Comparing Two Preventive Regimens for Latent Tuberculosis Infection (LTBI)

Sponsor

National Taiwan University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT01398618

Collaborator

(none)

300

Enrollment

Locations

Arms

Duration (Months)

150

Patients Per Site

4.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Though still an endemic area, the incidence of tuberculosis (TB) in Taiwan is decreasing in recent years. Further reduction in TB incidence, or even elimination should rely on treatment for LTBI. However, which is the cost-effective screening method or what is the cost-effective regimen in Taiwan is still unclear.

Therefore, the investigators designed this prospective study to follow up adult household contacts with LTBI for 2 years and compare the efficacy of 9-month isoniazid and 4-month rifampicin).

Condition or Disease	Intervention/Treatment	Phase
Latent Tuberculosis Infection	Drug: 4-month rifampin vs. 9-month isoniazid	Phase 3

Detailed Description

In countries with a low incidence of tuberculosis (TB), most new, active cases have occurred among persons who were once infected, contained this infection, and then later developed active TB. Therefore, identifying persons with latent Mycobacterium tuberculosis infection (LTBI) followed by preventive therapy is an important strategy in public health for TB elimination. Until this decade, the diagnosis of LTBI had been based on contact investigation and tuberculin skin testing (TST). However, false-positive results are not uncommon due to its cross-reactivity with the bacille Calmette-Guérin (BCG) vaccine and some species of non-tuberculosis mycobacteria (NTM), and false-negative results can occur in at least 20% in immunocompromised hosts.

With the application of M. tuberculosis-specific antigens, current interferon-gamma release assays (IGRAs) have been shown to have a better sensitivity and specificity than TST for detecting host response to M. tuberculosis. Therefore, current guidelines for the diagnosis and management of latent tuberculosis infection recommend using IGRA to replace TST. Reports from recent studies comparing the sensitivity, specificity and availability, as well as cost-effective analysis for both tests are inconclusive. The best way varies in different areas, cultures and facilities. Therefore, collecting local data would be very helpful for policy making in public health.

Several regimens have been used in treating LTBI, including 9-month isoniazid, 4-month rifampin, 2-month rifampin plus pyrazinamide, and 3-month isoniazid plus rifampin. Among the 4 regimens, 2-month rifampin plus pyrazinamide has been reported to associate with unacceptable hepatotoxicity and even mortality due to hepatic failure. Therefore, this regimen has now been abandoned in treating LTBI. The treatment completion rate, adverse events, and reduction in risk of developing active TB are similar in 3-month isoniazid plus rifampin as in 6-month Isoniazid. At present, 9-month isoniazid is still the most popular regimen for LTBI, because the toxicity is low, the drug interaction is seldom, and isoniazid has been used for many years. However, the long treatment duration seriously compromises the completion rate. By contrast, rifampin is safe, cheap and more acceptable. Recent studies, including cost-effective analysis, favor using 4-month rifampin in treating LTBI. However, the outcome in these studies is completion rate of preventive therapy, rather than the event of developing active TB. In addition, some use statistic modeling rather conducting a clinical trial.

Though still an endemic area, the incidence of TB in Taiwan is decreasing in recent years. Further reduction in TB incidence, or even elimination should rely on treatment for LTBI. However, which is the cost-effective screening method or what is the cost-effective regimen in Taiwan is still unclear.

Therefore, the investigators designed this prospective study to follow up adult household contacts with LTBI for 2 years and compare the efficacy of 9-month isoniazid and 4-month rifampicin).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Comparing the Efficacy of Two Preventive Regimens for Adult Household Contacts With Latent Tuberculosis Infection

Study Start Date :

May 1, 2011

Anticipated Primary Completion Date :

Dec 1, 2013

Anticipated Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 4M-RMP adult household contacts with latent tuberculosis infection receiving 4-month rifampicin preventive therapy	Drug: 4-month rifampin vs. 9-month isoniazid In the 4M-RMP group, enrolled subjects received 600 mg rifampin daily for 4 months. In the 9M-INH group, enrolled subjects received 300 mg isoniazid daily for 9 months. Other Names: 4-month RMP vs. 9-month INH
Active Comparator: 9M-INH adult household contact with latent tuberculosis infection receiving 9-month isoniazid preventive therapy	Drug: 4-month rifampin vs. 9-month isoniazid In the 4M-RMP group, enrolled subjects received 600 mg rifampin daily for 4 months. In the 9M-INH group, enrolled subjects received 300 mg isoniazid daily for 9 months. Other Names: 4-month RMP vs. 9-month INH

Arm

Intervention/Treatment

Experimental: 4M-RMP

adult household contacts with latent tuberculosis infection receiving 4-month rifampicin preventive therapy

Drug: 4-month rifampin vs. 9-month isoniazid

In the 4M-RMP group, enrolled subjects received 600 mg rifampin daily for 4 months. In the 9M-INH group, enrolled subjects received 300 mg isoniazid daily for 9 months.

Other Names:

4-month RMP vs. 9-month INH

Active Comparator: 9M-INH

adult household contact with latent tuberculosis infection receiving 9-month isoniazid preventive therapy

Drug: 4-month rifampin vs. 9-month isoniazid

In the 4M-RMP group, enrolled subjects received 600 mg rifampin daily for 4 months. In the 9M-INH group, enrolled subjects received 300 mg isoniazid daily for 9 months.

Other Names:

4-month RMP vs. 9-month INH

Outcome Measures

Primary Outcome Measures

Number of Participants developing active tuberculosis [every 6 months for 2 years]

Secondary Outcome Measures

the sensitivity and specificity of tuberculin-skin-testing and QuantiFERON TB-Gold assay for the development of active pulmonary tuberculosis [Every 6 months for 2 years]
Sensitivity: No. of participants who were test-positive among all participants who developed active pulmonary tuberculosis Specificity: No. of participants who were test-negative among all participants who did not develop active pulmonary tuberculosis

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

household contact of patients with newly diagnosed, culture-confirmed pulmonary tuberculosis
age > 18
tuberculin skin testing-positive or QuantiFERON-positive
hemoglobin > 8 g/dL
neutrophil > 750 /uL
total bilirubin < 2.5 mg/dL
aspartic and alanine transaminases < 2 times of upper limit of normal
willing to receive serology tests for HBV and HCV infection
no history of allergy to isoniazid and rifampin
not currently pregnant or breast-feeding

Exclusion Criteria:

the M. tuberculosis isolate of the index case were isoniazid- or rifampin-resistant
liver cirrhosis
clinical or radiographical evidence of active tuberculosis
active hepatitis
currently receiving medication that have documented drug interaction with isoniazid or rifampin
life expectancy < 3 years