months during treatment and 24 months after treatment completion.