Latent Tuberculosis InfectionPhase 3NCT02208427
Toward a Safe and Reachable Preventive Therapy for LTBI: a Multicenter Randomized Controlled Study in Taiwan
A Phase 3 study testing Rifapentine and Isoniazid for 3 months and Isoniazid for 9 months in people with Latent Tuberculosis Infection, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
Background: Tuberculosis (TB) remains the most important infectious disease in the world. Keys to successful control of TB is rapid diagnosis, prompt treatment, as well as effective preventive therapy for contacts with latent TB infection (LTBI). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Latent Tuberculosis Infection
- What is being tested?
- Rifapentine and Isoniazid for 3 months and Isoniazid for 9 months
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 283 participants
- Where
- 1 siteTaiwan
- Study dates
- Aug 2014to Dec 2016
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Household contacts of TB or TB contacts in schools or densely-populated institutes
- Age ≥12 year-old
- Index case having smear-positive pulmonary TB
- Contact with index case for >8 hours within single day or >40 hours within total transmissible period
- TST ≥10 mm within one month
- Born in 1986 or after (not applicable in the National Taiwan University Hospital Hsin-Chu branch and Chang-Hua Hospital)
Who cannot join
- Clinical or radiographic evidence of active TB
- Index case having culture-negative pulmonary TB
- Index case having Isoniazid or Rifampin-resistant TB
- Receiving medications with significant interactions with Isoniazid, Rifampin, or Rifapentine
- Allergy to Isoniazid, Rifampin, or Rifapentine
- Sero-positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
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- Documented liver cirrhosis
- Human immunodeficiency virus (HIV) infection
- Receiving immunosuppressants
- Receiving biological agents
- Hemoglobin <8 g/dL
- Neutrophil <750000 /mL
- Total bilirubin >2.5 mg/dL
- Aspartic transaminase (AST) or alanine transaminase (ALT) >2 folds of upper limit of normal (ULN)
- Pregnant or breast-feeding
- Life expectancy <3 years
Trial locations and contacts
1 site in 1 country.
About this study
Background:
Tuberculosis (TB) remains the most important infectious disease in the world. Keys to successful control of TB is rapid diagnosis, prompt treatment, as well as effective preventive therapy for contacts with latent TB infection (LTBI). Current methods for the diagnosis of LTBI are tuberculin skin test (TST) and interferon-gamma release assay (IGRA). For preventive therapy, the recommended regimens include daily isoniazid for 9 months and daily rifampicin for 4 months. By incorporating long-acting rifapentine, a new regimen combining weekly rifapentine and high-dose isoniazid for a total of 12 doses has been proven of equal potency and toxicity. However, the treatment completion rate is much higher in weekly treatment for 3 months than daily treatment for 9 months. It is reasonable that using rifapentine-based preventive therapy can markedly increase the completion rate. However, study is lacking, especially in Asia, the high endemic area of TB.
With the effort of all health care workers and public health personnel, the incidence of TB in Taiwan has gradually declined in recent 10 years. In order to maintain the trend of decreasing in incidence, preventive therapy for LTBI become more and more important. However, which is the best preventive regimen for LTBI is still unknown. Therefore, we conduct the prospective randomized multicenter studies to compare the treatment completion rate of two regimens in Taiwan. The first regimen is daily isoniazid for 9 months. The second is weekly rifapentine plus high-dose isoniazid for 3 months.
Read the detailed description
Background:
Tuberculosis (TB) remains the most important infectious disease in the world. Keys to successful control of TB is rapid diagnosis, prompt treatment, as well as effective preventive therapy for contacts with latent TB infection (LTBI). Current methods for the diagnosis of LTBI are tuberculin skin test (TST) and interferon-gamma release assay (IGRA). For preventive therapy, the recommended regimens include daily isoniazid for 9 months and daily rifampicin for 4 months. By incorporating long-acting rifapentine, a new regimen combining weekly rifapentine and high-dose isoniazid for a total of 12 doses has been proven of equal potency and toxicity. However, the treatment completion rate is much higher in weekly treatment for 3 months than daily treatment for 9 months. It is reasonable that using rifapentine-based preventive therapy can markedly increase the completion rate. However, study is lacking, especially in Asia, the high endemic area of TB.
With the effort of all health care workers and public health personnel, the incidence of TB in Taiwan has gradually declined in recent 10 years. In order to maintain the trend of decreasing in incidence, preventive therapy for LTBI become more and more important. However, which is the best preventive regimen for LTBI is still unknown. Therefore, we conduct the prospective randomized multicenter studies to compare the treatment completion rate of two regimens in Taiwan. The first regimen is daily isoniazid for 9 months. The second is weekly rifapentine plus high-dose isoniazid for 3 months.
Specific Aims:
- Understanding which of the two preventive regimens has the highest completion rate under supervision.
- Understanding the reasons of interruption in preventive therapy.
- Comparing the side effect profile of the two preventive regimens in Taiwan.
Methods:
In this prospective multicenter study, we will enroll close contacts aged >=12 with positive TST. Chest radiography and sputum studies, if necessary, will be performed to exclude active pulmonary TB. After performing baseline IGRA, participants will be randomized into 2 groups with different preventive regimens. The first regimen is daily isoniazid for 9 months. The second is weekly rifapentine plus high-dose isoniazid for 3 months. The primary outcome is treatment completion rate of the two preventive regimens. The secondary outcome is toxicity. All participant will be followed for 2 years and screen for the development of active pulmonary TB by chest radiography and sputum studies if necessary. The reasons for treatment incompletion will be recorded.
- Conditions
- Latent Tuberculosis Infection
- Being tested
- Rifapentine and Isoniazid for 3 months, Isoniazid for 9 months
- Keywords
- isoniazid, LTBI, rifapentine, TST
- Medical subject headings
- Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rifapentine and Isoniazid for 3 monthsDrug
Also called Priftin, Isoniazid
weekly oral Rifapentine 15 mg/kg plus Isoniazid 15 mg/kg for 12 doses
Isoniazid for 9 monthsDrug
Also called Isoniazid
daily oral Isoniazid 5 mg/kg for 9 months under supervision (conventional IPT)
| Study group | Role | What they receive |
|---|---|---|
| 3M_RH | Experimental | Rifapentine and Isoniazid for 3 months: weekly oral rifapentine 15 mg/kg plus isoniazid 15 mg/kg for 12 doses Receives: Drug: Rifapentine and Isoniazid for 3 months |
| 9M_INH | Active comparator | Isoniazid for 9 months: daily oral isoniazid 5 mg/kg for 9 months Receives: Drug: Isoniazid for 9 months |
What is being measured
The primary outcome is the main question the study is designed to answer.
completion rate
This prospective randomized interventional study is aimed to assess the completion rate of two different preventive regimens for LTBI by intent-to-treat analysis. Interruption of preventive therapy due to any reasons will be considered as incompletion.
Measured: 2 years
Secondary outcomes (3)
side effect
To evaluate the side effect profile (especially hepatotoxicity, defined as AST and/or ALT ≥2 ULN) of the two preventive regimens
Measured: 3 months in the 3M_RH group and 9 months in the 9M_INH group
interruption
To calculate the number of participants with interruption in preventive therapy and to know the reasons of interruption by questionnaire
Measured: 3 months in the 3M_RH group and 9 months in the 9M_INH group
active TB
To know the rate of active TB within subsequent 2 years
Measured: 2 years after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2014 (estimated)
- Study startAug 2014
- Primary completionDec 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 283 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jann-Yuan Wang, MD. PhD., Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02208427
- Sponsor's protocol ID
- 201309055MINC
- Status last verified
- Dec 2016
- First submitted
- 31 Jul 2014
- Last updated
- 15 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Sun HY, Huang YW, Huang WC, Chang LY, Chan PC, Chuang YC, Ruan SY, Wang JY, Wang JT. Twelve-dose weekly rifapentine plus isoniazid for latent tuberculosis infection: A multicentre randomised controlled trial in Taiwan. Tuberculosis (Edinb). 2018 Jul;111:121-126. doi: 10.1016/j.tube.2018.05.013. Epub 2018 Jun 7.
PubMed 30029896
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Toward a Safe and Reachable Preventive Therapy for LTBI: a Multicenter Randomized Controlled Study in Taiwan
- ClinicalTrials.gov ID
- NCT02208427
- Acronym / sponsor ID
- 201309055MINC
- Conditions
- Latent Tuberculosis Infection
- Keywords
- isoniazid, LTBI, rifapentine, TST
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 283 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 5 Aug 2014 (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.
Background:
Tuberculosis (TB) remains the most important infectious disease in the world. Keys to successful control of TB is rapid diagnosis, prompt treatment, as well as effective preventive therapy for contacts with latent TB infection (LTBI). Current methods for the diagnosis of LTBI are tuberculin skin test (TST) and interferon-gamma release assay (IGRA). For preventive therapy, the recommended regimens include daily isoniazid for 9 months and daily rifampicin for 4 months. By incorporating long-acting rifapentine, a new regimen combining weekly rifapentine and high-dose isoniazid for a total of 12 doses has been proven of equal potency and toxicity. However, the treatment completion rate is much higher in weekly treatment for 3 months than daily treatment for 9 months. It is reasonable that using rifapentine-based preventive therapy can markedly increase the completion rate. However, study is lacking, especially in Asia, the high endemic area of TB.
With the effort of all health care workers and public health personnel, the incidence of TB in Taiwan has gradually declined in recent 10 years. In order to maintain the trend of decreasing in incidence, preventive therapy for LTBI become more and more important. However, which is the best preventive regimen for LTBI is still unknown. Therefore, we conduct the prospective randomized multicenter studies to compare the treatment completion rate of two regimens in Taiwan. The first regimen is daily isoniazid for 9 months. The second is weekly rifapentine plus high-dose isoniazid for 3 months.
Detailed description
Background:
Tuberculosis (TB) remains the most important infectious disease in the world. Keys to successful control of TB is rapid diagnosis, prompt treatment, as well as effective preventive therapy for contacts with latent TB infection (LTBI). Current methods for the diagnosis of LTBI are tuberculin skin test (TST) and interferon-gamma release assay (IGRA). For preventive therapy, the recommended regimens include daily isoniazid for 9 months and daily rifampicin for 4 months. By incorporating long-acting rifapentine, a new regimen combining weekly rifapentine and high-dose isoniazid for a total of 12 doses has been proven of equal potency and toxicity. However, the treatment completion rate is much higher in weekly treatment for 3 months than daily treatment for 9 months. It is reasonable that using rifapentine-based preventive therapy can markedly increase the completion rate. However, study is lacking, especially in Asia, the high endemic area of TB.
With the effort of all health care workers and public health personnel, the incidence of TB in Taiwan has gradually declined in recent 10 years. In order to maintain the trend of decreasing in incidence, preventive therapy for LTBI become more and more important. However, which is the best preventive regimen for LTBI is still unknown. Therefore, we conduct the prospective randomized multicenter studies to compare the treatment completion rate of two regimens in Taiwan. The first regimen is daily isoniazid for 9 months. The second is weekly rifapentine plus high-dose isoniazid for 3 months.
Specific Aims:
- Understanding which of the two preventive regimens has the highest completion rate under supervision.
- Understanding the reasons of interruption in preventive therapy.
- Comparing the side effect profile of the two preventive regimens in Taiwan.
Methods:
In this prospective multicenter study, we will enroll close contacts aged >=12 with positive TST. Chest radiography and sputum studies, if necessary, will be performed to exclude active pulmonary TB. After performing baseline IGRA, participants will be randomized into 2 groups with different preventive regimens. The first regimen is daily isoniazid for 9 months. The second is weekly rifapentine plus high-dose isoniazid for 3 months. The primary outcome is treatment completion rate of the two preventive regimens. The secondary outcome is toxicity. All participant will be followed for 2 years and screen for the development of active pulmonary TB by chest radiography and sputum studies if necessary. The reasons for treatment incompletion will be recorded.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 3M_RH | Experimental | Drug: Rifapentine and Isoniazid for 3 monthsRifapentine and Isoniazid for 3 months: weekly oral rifapentine 15 mg/kg plus isoniazid 15 mg/kg for 12 doses |
| 9M_INH | Active comparator | Drug: Isoniazid for 9 monthsIsoniazid for 9 months: daily oral isoniazid 5 mg/kg for 9 months |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Household contacts of TB or TB contacts in schools or densely-populated institutes
- Age ≥12 year-old
- Index case having smear-positive pulmonary TB
- Contact with index case for >8 hours within single day or >40 hours within total transmissible period
- TST ≥10 mm within one month
Key exclusion criteria (16 listed)
- Clinical or radiographic evidence of active TB
- Index case having culture-negative pulmonary TB
- Index case having Isoniazid or Rifampin-resistant TB
- Receiving medications with significant interactions with Isoniazid, Rifampin, or Rifapentine
- Allergy to Isoniazid, Rifampin, or Rifapentine
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 |
|---|---|---|
| Rifapentine and Isoniazid for 3 monthsAlso: Priftin, Isoniazidweekly oral Rifapentine 15 mg/kg plus Isoniazid 15 mg/kg for 12 doses | Drug | 3M_RH |
| Isoniazid for 9 monthsAlso: Isoniaziddaily oral Isoniazid 5 mg/kg for 9 months under supervision (conventional IPT) | Drug | 9M_INH |
Primary outcome
completion rate
Time frame: 2 years
This prospective randomized interventional study is aimed to assess the completion rate of two different preventive regimens for LTBI by intent-to-treat analysis. Interruption of preventive therapy due to any reasons will be considered as incompletion.
3 secondary outcomes
side effect
Time frame: 3 months in the 3M_RH group and 9 months in the 9M_INH group
interruption
Time frame: 3 months in the 3M_RH group and 9 months in the 9M_INH group
active TB
Time frame: 2 years after enrollment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2016.
- Derived from this study: PubMed 30029896Sun HY, Huang YW, Huang WC, Chang LY, Chan PC, Chuang YC, Ruan SY, Wang JY, Wang JT. Twelve-dose weekly rifapentine plus isoniazid for latent tuberculosis infection: A multicentre randomised controlled trial in Taiwan. Tuberculosis (Edinb). 2018 Jul;111:121-126. doi: 10.1016/j.tube.2018.05.013. Epub 2018 Jun 7.
- Individual participant dataSharing planned: Undecided
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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, MD. PhD. principal investigator
National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rifapentine and Isoniazid for 3 months and Isoniazid for 9 months in people with Latent Tuberculosis Infection, run by National Taiwan University Hospital at 1 site 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 6 inclusion and 16 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 15 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
completion rate (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02208427, which also lists 1 linked publication.
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 15 Dec 2016.