Treatment Shortening of Drug-Sensitive Pulmonary Tuberculosis Using High Dose Rifampicin (Hi-DoRi-3)

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effectiveness and safety of the regimen including high dose rifampicin for individualized duration (3 months after Culture Conversion) for the treatment of drug-sensitive pulmonary tuberculosis.

Official Title
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Treatment Shortening of Drug-Sensitive Pulmonary Tuberculosis Using High Dose Rifampicin to 3 Months After Culture Conversion (Hi-DoRi-3): A Phase 3, Multicenter, Randomized, Open-label, Clinical Trial

Conditions
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Tuberculosis, Pulmonary

Intervention / Treatment
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* Drug: High-dose rifampicin
* Drug: Isoniazid
* Drug: Pyrazinamide
* Drug: Ethambutol
* Drug: Rifampicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented positivity by sputum Xpert MTB/RIF assay Administration of current tuberculosis therapy (if any) for no more than 7 days (≤7) at the time of enrolment. Exclusion Criteria: Negative on Xpert MTB/RIF assay Resistance to rifampicin as detected by an Xpert MTB/RIF assay Known resistance to isoniazid, rifampicin, or pyrazinamide HIV positive Cancer patient on anti-cancer chemotherapy Uncontrolled DM Chronic hepatitis, liver cirrhosis Any contraindications of drugs to be used

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 85 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: Arm 1 (Conventional treatment group)<br>Will be treated as recommended by Korean Guidelines For Tuberculosis as well as WHO guidelines (e.g. isoniazid, rifampicin, ethambutol, and pyrazinamide for 2 months followed by isoniazid, rifampicin, (and ethambutol)) Duration of the treatment - 6 months in total | Drug: Isoniazid<br>* 300mg<br>Drug: Pyrazinamide<br>* 20-30mg/kg<br>Drug: Ethambutol<br>* 15-20mg/kg<br>Drug: Rifampicin<br>* 10mg/kg<br>|
| Experimental: Arm 2 (High-dose rifampicin group)<br>High-dose rifampicin, isoniazid, and pyrazinamide Rifampicin: 30mg/kg Isoniazid: 300mg/day Pyrazinamide: 1000mg/day (<50kg), 1500mg/day (50-70kg), 2000mg /day (>70kg), till culture conversion Duration of the treatment Till 12 weeks after culture conversion on liquid media | Drug: High-dose rifampicin<br>* 30mg/kg<br>Drug: Isoniazid<br>* 300mg<br>Drug: Pyrazinamide<br>* 20-30mg/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of unfavorable treatment outcomes between two arms |  | Within 18 months of randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to unfavorable treatment outcomes |  | Within 18 months of randomization | 
| Time to culture conversion on liquid media |  | Censored at 2 months of treatment | 
| Proportion of participants with treatment success |  | At the end of treatment | 
| Proportion of participants with relapse of same strain |  | At the end of study | 
| Time to relapse with same strain |  | through study completion, 18months after randomization | 
| Occurrence of AEs grade 3 and above |  | through study completion, 18months after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, Rifampicin, Treatment, Shortening