Shortened Regimens for Drug-susceptible Pulmonary Tuberculosis

March 16, 2017 updated by: Tang Shenjie, Beijing Chest Hospital

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

3900

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China, 230000
        • Recruiting
        • Anhui Chest Hospital
        • Contact:
    • Beijing
      • Beijing, Beijing, China, 100000
        • Recruiting
        • Beijing Research Institute for Tuberculosis Control
        • Contact:
      • Beijing, Beijing, China, 101149
        • Recruiting
        • Beijing Chest Hospital,Capital Meical University
        • Contact:
    • Chongqing
      • Chongqing, Chongqing, China, 500106
        • Recruiting
        • Chongqing Infectious Disease Medical Center
        • Contact:
    • Gansu
      • Lanzhou, Gansu, China, 730000
        • Recruiting
        • Pulmonary Hospital of Lanzhou
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China, 510000
        • Recruiting
        • Centre for Tuberculosis Control of Guangdong Province
        • Contact:
    • Guangxi
      • Nanning, Guangxi, China, 530000
        • Recruiting
        • Guangxi Center for Disease Prevention and Control
        • Contact:
    • Hebei
      • Shijiazhuang, Hebei, China, 050000
        • Recruiting
        • HeBei Province Center for Disease Prevention and Control
        • Contact:
    • Heilongjiang
      • Ha'erbin, Heilongjiang, China, 150000
        • Recruiting
        • Infectious Disease Prevention Hospital in Heilongjiang Province
        • Contact:
      • Haerbin, Heilongjiang, China, 150000
        • Recruiting
        • Heilongjiang Province center for tuberculosis Control and Prevention
        • Contact:
      • Harbin, Heilongjiang, China, 150000
        • Recruiting
        • Harbin Chest Hospital
        • Contact:
    • Henan
      • Hebi, Henan, China, 458000
        • Recruiting
        • The Infectious Hospital of Hebi
        • Contact:
      • Kaifeng, Henan, China, 475000
        • Recruiting
        • Kaifeng Pulmonary Disease Hospital
        • Contact:
      • Nanyang, Henan, China, 473000
        • Recruiting
        • Sixth People's Hospital of Nanyang City
        • Contact:
      • Xianxiang, Henan, China, 453100
        • Recruiting
        • The First Affiliated Hospital of Xinxiang Medical University
        • Contact:
    • Hubei
      • Wuhan, Hubei, China, 430000
        • Recruiting
        • Wuhan Medical Treatment Center
        • Contact:
      • Wuhan, Hubei, China, 430030
        • Recruiting
        • Wuhan Institute For Tuberculosis Control
        • Contact:
    • Hunan
      • Changsha, Hunan, China, 410000
        • Recruiting
        • Hunan Institute For Tuberculosis Control
        • Contact:
    • Jiangsu
      • Nantong, Jiangsu, China, 226000
        • Recruiting
        • The Sixth People's Hospital of Nantong
        • Contact:
      • Suzhou, Jiangsu, China, 215000
        • Recruiting
        • The Fifth People's Hospital of Suzhou
        • Contact:
      • Zhenjiang, Jiangsu, China, 212005
        • Recruiting
        • The Third People's Hospital of Zenjiang
        • Contact:
    • Jilin
      • Changchun, Jilin, China, 130000
      • Jilin, Jilin, China, 132000
        • Recruiting
        • Tuberculosis Hospital in Jilin Province
        • Contact:
      • Shenyang, Jilin, China, 110000
        • Recruiting
        • China Shenyang Chest Hospital
        • Contact:
    • Ningxia
      • Yinchuan, Ningxia, China, 750000
        • Recruiting
        • The Fourth People's Hospital of Ningxia Autonomous Region
        • Contact:
    • Qinghai
      • Xining Shi, Qinghai, China, 810000
        • Recruiting
        • The 4th People's Hospital of Qinghai Province
        • Contact:
    • Shandong
      • Tengzhou, Shandong, China, 277500
        • Recruiting
        • The Infectious Disease Hospital of Wangkai Zaozhuang
        • Contact:
    • Shanghai
      • Shanghai, Shanghai, China, 200000
        • Recruiting
        • Shanghai pulmonary hospital
        • Contact:
    • Shanxi
      • Taiyuan, Shanxi, China, 030000
        • Recruiting
        • Taiyuan Fourth People's Hospital
        • Contact:
      • Xi'an, Shanxi, China, 710100
        • Recruiting
        • The Tuberculosis Prevention and Treatment Hospital of Shanxi Province
        • Contact:
    • Sichuan
      • Chengdu, Sichuan, China, 610061
        • Recruiting
        • Public health clinical center of chengdu
        • Contact:
    • Tianjin
      • Tianjin, Tianjin, China, 300000
        • Recruiting
        • Tianjin Haihe Hospital
        • Contact:
      • Tianjin, Tianjin, China, 300041
        • Recruiting
        • Tianjin centers for Disease Control and Prevention
        • Contact:
    • Xinjiang
      • Wulumuqi, Xinjiang, China, 830001
        • Recruiting
        • Chest of Hospital of Xinjiang Uygur Autonomous Region of the PRC
        • Contact:
    • Yunnan
      • Kunming, Yunnan, China, 650041
        • Recruiting
        • The Third People's Hospital of Kunming City
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: experimental group1

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).
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.
Drug: Rifampicin
Rifampicin is a widely used anti-tuberculosis medication.
Drug: Pyrazinamide
Pyrazinamide is a commonly used medication for tuberculosis, with bactericidal effect against intracellular mycobacterium tuberculosis.
Drug: Ethambutol
Ethambutol is a widely used medicine in anti-TB regimens with bacteriostatic effect against M. tb.
Drug: 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.
Other Names:
  • Cravit
Experimental: experimental group2
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.
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.
Drug: Rifampicin
Rifampicin is a widely used anti-tuberculosis medication.
Drug: Pyrazinamide
Pyrazinamide is a commonly used medication for tuberculosis, with bactericidal effect against intracellular mycobacterium tuberculosis.
Drug: Ethambutol
Ethambutol is a widely used medicine in anti-TB regimens with bacteriostatic effect against M. tb.
Active Comparator: Control regimen group

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).

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The percentage of participants with TB recurrence/relapse by 24 months after the end of treatment.
Time Frame: 24 months after treatment completion for all 3 groups
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.
Time Frame: 4.5 months after randomization for experimental group1 and 2; 6 months after randomization for control group
4.5 months after randomization for experimental group1 and 2; 6 months after randomization for control group

Secondary Outcome Measures

Outcome Measure
Time Frame
Treatment adverse reactions occuring
Time Frame: 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.
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 .
Time Frame: An avergae of 2-3 months after randomization.
An avergae of 2-3 months after randomization.
Sputum smear or culture conversion proportion at the treatment completion.
Time Frame: An average of 6 months for control group while 4.5 months for experimental group 1 and 2.
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.
Time Frame: An average of 6 months during treatment and 24 months after treatment completion.
An average of 6 months during treatment and 24 months after treatment completion.
Patiens adherence rate
Time Frame: An average of 6 months during treatment and 24 months after treatment completion.
An average of 6 months during treatment and 24 months after treatment completion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Chest Hospital

Collaborators

Wuhan Union Hospital, China
Shanghai Pulmonary Hospital, Shanghai, China
First Affiliated Hospital of Xinjiang Medical University
Anhui Chest Hospital
Hubei Provincial Center for Disease Control and Prevention
Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control
Kaifeng Central Hospital
Shenyang Chest Hospital
Tianjin Haihe Hospital
Centre for Tuberculosis Control of Guangdong Province
Hunan Institute For Tuberculosis Control
Wuhan Institute for Tuberculosis Control
Changchun Infectious Disease Hospital
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
The Infectious Disease Hospital of Wangkai Zaozhuang
The Third People's Hospital of Kunming City
The Infectious Hospital of Hebi
Pulmonary Hospital of Lanzhou
The Fourth People's Hospital of Ningxia Autonomous Region
The 4th 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

Investigators

  • Principal Investigator: Shenjie Tang, MD, Beijing Chest Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2016

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

December 1, 2018

Study Registration Dates

First Submitted

September 2, 2016

First Submitted That Met QC Criteria

September 11, 2016

First Posted (Estimate)

September 15, 2016

Study Record Updates

Last Update Posted (Actual)

March 20, 2017

Last Update Submitted That Met QC Criteria

March 16, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015ZX10003001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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