Comparing Two Preventive Regimens for Latent Tuberculosis Infection (LTBI)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by National Taiwan University Hospital.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01398618
First received: July 1, 2011
Last updated: July 19, 2011
Last verified: June 2011
  Purpose

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 Intervention Phase
Latent Tuberculosis Infection
Drug: 4-month rifampin vs. 9-month isoniazid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Comparing the Efficacy of Two Preventive Regimens for Adult Household Contacts With Latent Tuberculosis Infection

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Number of Participants developing active tuberculosis [ Time Frame: every 6 months for 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • the sensitivity and specificity of tuberculin-skin-testing and QuantiFERON TB-Gold assay for the development of active pulmonary tuberculosis [ Time Frame: Every 6 months for 2 years ] [ Designated as safety issue: No ]

    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



Estimated Enrollment: 300
Study Start Date: May 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 4-month RMP vs. 9-month INH

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01398618

Locations
Taiwan
Chest Hospital, Department of Health, Executive Yuan
Tainan, Taiwan, 71742
National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Jann-Yuan Wang, Ph.D. Attending Physician
  More Information

Additional Information:
No publications provided

Responsible Party: Wang, Jann-Yuan/Attending Physician, National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01398618     History of Changes
Other Study ID Numbers: 201010017M
Study First Received: July 1, 2011
Last Updated: July 19, 2011
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
latent tuberculosis infection
tuberculosis
interferon-gamma release assay
preventive therapy
9-month isoniazid
4-month rifampin

Additional relevant MeSH terms:
Tuberculosis
Latent Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Isoniazid
Rifampin
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Lipid Regulating Agents
Antibiotics, Antitubercular
Enzyme Inhibitors
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014