Innovating(IN) Shorter(S), All- Oral, Precised(P), Individualized(I) Treatment Regimen(RE) for Rifampicin Resistant Tuberculosis(INSPIRE-TB)

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of a molecular drug-sensitivity test-guided individualized shorter all-oral regimen composed of 4-5 anti-tuberculosis drugs recommended by WHO in RRTB patients for 9-12 months in real-world practice, in some high RR-TB burden province of China. This study hopes to form a clinical pathway of all oral short-term treatment based on the guidance of rapid molecular drug sensitivity that can be popularized in China, and update the Chinese guidelines of RR-TB treatment management.

Detailed Description
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This trial is a multi-centre prospective observational cohort study. The purpose of this study is to evaluate an individualized 9-12 month all-oral regimen in RRTB patients confirmed by phenotypic or molecular rifampicin sensitivity test. A total of 3000 participants with a shorter all-oral regimen and receiving clinical care at study sites will be estimated. Drug resistance to RIF, FQs, SLIDs, INH, Eto and PZA was evaluated before enrollment. After screening for eligibility, treatment regimen is individually designed in this trial by responsible physicians at study sites based on radiological, clinical, bacteriological as well as drug sensitivity test results. Candidate anti-TB drugs are BDQ, LZD, FQs, Cs, Cfz, Z, Dlm and INH. Follow-up visits are conducted monthly until end of treatment. After end of treatment, follow-up visits were conducted every 3 months for the first 6 months and then every 6 months until 24 months after discontinuation. The primary objective is to evaluate end of treatment outcomes. Favorable outcomes include cured and treatment completed. Unfavorable outcomes include treatment failed, lost to follow-up and died. The secondary objective is to assess the median time to sputum culture conversion, frequency of and time to relapse and frequency of recurrence-free survival. Safety evaluations performed are the routine lab tests, blood glucose, hearing, vital signs, electrocardiograph (ECG), reporting of adverse events, physical examinations and chest CT. Adverse events will be monitored and promptly managed during the whole treatment course.

Official Title
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Innovating(IN) Shorter(S), All- Oral, Precised(P), Individualized(I) Treatment Regimen(RE) for Rifampicin Resistant Tuberculosis(INSPIRE-TB)

Conditions
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Multidrug Resistant Tuberculosis

Intervention / Treatment
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* Other: This is a non-intervention observational study.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient who are willing to participate and signs informed consent. Any patient with rifampicin resistant tuberculosis confirmed by phenotypic or molecular drug sensitivity test. Exclusion Criteria: Any regimen that does not conform to a shorter all-oral regimen composed of 4-5 drugs(BDQ, LZD, FQs, Cs, Cfz, Z, Dlm, INH). Combined extrapulmonary tuberculosis(except for tuberculous pleuritis, endobronchial tuberculosis and tubercular lymphadenitis).
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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Individualized 9-12 month all-oral regimen<br>Treatment regimen is individually designed in this trial by responsible physicians at study sites based on radiological, clinical, bacteriological as well as drug sensitivity test results. RIF resistance was confirmed with phenotypic or molecular drug sensitivity test. Drug resistance to FQs, SLIDs, INH and Eto was evaluated by GeneXpert MTB/XDR. PZA resistance was confirmed by whole genome sequencing. Candidate anti-TB drugs are BDQ, LZD, FQs, Cs, Cfz, Z, Dlm and INH. | Other: This is a non-intervention observational study.<br>* No applicable intervention. This is a secondary data analysis observational study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| End of treatment outcomes | End of treatment outcomes: cured, treatment completed, treatment failed, lost to follow-up, died and not evaluated. | At completion of 9-12 months treatment regimen | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The median time to Sputum Culture Conversion | Time from treatment initiation to the first of two consecutive negative sputum cultures without an intervening positive culture in liquid media. | At completion of 9-12 months treatment regimen | 
| Frequency of and time to relapse | Proportion of patients and time to relapse confirmed with radiological, clinical or bacteriological tests during treatment and post-treatment follow-up visits. | 2 years after end of treatment | 
| frequency of recurrence-free survival | Rate of patients who confirmed absence of radiological, clinical or bacteriological signs of TB post treatment follow-up visits. | 6 months, 1 year and 2 years after end of treatment | 
| The frequency of and time to grade 3 or greater adverse events | 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. | At completion of 9-12 months treatment regimen | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multidrug resistant tuberculosis, shorter treatment, all-oral regimen, PZA sensitivity