Shortened Regimens for Drug-susceptible Pulmonary Tuberculosis

NCT02901288 | Unknown Phase 4

• 1 other identifier: 2015ZX10003001
• Study Type: interventional
• Target: 3,900
• Locations: 1 country
• Sites: 35

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.

Conditions

Tuberculosis, Pulmonary

Keywords

pulmonary tuberculosis; shortened regimen; clinical trial

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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.

Study Arms (3)

experimental group1

EXPERIMENTAL

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; Drug: Rifampicin; Drug: Pyrazinamide; Drug: Ethambutol; Drug: Levofloxacin

experimental group2

EXPERIMENTAL

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; Drug: Rifampicin; Drug: Pyrazinamide; Drug: Ethambutol

Control regimen group

ACTIVE COMPARATOR

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; Drug: Rifampicin; Drug: Pyrazinamide; Drug: Ethambutol

Interventions

Isoniazid DRUG

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.

Control regimen group; experimental group1; experimental group2

Rifampicin DRUG

Rifampicin is a widely used anti-tuberculosis medication.

Control regimen group; experimental group1; experimental group2

Pyrazinamide DRUG

Pyrazinamide is a commonly used medication for tuberculosis, with bactericidal effect against intracellular mycobacterium tuberculosis.

Control regimen group; experimental group1; experimental group2

Ethambutol DRUG

Ethambutol is a widely used medicine in anti-TB regimens with bacteriostatic effect against M. tb.

Control regimen group; experimental group1; experimental group2

Levofloxacin DRUG

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.

Also known as: Cravit

experimental group1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (35)

Anhui Chest Hospital

Hefei, Anhui, 230000, China

RECRUITING

Beijing Research Institute for Tuberculosis Control

Beijing, Beijing Municipality, 100000, China

RECRUITING

Beijing Chest Hospital,Capital Meical University

Beijing, Beijing Municipality, 101149, China

RECRUITING

Chongqing Infectious Disease Medical Center

Chongqing, Chongqing Municipality, 500106, China

RECRUITING

Pulmonary Hospital of Lanzhou

Lanzhou, Gansu, 730000, China

RECRUITING

Centre for Tuberculosis Control of Guangdong Province

Guangzhou, Guangdong, 510000, China

RECRUITING

Guangxi Center for Disease Prevention and Control

Nanning, Guangxi, 530000, China

RECRUITING

HeBei Province Center for Disease Prevention and Control

Shijiazhuang, Hebei, 050000, China

RECRUITING

Heilongjiang Province center for tuberculosis Control and Prevention

Haerbin, Heilongjiang, 150000, China

RECRUITING

Harbin Chest Hospital

Harbin, Heilongjiang, 150000, China

RECRUITING

Infectious Disease Prevention Hospital in Heilongjiang Province

Harbin, Heilongjiang, 150000, China

RECRUITING

The Infectious Hospital of Hebi

Hebi, Henan, 458000, China

RECRUITING

Kaifeng Pulmonary Disease Hospital

Kaifeng, Henan, 475000, China

RECRUITING

Sixth People's Hospital of Nanyang City

Nanyang, Henan, 473000, China

RECRUITING

The First Affiliated Hospital of Xinxiang Medical University

Xianxiang, Henan, 453100, China

RECRUITING

Wuhan medical treatment center

Wuhan, Hubei, 430000, China

RECRUITING

Wuhan Institute For Tuberculosis Control

Wuhan, Hubei, 430030, China

RECRUITING

Hunan Institute For Tuberculosis Control

Changsha, Hunan, 410000, China

RECRUITING

The Sixth People's Hospital of Nantong

Nantong, Jiangsu, 226000, China

RECRUITING

The Fifth People's Hospital of Suzhou

Suzhou, Jiangsu, 215000, China

RECRUITING

The Third People's Hospital of Zenjiang

Zhenjiang, Jiangsu, 212005, China

RECRUITING

Changchun Infectious Disease Hospital

Changchun, Jilin, 130000, China

RECRUITING

Tuberculosis Hospital in Jilin Province

Jilin, Jilin, 132000, China

RECRUITING

China Shenyang Chest Hospital

Shenyang, Jilin, 110000, China

RECRUITING

The Fourth People's Hospital of Ningxia Autonomous Region

Yinchuan, Ningxia, 750000, China

RECRUITING

The 4th People's Hospital of Qinghai Province

Xining, Qinghai, 810000, China

RECRUITING

The Infectious Disease Hospital of Wangkai Zaozhuang

Tengzhou, Shandong, 277500, China

RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

Taiyuan Fourth People's Hospital

Taiyuan, Shanxi, 030000, China

RECRUITING

The Tuberculosis Prevention and Treatment Hospital of Shanxi Province

Xi’an, Shanxi, 710100, China

RECRUITING

Public Health Clinical Center of Chengdu

Chengdu, Sichuan, 610061, China

RECRUITING

Tianjin Haihe Hospital

Tianjin, Tianjin Municipality, 300000, China

RECRUITING

Tianjin centers for Disease Control and Prevention

Tianjin, Tianjin Municipality, 300041, China

RECRUITING

Chest of Hospital of Xinjiang Uygur Autonomous Region of the PRC

Ürümqi, Xinjiang, 830001, China

RECRUITING

The Third People's Hospital of Kunming City

Kunming, Yunnan, 650041, China

RECRUITING

Related Publications (2)

• Gao M, Gao J, Du J, Liu Y, Zhang Y, Ma L, Mi F, Li L, Tang S; Trial Team. Efficacy of ultra-short course chemotherapy for new smear positive drug susceptible pulmonary tuberculosis: study protocol of a multicenter randomized controlled clinical trial. BMC Infect Dis. 2017 Jun 19;17(1):435. doi: 10.1186/s12879-017-2505-7.

  PMID: 28629333 DERIVED

• Pease C, Hutton B, Yazdi F, Wolfe D, Hamel C, Quach P, Skidmore B, Moher D, Alvarez GG. Efficacy and completion rates of rifapentine and isoniazid (3HP) compared to other treatment regimens for latent tuberculosis infection: a systematic review with network meta-analyses. BMC Infect Dis. 2017 Apr 11;17(1):265. doi: 10.1186/s12879-017-2377-x.

  PMID: 28399802 DERIVED

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

Isoniazid; Rifampin; Pyrazinamide; Ethambutol; Levofloxacin

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Pyrazines; Ethylenediamines; Diamines; Polyamines; Amines; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring

Study Officials

• Shenjie Tang, MD

  Beijing Chest Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shenjie Tang, MD

CONTACT

tangsj1106@sina.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, TB Department

Study Record Dates

• First Submitted: September 2, 2016
• First Posted: September 15, 2016
• Study Start: August 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: March 20, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (35)