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Trial record 1 of 2 for:    TB-TRUST
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Refining MDR-TB Treatment (T) Regimens (R) for Ultra(U) Short(S) Therapy(T) (TB-TRUST)

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ClinicalTrials.gov Identifier: NCT03867136
Recruitment Status : Recruiting
First Posted : March 7, 2019
Last Update Posted : July 23, 2020
Sponsor:
Information provided by (Responsible Party):
Wen-hong Zhang, Huashan Hospital

Brief Summary:
The purpose of this study is to assess the efficacy, safety and tolerability of a combination of levofloxacin, linezolid, cycloserine and pyrazinamide (or clofazimine if resistant to pyrazinamide) treatments for 24 to 32 weeks (regimen consisted of clofazimine for 36~44 weeks) in subjects with multidrug-resistant tuberculosis (MDR-TB) compared to WHO standardized shorter regimen of 36-44 weeks.

Condition or disease Intervention/treatment Phase
Multidrug Resistant Tuberculosis Drug: PZA sensitivity guided ultra-short all Oral Regimen Drug: Standardized Shorter Regimen Not Applicable

Detailed Description:

The TB-TRUST is a phaseIII, multicenter, open-label, randomized controlled trial. The purpose of this study is to assess the feasibility of the ultra-short treatment regimen of all-oral anti-TB drugs among selected MDR-TB patients who are susceptible to fluoroquinolones.

A total of 354 participants with MDR-TB will be recruited and followed up until 84 weeks after randomization. During randomization, eligible patients will be assigned to in a 1:1 ratio to one of the following groups: The WHO standardized shorter regimen group and a PZA sensitivity guided ultra-short regimen group.

WHO standardized shorter regimen group consists of 36-44 weeks with two phases of treatment. The first is an intensive phase of 16 weeks (extended up a maximum of 20 or 24 weeks in case of lack of smear conversion at the end of 16 or 20 weeks), and included moxifloxacin, amikacin, prothionamide, pyrazinamide, high-dose isoniazid, ethambutol, and clofazimine. This is followed by a continuation phase of 20 weeks with the following agents: moxifloxacin, pyrazinamide, ethambutol, and clofazimine.

The PZA sensitivity guided ultra-short regimen consists of two periods of 24-36 weeks. During the first 4-8 weeks (waiting for pyrazinamide drug sensitivity test), the regimen consists of levofloxacin, linezolid, cycloserine, pyrazinamide, and clofazimine. Then based on molecular PZA drug sensitivity results, patients will be in divided into two sub-groups: pyrazinamide-susceptible (PZA-S) patients and pyrazinamide-resistant (PZA-R) patients. The Regimen for PZA-S patients, consisting of levofloxacin, linezolid, cycloserine, and pyrazinamide, are given until the 24th week (prolonged to 28 or 32 weeks if no smear conversion by end of 16th and 20th week). PZA-R sub-group regimen, consisting of levofloxacin, linezolid, cycloserine, and clofazimine given until 36th week (prolonged to 40 or 44 weeks if no smear conversion by end of 16th and 20th week)

The primary objective is to compare the treatment success rate without relapse between the WHO standardized shorter regimen group and the PZA sensitivity guided ultra-short regimen group.

The secondary objective is to compare the median time to sputum culture conversion. Safety evaluations performed are the routine lab tests, blood glucose, hearing, vital signs, electrocardiograph (ECG), reporting of adverse events, peripheral neuropathy brief examining with the use of a Brief Peripheral Neuropathy rating scale(BPNS) and ophthalmologic examination, including assessment of visual acuity and color vision,physical examinations and chest CT. Adverse events will be monitored and promptly managed during the whole treatment course.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 354 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Refining Multidrug Tuberculosis Treatment With the Ultra Short All Oral Regimen
Actual Study Start Date : June 1, 2020
Estimated Primary Completion Date : December 1, 2021
Estimated Study Completion Date : December 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
Experimental: PZA sensitivity guided ultra-short all Oral Regimen
The PZA sensitivity guided ultra-short regimen consists of two periods of 24-36 weeks. During the first 4-8 weeks(waiting for pyrazinamide drug sensitivity test), the regimen consists of levofloxacin, linezolid, cycloserine, pyrazinamide, and clofazimine. Then based on molecular PZA drug sensitivity results, patients will be in divided into two sub-groups: pyrazinamide-susceptible (PZA-S) patients and pyrazinamide-resistant (PZA-R) patients. The Regimen for PZA-S patients, consisting of levofloxacin, linezolid, cycloserine, and pyrazinamide, are given until the 24th week (prolonged to 28 or 32 weeks if no smear conversion by end of 16th and 20th week). PZA-R sub-group regimen, consisting of levofloxacin, linezolid, cycloserine, and clofazimine given until 36th week (prolonged to 40 or 44 weeks if no smear conversion by end of 16th and 20th week)
Drug: PZA sensitivity guided ultra-short all Oral Regimen
Pyrazinamide 1500 mg daily; Levofloxacin ≤50kg 500 mg daily, >50kg 750mg daily; Linezolid: 600 mg daily; Cycloserine ≤50kg 500 mg daily, >50kg 750mg daily; Clofazimine 100 mg daily; All treatment is taken daily;

Active Comparator: Standardized Shorter Regimen
WHO standardized shorter regimen group consists of 36-44 weeks with two phases of treatment. The first is an intensive phase of 16 weeks (extended up a maximum of 20 or 24 weeks in case of lack of smear conversion at the end of 16 or 20 weeks), and included moxifloxacin, amikacin, prothionamide, pyrazinamide, high-dose isoniazid, ethambutol and clofazimine. This is followed by a continuation phase of 20 weeks with the following agents: moxifloxacin, pyrazinamide, ethambutol and clofazimine.
Drug: Standardized Shorter Regimen
Pyrazinamide 1500 mg daily;Levofloxacin 400 mg daily,; Prothionamide ≤50kg 500 mg daily, >50kg 750mg daily; Ethambutol: ≤50kg 750 mg daily, >50kg 1000mg daily; Clofazimine: 100 mg daily; Amikacin 600mg daily; High-dose isoniazid 600mg daily. All treatment is taken daily.




Primary Outcome Measures :
  1. Treatment success rate of the ultra short regimen [ Time Frame: 84 weeks after randomization. ]
    To compare the treatment success rate without relapse between the PZA sensitivity guided all oral ultra short regimen group and the WHO standardized shorter regimen group. Treatment outcomes will be classified into favourable outcome and unfavourble outcome.


Secondary Outcome Measures :
  1. The median time to Sputum Culture Conversion [ Time Frame: 12-36 weeks after treatment initiation ]
    time from treatment initiation to the first of two consecutive negative sputum cultures without an intervening positive culture in liquid media between the ultra short regimen group and the standardized short regimen group;

  2. The frequency of grade 3 or greater adverse events among patients treated with the ultra short regimen [ Time Frame: 84 weeks after treatment initiation ]
    to compare the proportion of patients who experience grade 3 or greater adverse events (graded according to the Division of AIDS severity criteria for adverse events), during treatment or follow-up, on the experimental regimen when compared to the control regimen;



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

1.Willing to participate in trial treatment and follow-up and can give informed consent 2.18-70 years old 3.Has smear-positive pulmonary tuberculosis with initial laboratory results with resistance to rifampicin confirmed by GeneXpert 4.Willing to carry out HIV testing. 5. If you are a non-menopausal woman, agree to use or have used effective contraception during treatment.

6. Have an identifiable address and stay in the area during the study period. 7.Willing to follow the follow-up study procedure after the follow-up.

Exclusion Criteria:

  1. Molecular drug resistance test for infected strains resistant to second-line injection;
  2. Molecular drug resistance assay for infected strains resistant to fluoroquinolone;
  3. Combined extrapulmonary tuberculosis;
  4. HIV antibody positive and AIDS patients;
  5. Critically ill patients, and according to the judgment of the research physician, it is impossible to survive for more than 16 weeks;
  6. Known to be pregnant or breastfeeding;
  7. Unable to attend or follow treatment or follow-up time;
  8. Can not take oral medications;
  9. Patients with impaired liver function (hepatic encephalopathy, ascites; total bilirubin is more than 2 times higher than the upper limit of normal; ALT or AST is more than 5 times the upper limit of normal);
  10. Blood muscle spasm is more than 1.5 times the upper limit of normal;
  11. The investigator believes that there are any social or medical conditions that expose the subject to a safety hazard;
  12. Simultaneously apply the drugs (glucocorticoids, interferons) that affect the efficacy of this study; and apply the following drugs contraindicated with the study drug, including non-steroidal anti-inflammatory drugs, monoamine oxidase inhibitors (phenethyl hydrazine, different Carbofurs et al), direct or indirect sympathomimetic drugs (such as pseudoephedrine), vasopressor drugs (such as adrenaline, norepinephrine), dopamine drugs (such as dopamine, dobutamine), 5 a serotonin reuptake inhibitor, a tricyclic antidepressant, a serotonin 5-HTI receptor antagonist (amitriptyline), meperidine or buspirone.
  13. Being allergic or intolerant of any study drug;
  14. Currently participating in another drug clinical trial;
  15. QTc interval ≥ 500 milliseconds during screening;
  16. Hemoglobin is less than 90g/L or platelet is less than 75*10^9/L;
  17. Have epilepsy, severe depression, irritability or psychosis;
  18. Alchol abuse(drinking more than 64g of ethanol a day for male, 42g for female).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03867136


Contacts
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Contact: Feng Sun, Dr. (086)15921403893 aaronsf1125@126.com
Contact: Yang Li, Dr (086)18817583793 y_li11@fudan.edu.cn

Locations
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China, Guangzhou
The Third People's Hospital of Shenzhen City Recruiting
Shenzhen, Guangzhou, China
Contact: Guofang Deng       lalaliy@sina.com   
China, Guizhou
Guiyang Public Health Treatment Center Recruiting
Guizhou, Guizhou, China
Contact: Cui Cai         
China, Henan
The Sixth People's Hospital of Zhengzhou Recruiting
Zhengzhou, Henan, China
Contact: Yu Chen       chenyuhnzz@163.com   
China, Hunan
Hunan Chest Hospital Recruiting
Changsha, Hunan, China
Contact: Liqiong Bai         
China, Jiangsu
Xuzhou Infectious Disease Hospital Recruiting
Xuzhou, Jiangsu, China
Contact: Le Peng         
China, Shanghai
Huashan Hospital of Fudan University Active, not recruiting
Shanghai, Shanghai, China, 200040
China, Shanxi
Shanxi Provincial Tuberculosis Control Institute Recruiting
Xi'an, Shanxi, China
Contact: Qianhong Wu         
China, Sichuan
Southwest Medical University Affiliated Hospital Recruiting
Luzhou, Sichuan, China
Contact: Fuli Huang         
China, Xinjiang
Chest Hospitalof Xinjiang Uygur Autonomous Region of PRC Recruiting
Urumqi, Xinjiang, China
Contact: Wenlong Guan       18999918582@189.cn   
China, Zhejiang
Hangzhou Red Cross Hospital Recruiting
Hangzhou, Zhejiang, China
Contact: Qingshan Cai       caiqs66@163.com   
Hangzhou Red Cross Hospital Recruiting
Hangzhou, Zhejiang, China
Contact: Yunfeng Sheng       shengyf617@163.com   
Zhejiang Provincial Center for Disease Control and Prevention Recruiting
Hangzhou, Zhejiang, China
Contact: Xiaomeng Wang         
The Central Hospital of Wenzhou City Recruiting
Wenzhou, Zhejiang, China
Contact: Jichan Shi       shijichan@163.com   
China
Jiangxi Chest Hospital Recruiting
Nanchang, China
Contact: Yuqing Wu         
Sponsors and Collaborators
Huashan Hospital
Investigators
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Principal Investigator: Wenhong Zhang, PhD Huashan Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Wen-hong Zhang, Director of Division of Infectious Diseases, Huashan Hospital
ClinicalTrials.gov Identifier: NCT03867136    
Other Study ID Numbers: KY2018-331
First Posted: March 7, 2019    Key Record Dates
Last Update Posted: July 23, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Wen-hong Zhang, Huashan Hospital:
Multidrug resistant tuberculosis
shorter treatment
all-oral regimen
Additional relevant MeSH terms:
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Tuberculosis
Tuberculosis, Multidrug-Resistant
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections