Randomized Controlled Multi-center Short Course Treatment for Rifampicin Resistant Tuberculosis

Study Overview
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Brief Summary
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This study is a randomized, controlled, multi-center clinical study. The main purpose of this study was to study the efficacy and safety data of total oral short-term therapy as an alternative to injection in the treatment of newly diagnosed RR-TB patients.

Detailed Description
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A group: 4-6 INH EMB PZA Pto AM Cfz Mfx / 5 EMB PZA Cfz Mfx B group: 4-6 INH EMB PZA Pto LZD Cfz Mfx / 5 EMB PZA Cfz Mfx C group: 4-6 BDQ LZD MFX CS CFZ / 5MFX CS CFZ (INH: Isoniazid, EMB: Ethambutol, PZA: Pyrazinamide, Pto: Prothionamide, AM: Amikacin, Cfz: Clofazimine, Mfx: Moxifloxacin, LZD: Linezolid, BDQ: Bedaquiline, CS: Cycloserine) A group is the control group which includes injectable drugs (AM). B group and C group are the experimental groups which are total oral short-term therapy.

Official Title
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A Randomized, Controlled, Multi-center Clinical Trial of Short Course Treatment for Newly Diagnosed Rifampicin Resistant Tuberculosis

Conditions
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Tuberculosis

Intervention / Treatment
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* Drug: Total oral short-term therapy that includes linezolid, bedaquiline and/or cycloserine.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed informed consent and accepted follow-up; the age is between 18 and 65 years old, both male and female, including inpatients and outpatients; no use of anti tuberculosis drugs, or use of anti tuberculosis drugs less than 1 month; the results of molecular biology test confirmed rifampicin resistance or MDR-TB patients; chest CT examination confirmed pulmonary tuberculosis, pulmonary lesions, or cavity; premenopausal women had negative pregnancy urine test and agreed to use high-efficiency contraceptive measures during the study period. Exclusion Criteria: drug sensitivity test or molecular drug sensitivity results show that the drug resistance (except isoniazid) or any component of the drug has a history of allergy, or is taking any drug that is contraindicated to the drug in the short-term treatment program; severe renal insufficiency (creatinine clearance rate (CrCl) less than 30 ml / min). liver function impairment (ALT and / or AST level 3 times higher than the upper limit of laboratory reference value, if it is temporary increase, it can be included after treatment recovery); those who are unable to participate in or comply with the treatment and follow-up; Q-T interval > 450 millisecond; have a history of cardiovascular diseases or are suffering from such diseases as heart failure, hypertension (poor blood pressure control), arrhythmia or post myocardial infarction state; pregnant or lactating women; those who are unable to take oral drugs; those who are currently participating in other clinical trials; patients with HIV positive or active viral hepatitis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>4-6 INH EMB PZA Pto AM Cfz Mfx / 5 EMB PZA Cfz Mfx (INH: Isoniazid, EMB: Ethambutol, PZA: Pyrazinamide, Pto: Prothionamide, AM: Amikacin, Cfz: Clofazimine, Mfx: Moxifloxacin) A group is the control group which includes injectable drugs (AM). | Drug: Total oral short-term therapy that includes linezolid, bedaquiline and/or cycloserine.<br>* AM is the traditional anti-TB drugs. Linezolid, bedaquiline and/or cycloserine, that might have potential efficacy of replacing injectable anti-TB drugs, are included into the total oral short-term therapy, and replace AM.<br>|
| Experimental: B<br>4-6 INH EMB PZA Pto LZD Cfz Mfx / 5 EMB PZA Cfz Mfx (INH: Isoniazid, EMB: Ethambutol, PZA: Pyrazinamide, Pto: Prothionamide, LZD: Linezolid, Cfz: Clofazimine, Mfx: Moxifloxacin) B group is the experimental groups which is total oral short-term therapy. | Drug: Total oral short-term therapy that includes linezolid, bedaquiline and/or cycloserine.<br>* AM is the traditional anti-TB drugs. Linezolid, bedaquiline and/or cycloserine, that might have potential efficacy of replacing injectable anti-TB drugs, are included into the total oral short-term therapy, and replace AM.<br>|
| Experimental: C<br>4-6 BDQ LZD MFX CS CFZ / 5MFX CS CFZ (BDQ: Bedaquiline, LZD: Linezolid, Mfx: Moxifloxacin, CS: Cycloserine, Cfz: Clofazimine) C group is another experimental groups which is also total oral short-term therapy, and includes new anti-TB drugs: BDQ. | Drug: Total oral short-term therapy that includes linezolid, bedaquiline and/or cycloserine.<br>* AM is the traditional anti-TB drugs. Linezolid, bedaquiline and/or cycloserine, that might have potential efficacy of replacing injectable anti-TB drugs, are included into the total oral short-term therapy, and replace AM.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Culture of Mycobacterium tuberculosis in sputum. | Mycobacterium tuberculosis culture of sputum will be carried out every month to understand the negative conversion rate and time of sputum bacteria, and then to understand the cure rate of patients. The final aim is to understand the efficacy of the total oral short-term anti-tuberculosis regimen. | Through study completion, an average of 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse effect. | All the types and frequency of adverse reactions that related to anti-tuberculosis drug were collected. | Through study completion, an average of 1 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, rifampin resistant, oral, shorter.