Comparing Two Preventive Regimens for Latent Tuberculosis Infection (LTBI)

NCT ID: NCT01398618

Last Updated: 2011-07-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2013-12-31

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).

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).

Conditions

Latent Tuberculosis Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

4M-RMP

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

Group Type: EXPERIMENTAL

4-month rifampin vs. 9-month isoniazid

Intervention Type: DRUG

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.

9M-INH

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

Group Type: ACTIVE_COMPARATOR

4-month rifampin vs. 9-month isoniazid

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

4-month RMP vs. 9-month INH

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

National Taiwan University Hospital

Principal Investigators

Jann-Yuan Wang, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Attending Physician

Locations

Chest Hospital, Department of Health, Executive Yuan

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Countries

Taiwan

Related Links

http://www.ntuh.gov.tw/RECO

Website of Research Ethic Committee of National Taiwan University Hospital

Other Identifiers

201010017M

Identifier Type: -

Identifier Source: org_study_id