1HP Versus 3HR in the Treatment of Tuberculosis Infection in Vietnam

NCT06191692 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: TBIshort
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 2

Brief Summary

Introduction: Tuberculosis (TB) infection is a key driver of the TB pandemic, with over 10.6 million people fell ill with TB disease in 2022. About one-quarter of the global population is estimated to be infected with TB bacteria. Around 5-10% of people with TB infection will develop active and contagious TB disease, which could be largely avoided if TB infection is identified and given effective preventative treatment, before progression to active disease. The long treatment of TB infection with regimens lasting from three to nine months is a significant barrier to treatment completion in individuals with a confirmed diagnosis of TB infection. Adapting a shorter regimen than the current regimens could lead to a higher treatment completion rate and increased uptake of preventative therapy for TB, as well as reduced side effects. Methods and analysis: An open-label, randomized clinical trial (1:1) will be performed in two study sites in Ha Noi, Vietnam (Vietnam National Lung Hospital and Ha Noi Lung Hospital). Adult household contacts (n=350) of people with new, bacteriologically-confirmed, pulmonary, drug-susceptible TB who initiate treatment will be invited to participate. Aim: To compare the TB preventive therapy completion rates and adverse event incidence between a new one-month regimen (1HP) versus the current three-month regimen (3HR)\*. \*1HP= one month of daily isoniazid (H/INH) and rifapentine (P/RPT) 3HR= three months of daily isoniazid (H/INH) and rifampicin (R/RIF)

Conditions

Tuberculosis Infection

Keywords

Tuberculosis; TB preventive therapy; Tuberculosis infection; Latent TB infection; LTBI; TBI

Outcome Measures

Primary Outcomes (1)

• 1. % Adequate adherence in each arm

  Adequate treatment adherence is defined as taking ≥90% of TB preventive therapy doses within the time frame. Treatment adherence will be recorded by both study schedule and programmatic adherence.

  From study entry at Week 0 through up to 16 weeks of 3HR (Arm A), or up to 6 weeks of 1HP (Arm B), to be reported at the end of the trial.

Secondary Outcomes (3)

• The incidence rate of severe adverse events among two arms.

  From study entry at Week 0 through up to 16 weeks of 3HR (Arm A), or up to 6 weeks of 1HP (Arm B)

• Comparison of adherence measured as the proportion of treatment taken in the regimens (1HP vs 3HR).

  From study entry at Week 0 through up to 16 weeks of 3HR (Arm A), or up to 6 weeks of 1HP (Arm B)

• The incidence rate of a targeted event of grade 3,4 or 5*** and one grade increase from the baseline among two arms.

  From study entry at Week 0 through up to 16 weeks of 3HR (Arm A), or up to 6 weeks of 1HP (Arm B)

Study Arms (2)

3 months of daily rifampicin plus isoniazid regimen (Arm A)

ACTIVE COMPARATOR

Participants will receive rifampicin (dosage based on their weight\*, 10mg/kg/day, maximum 600mg), 300 mg of isoniazid, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day from week 1 to week 12 for a total of 90 doses. \* Weight will be monitored and dosing adjusted as needed during treatment

Drug: Isoniazid; Drug: Rifampicin

1 month of daily rifapentine plus isoniazid regimen (Arm B)

EXPERIMENTAL

Participants will receive rifapentine (dosage based on their weight\* 300 mg daily for participants body weight of 30kg -\<35 kg, 450 mg daily for a weight of 35 to 45 kg, and 600 mg for a weight of \>=45 kg), 300 mg of isoniazid, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day from week 1 to week 4 for a total of 28 days. \* Weight will be monitored and dosing adjusted as needed during treatment

Drug: Isoniazid; Drug: Rifapentine

Interventions

Isoniazid DRUG

This randomized control trial will compare the treatment adherence and safety of the 1HP (Arm B) regimen and standard 3HR (Arm A) regimens for TB infection treatment

Also known as: INH

1 month of daily rifapentine plus isoniazid regimen (Arm B); 3 months of daily rifampicin plus isoniazid regimen (Arm A)

Rifapentine DRUG

This randomized control trial will compare the treatment adherence and safety of the 1HP (Arm B) regimen and standard 3HR (Arm A) regimens for TB infection treatment

Also known as: RPT

1 month of daily rifapentine plus isoniazid regimen (Arm B)

Rifampicin DRUG

This randomized control trial will compare the treatment adherence and safety of the 1HP (Arm B) regimen and standard 3HR (Arm A) regimens for TB infection treatment

Also known as: RIF

3 months of daily rifampicin plus isoniazid regimen (Arm A)

Eligibility Criteria

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

You may qualify if:

• Household contacts of people with new, bacteriologically-confirmed, pulmonary, drug-susceptible TB who initiated treatment with residence in the intervention areas;
• Positive QFT-Plus or TST results (TST induration of at least 5mm)
• Agree to remain in contact and provide updated information as necessary, and have no current plans to relocate outside the designed area for the duration of the study;
• Age ≥ 18 years;
• Capable of providing signed informed consent;
• Willing to participate in the study visits and procedures

You may not qualify if:

• Indeterminate results on QFT-Plus;
• Clinical or radiographic suspicions or history of previous active TB;
• Known hypersensitivity or contraindication to any components of the regimens;
• Weight \<30kg;
• Acute or chronic liver failure with elevated liver enzymes or evidence of liver dysfunction such as jaundice or a history of liver failure caused by isoniazid or rifampicin; History of liver cirrhosis at any time before study entry;
• Infection with suspected or confirmed tuberculosis strains resistant to isoniazid or rifampicin;
• Porphyria- Porphyrin metabolism disorder;
• Polyneuropathy (self-reported/ confirmed);
• Pregnant or planning to become pregnant within 120 days of enrollment;
• Any other severe underlying condition that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial;
• Participation in other clinical intervention trials or research protocols (participation in other studies that do not involve an intervention may be allowed, but this must be discussed and approved by the Chief Investigator).

Sponsors & Collaborators

• Freundeskreis Für Internationale Tuberkulosehilfe e.V: lead

Study Sites (2)

Vietnam National Lung Hospital

Hanoi, Hanoi, 10000, Vietnam

Location

Ha Noi Lung Hospital

Hà Nội, 10000, Vietnam

Location

MeSH Terms

Conditions

Latent Tuberculosis; Tuberculosis

Interventions

Isoniazid; rifapentine; Rifampin

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Han Nguyen, MD

CONTACT

+ 84945421868; han.nguyen@tbhelp.org

Study Design

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

Model Details: Households will be randomized in a 1:1 ratio to the two treatment groups (1HP/3HR) using cluster randomization

Study Record Dates

• First Submitted: December 20, 2023
• First Posted: January 5, 2024
• Study Start: August 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 19, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

VN (2)