Clinical trial NCT01398618: Comparing Two Preventive Regimens for Latent Tuberculosis Infection (LTBI)
Official title: Comparing the Efficacy of Two Preventive Regimens for Adult Household Contacts With Latent Tuberculosis Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Latent Tuberculosis Infection
Keywords: latent tuberculosis infection
tuberculosis
interferon-gamma release assay
preventive therapy
9-month isoniazid
4-month rifampin
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2011-07-20
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

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

Primary outcomes:
measure: Number of Participants developing active tuberculosis
timeFrame: every 6 months for 2 years
Secondary outcomes:
measure: the sensitivity and specificity of tuberculin-skin-testing and QuantiFERON TB-Gold assay for the development of active pulmonary tuberculosis
timeFrame: Every 6 months for 2 years
Other outcomes:
Locations:
city: Tainan
country: Taiwan
facility: Chest Hospital, Department of Health, Executive Yuan
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Attending Physician
name: Jann-Yuan Wang, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: