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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Tuberculosis, Pulmonary
• Intervention / Treatment: Drug: Isoniazid; Drug: Pyrazinamide; Drug: Ethambutol; Drug: Rifampicin; Drug: High-dose rifampicin

• Study Type: Interventional
• Enrollment (Anticipated): 926
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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: Isoniazid; 300mg; Drug: Pyrazinamide; 20-30mg/kg; Drug: High-dose rifampicin; 30mg/kg

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Pusan National University Hospital; Chonnam National University Hospital; Seoul National University Bundang Hospital; SMG-SNU Boramae Medical Center; Severance Hospital; Korean Center for Disease Control and Prevention; Pusan National University Yangsan Hospital; International Tuberculosis Research Center; National Medical Center, Seoul; Korean Institute of Tuberculosis

Publications and helpful links

General Publications

• Kwak N, Jeon D, Park Y, Kang YA, Kim KJ, Kim YR, Kwon BS, Kwon YS, Kim HJ, Lee JH, Lee JY, Lee JK, Mok J, Cheon M, Park J, Hahn S, Yim JJ. Treatment shortening of drug-sensitive pulmonary tuberculosis using high-dose rifampicin for 3 months after culture conversion (Hi-DoRi-3): a study protocol for an open-label randomized clinical trial. Trials. 2022 Aug 17;23(1):666. doi: 10.1186/s13063-022-06631-z.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): August 1, 2025
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: July 6, 2020
• First Submitted That Met QC Criteria: July 21, 2020
• First Posted (Actual): July 24, 2020

Study Record Updates

• Last Update Posted (Actual): July 24, 2020
• Last Update Submitted That Met QC Criteria: July 21, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Treatment; Tuberculosis; Rifampicin; Shortening
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Fatty Acid Synthesis Inhibitors; Rifampin; Isoniazid; Pyrazinamide; Ethambutol
• Other Study ID Numbers: Hi-DoRi-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No