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

NCT04485156 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: Hi-DoRi-3
• Study Type: interventional
• Target: 926
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberculosis, Pulmonary

Keywords

Tuberculosis; Rifampicin; Treatment; Shortening

Outcome Measures

Primary Outcomes (1)

• Incidence of unfavorable treatment outcomes between two arms

  Within 18 months of randomization

Secondary Outcomes (6)

• 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

Study Arms (2)

Arm 1 (Conventional treatment group)

ACTIVE COMPARATOR

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; Drug: Pyrazinamide; Drug: Ethambutol; Drug: Rifampicin

Arm 2 (High-dose rifampicin group)

EXPERIMENTAL

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; Drug: Isoniazid; Drug: Pyrazinamide

Interventions

High-dose rifampicin DRUG

30mg/kg

Arm 2 (High-dose rifampicin group)

Isoniazid DRUG

300mg

Arm 1 (Conventional treatment group); Arm 2 (High-dose rifampicin group)

Pyrazinamide DRUG

20-30mg/kg

Arm 1 (Conventional treatment group); Arm 2 (High-dose rifampicin group)

Ethambutol DRUG

15-20mg/kg

Arm 1 (Conventional treatment group)

Rifampicin DRUG

10mg/kg

Arm 1 (Conventional treatment group)

Eligibility Criteria

• Age: 19 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (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, 110-744, South Korea

Location

Related Publications (2)

• Kwak N, Kim JY, Kim HJ, Kwon BS, Lee JH, Mok J, Kwon YS, Kang YA, Park Y, Lee JY, Jeon D, Lee JK, Yang JS, Whang J, Kim KJ, Kim YR, Cheon M, Park J, Hahn S, Yim JJ. High-Dose Rifampicin for 3 Months after Culture Conversion for Drug-Susceptible Pulmonary Tuberculosis. Tuberc Respir Dis (Seoul). 2025 Jan;88(1):170-180. doi: 10.4046/trd.2024.0099. Epub 2024 Sep 27.

  PMID: 39343425 DERIVED

• 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.

  PMID: 35978342 DERIVED

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Interventions

Rifampin; Isoniazid; Pyrazinamide; Ethambutol

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring; Pyrazines; Ethylenediamines; Diamines; Polyamines; Amines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2020
• First Posted: July 24, 2020
• Study Start: September 1, 2020
• Primary Completion: August 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 24, 2020

Record last verified: 2020-07

Locations

KR (1)