Toward a Safe and Reachable Preventive Therapy for LTBI: a Multicenter Randomized Controlled Study in Taiwan
- Conditions
- Latent Tuberculosis Infection
- Interventions
- Registration Number
- NCT02208427
- Lead Sponsor
- National Taiwan University Hospital
- Brief Summary
Background:
Tuberculosis (TB) remains the most important infectious disease in the world. Keys to successful control of TB is rapid diagnosis, prompt treatment, as well as effective preventive therapy for contacts with latent TB infection (LTBI). Current methods for the diagnosis of LTBI are tuberculin skin test (TST) and interferon-gamma release assay (IGRA). For preventive therapy, the recommended regimens include daily isoniazid for 9 months and daily rifampicin for 4 months. By incorporating long-acting rifapentine, a new regimen combining weekly rifapentine and high-dose isoniazid for a total of 12 doses has been proven of equal potency and toxicity. However, the treatment completion rate is much higher in weekly treatment for 3 months than daily treatment for 9 months. It is reasonable that using rifapentine-based preventive therapy can markedly increase the completion rate. However, study is lacking, especially in Asia, the high endemic area of TB.
With the effort of all health care workers and public health personnel, the incidence of TB in Taiwan has gradually declined in recent 10 years. In order to maintain the trend of decreasing in incidence, preventive therapy for LTBI become more and more important. However, which is the best preventive regimen for LTBI is still unknown. Therefore, we conduct the prospective randomized multicenter studies to compare the treatment completion rate of two regimens in Taiwan. The first regimen is daily isoniazid for 9 months. The second is weekly rifapentine plus high-dose isoniazid for 3 months.
- Detailed Description
Background:
Tuberculosis (TB) remains the most important infectious disease in the world. Keys to successful control of TB is rapid diagnosis, prompt treatment, as well as effective preventive therapy for contacts with latent TB infection (LTBI). Current methods for the diagnosis of LTBI are tuberculin skin test (TST) and interferon-gamma release assay (IGRA). For preventive therapy, the recommended regimens include daily isoniazid for 9 months and daily rifampicin for 4 months. By incorporating long-acting rifapentine, a new regimen combining weekly rifapentine and high-dose isoniazid for a total of 12 doses has been proven of equal potency and toxicity. However, the treatment completion rate is much higher in weekly treatment for 3 months than daily treatment for 9 months. It is reasonable that using rifapentine-based preventive therapy can markedly increase the completion rate. However, study is lacking, especially in Asia, the high endemic area of TB.
With the effort of all health care workers and public health personnel, the incidence of TB in Taiwan has gradually declined in recent 10 years. In order to maintain the trend of decreasing in incidence, preventive therapy for LTBI become more and more important. However, which is the best preventive regimen for LTBI is still unknown. Therefore, we conduct the prospective randomized multicenter studies to compare the treatment completion rate of two regimens in Taiwan. The first regimen is daily isoniazid for 9 months. The second is weekly rifapentine plus high-dose isoniazid for 3 months.
Specific Aims:
1. Understanding which of the two preventive regimens has the highest completion rate under supervision.
2. Understanding the reasons of interruption in preventive therapy.
3. Comparing the side effect profile of the two preventive regimens in Taiwan.
Methods:
In this prospective multicenter study, we will enroll close contacts aged \>=12 with positive TST. Chest radiography and sputum studies, if necessary, will be performed to exclude active pulmonary TB. After performing baseline IGRA, participants will be randomized into 2 groups with different preventive regimens. The first regimen is daily isoniazid for 9 months. The second is weekly rifapentine plus high-dose isoniazid for 3 months. The primary outcome is treatment completion rate of the two preventive regimens. The secondary outcome is toxicity. All participant will be followed for 2 years and screen for the development of active pulmonary TB by chest radiography and sputum studies if necessary. The reasons for treatment incompletion will be recorded.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 283
Not provided
- Clinical or radiographic evidence of active TB
- Index case having culture-negative pulmonary TB
- Index case having Isoniazid or Rifampin-resistant TB
- Receiving medications with significant interactions with Isoniazid, Rifampin, or Rifapentine
- Allergy to Isoniazid, Rifampin, or Rifapentine
- Sero-positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Documented liver cirrhosis
- Human immunodeficiency virus (HIV) infection
- Receiving immunosuppressants
- Receiving biological agents
- Hemoglobin <8 g/dL
- Neutrophil <750000 /mL
- Total bilirubin >2.5 mg/dL
- Aspartic transaminase (AST) or alanine transaminase (ALT) >2 folds of upper limit of normal (ULN)
- Pregnant or breast-feeding
- Life expectancy <3 years
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 3M_RH Rifapentine and Isoniazid for 3 months Rifapentine and Isoniazid for 3 months: weekly oral rifapentine 15 mg/kg plus isoniazid 15 mg/kg for 12 doses 9M_INH Isoniazid for 9 months Isoniazid for 9 months: daily oral isoniazid 5 mg/kg for 9 months
- Primary Outcome Measures
Name Time Method completion rate 2 years This prospective randomized interventional study is aimed to assess the completion rate of two different preventive regimens for LTBI by intent-to-treat analysis. Interruption of preventive therapy due to any reasons will be considered as incompletion.
- Secondary Outcome Measures
Name Time Method active TB 2 years after enrollment To know the rate of active TB within subsequent 2 years
side effect 3 months in the 3M_RH group and 9 months in the 9M_INH group To evaluate the side effect profile (especially hepatotoxicity, defined as AST and/or ALT ≥2 ULN) of the two preventive regimens
interruption 3 months in the 3M_RH group and 9 months in the 9M_INH group To calculate the number of participants with interruption in preventive therapy and to know the reasons of interruption by questionnaire
Trial Locations
- Locations (1)
National Taiwan University Hospital
🇨🇳Taipei, Taiwan