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

Sponsor

Seoul National University Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04485156

Collaborator

Chonnam National University Hospital (Other), National Medical Center, Seoul (Other), Pusan National University Hospital (Other), Pusan National University Yangsan Hospital (Other), Seoul National University Bundang Hospital (Other), SMG-SNU Boramae Medical Center (Other), Severance Hospital (Other), Korean Institute of Tuberculosis (Other), International Tuberculosis Research Center (Other), Korean Center for Disease Control and Prevention (Other)

926

Enrollment

Location

Arms

Anticipated Duration (Months)

12.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis, Pulmonary	Drug: High-dose rifampicin Drug: Isoniazid Drug: Pyrazinamide Drug: Ethambutol Drug: Rifampicin	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

926 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2020

Anticipated Primary Completion Date :

Aug 1, 2025

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1 (Conventional treatment group) 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 300mg Drug: Pyrazinamide 20-30mg/kg Drug: Ethambutol 15-20mg/kg Drug: Rifampicin 10mg/kg
Experimental: Arm 2 (High-dose rifampicin group) 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 30mg/kg Drug: Isoniazid 300mg Drug: Pyrazinamide 20-30mg/kg

Arm

Intervention/Treatment

Active Comparator: Arm 1 (Conventional treatment group)

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

300mg

Drug: Pyrazinamide

20-30mg/kg

Drug: Ethambutol

15-20mg/kg

Drug: Rifampicin

10mg/kg

Experimental: Arm 2 (High-dose rifampicin group)

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

30mg/kg

Drug: Isoniazid

300mg

Drug: Pyrazinamide

20-30mg/kg

Outcome Measures

Primary Outcome Measures

Incidence of unfavorable treatment outcomes between two arms [Within 18 months of randomization]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine	Seoul		Korea, Republic of	110-744