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

Latent Tuberculosis Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02208427
• Other study ID #: 201309055MINC
• Status: Active, not recruiting
• Phase: Phase 3
• First received: July 31, 2014
• Last updated: December 14, 2016
• Start date: August 2014
• Est. completion date: December 2016

Study information

• Verified date: December 2016
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Ministry of Health and Welfare
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 283
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

Inclusion criteria:

• Household contacts of TB or TB contacts in schools or densely-populated institutes

• Age =12 year-old

• Index case having smear-positive pulmonary TB

• Contact with index case for >8 hours within single day or >40 hours within total transmissible period

• TST =10 mm within one month

• Born in 1986 or after (not applicable in the National Taiwan University Hospital Hsin-Chu branch and Chang-Hua Hospital)

Exclusion Criteria:

• 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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Latent Tuberculosis
• Latent Tuberculosis Infection
• Tuberculosis

Intervention

Drug:
• Rifapentine and Isoniazid for 3 months
weekly oral Rifapentine 15 mg/kg plus Isoniazid 15 mg/kg for 12 doses
• Isoniazid for 9 months
daily oral Isoniazid 5 mg/kg for 9 months under supervision (conventional IPT)

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	completion rate	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.	2 years	No
Secondary	side effect	To evaluate the side effect profile (especially hepatotoxicity, defined as AST and/or ALT =2 ULN) of the two preventive regimens	3 months in the 3M_RH group and 9 months in the 9M_INH group	Yes
Secondary	interruption	To calculate the number of participants with interruption in preventive therapy and to know the reasons of interruption by questionnaire	3 months in the 3M_RH group and 9 months in the 9M_INH group	No
Secondary	active TB	To know the rate of active TB within subsequent 2 years	2 years after enrollment	No