Latent Tuberculosis InfectionPhase 3NCT01398618
Comparing Two Preventive Regimens for Latent Tuberculosis Infection (LTBI)
A Phase 3 study testing 4-month rifampin vs. 9-month isoniazid in people with Latent Tuberculosis Infection, run by National Taiwan University Hospital at 2 sites in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Latent Tuberculosis Infection
- What is being tested?
- 4-month rifampin vs. 9-month isoniazid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 2 sitesTaiwan
- Study dates
- May 2011to Dec 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
Taiwan2 sites
Chest Hospital, Department of Health, Executive Yuan
Tainan, 71742
National Taiwan University Hospital
Taipei, 100
About this study
Official title: Comparing the Efficacy of Two Preventive Regimens for Adult Household Contacts With Latent Tuberculosis Infection
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).
Read the 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
- Being tested
- 4-month rifampin vs. 9-month isoniazid
- Keywords
- latent tuberculosis infection, tuberculosis, interferon-gamma release assay, preventive therapy, 9-month isoniazid, 4-month rifampin
- Medical subject headings
- Latent Tuberculosis, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4-month rifampin vs. 9-month isoniazidDrug
Also called 4-month RMP vs. 9-month INH
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.
| Study group | Role | What they receive |
|---|---|---|
| 4M-RMP | Experimental | adult household contacts with latent tuberculosis infection receiving 4-month rifampicin preventive therapy Receives: Drug: 4-month rifampin vs. 9-month isoniazid |
| 9M-INH | Active comparator | adult household contact with latent tuberculosis infection receiving 9-month isoniazid preventive therapy Receives: Drug: 4-month rifampin vs. 9-month isoniazid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants developing active tuberculosis
Measured: every 6 months for 2 years
Secondary outcomes (1)
the sensitivity and specificity of tuberculin-skin-testing and QuantiFERON TB-Gold assay for the development of active pulmonary tuberculosis
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
Measured: Every 6 months for 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2011 (estimated)
- Study startMay 2011
- Primary completionDec 2013 (estimated)
- Study completionDec 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Latent Tuberculosis InfectionStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Jann-Yuan Wang, Ph.D., Principal investigator, Attending Physician
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01398618
- Sponsor's protocol ID
- 201010017M
- Status last verified
- Jun 2011
- First submitted
- 1 Jul 2011
- Last updated
- 20 Jul 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparing the Efficacy of Two Preventive Regimens for Adult Household Contacts With Latent Tuberculosis Infection
- ClinicalTrials.gov ID
- NCT01398618
- Acronym / sponsor ID
- 201010017M
- Conditions
- Latent Tuberculosis Infection
- Keywords
- latent tuberculosis infection, tuberculosis, interferon-gamma release assay, preventive therapy, 9-month isoniazid, 4-month rifampin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 20 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 4M-RMP | Experimental | Drug: 4-month rifampin vs. 9-month isoniazidadult household contacts with latent tuberculosis infection receiving 4-month rifampicin preventive therapy |
| 9M-INH | Active comparator | Drug: 4-month rifampin vs. 9-month isoniazidadult household contact with latent tuberculosis infection receiving 9-month isoniazid preventive therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4-month rifampin vs. 9-month isoniazidAlso: 4-month RMP vs. 9-month INHIn 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. | Drug | 4M-RMP, 9M-INH |
Primary outcome
Number of Participants developing active tuberculosis
Time frame: every 6 months for 2 years
1 secondary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2011.
- Website of Research Ethic Committee of National Taiwan University HospitalLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jann-Yuan Wang, Ph.D. principal investigator
Attending Physician
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 4-month rifampin vs. 9-month isoniazid in people with Latent Tuberculosis Infection, run by National Taiwan University Hospital at 2 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Jul 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants developing active tuberculosis (time frame: every 6 months for 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2011; AzTrials last refreshed its copy on 31 Oct 2026.