NCT02208427

Toward a Safe and Reachable Preventive Therapy for LTBI: a Multicenter Randomized Controlled Study in Taiwan

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 283 (actual)
• Sponsor: National Taiwan University Hospital · Academic / Other
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Latent Tuberculosis Infection

Interventions

Type	Name	Description
DRUG	Rifapentine and Isoniazid for 3 months	weekly oral Rifapentine 15 mg/kg plus Isoniazid 15 mg/kg for 12 doses
DRUG	Isoniazid for 9 months	daily oral Isoniazid 5 mg/kg for 9 months under supervision (conventional IPT)

Timeline

• Start date: 2014-08-01
• Primary completion: 2016-12-01
• Completion: 2016-12-01
• First posted: 2014-08-05
• Last updated: 2016-12-15

Locations

1 site across 1 country: Taiwan