Latent TuberculosisPhase 2/3ASTERoiDNCT03474029
Assessment of the Safety, Tolerability, and Effectiveness of Rifapentine Given Daily for LTBI
A Phase 2/3 study testing Rifapentine daily for 6 weeks, Rifapentine and Isoniazid weekly for 12 weeks and Rifampin and Isoniazid daily for 12 weeks in people with Latent Tuberculosis, run by Centers for Disease Control and Prevention at 21 sites in 8 countries.
Trial summary
This study is conducted to compare the safety and effectiveness of a novel short 6-week regimen of daily rifapentine (6wP, experimental arm) with a comparator arm of 12-16 weeks of rifamycin-based treatment (standard of care, control arm) of latent M. tuberculosis infection (LTBI). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Latent Tuberculosis
- What is being tested?
- Rifapentine daily for 6 weeks, Rifapentine and Isoniazid weekly for 12 weeks and Rifampin and Isoniazid daily for 12 weeks
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,400 participants
- Where
- 21 sitesin 8 countries
- Study dates
- 1 Aug 2019to 31 Dec 2029
- Phase
- Phase 2/3
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Persons with LTBI who do not have evidence of TB disease (see exclusion criteria) and are at increased risk of progression to TB. LTBI or M. tuberculosis infection may be demonstrated by either a positive tuberculin skin test (TST) or a positive interferon gamma release assay (IGRA; e.g., QuantiFERON or T.SPOT.TB). Details of testing definitions and requirements for each risk factor are further described in the MOOP. Persons with LTBI at increased risk of progression to TB are those with at least one of the following:
- Household and other close contacts (> 4 hours of exposure in a one-week period) within 2 years prior to enrollment, of persons with bacteriologically confirmed TB.
- o Acceptable testing approaches for bacteriologic confirmation are 1) culture with rifamycin DST; or, 2) nucleic acid amplification tests (NAATs) that detect M. tuberculosis and detect mutations associated with rifamycin resistance. Additional details on bacteriologic confirmation, including accepted NAATs, will be included in the MOOP.
- Recent M. tuberculosis infection, defined as converting from a documented negative to positive TST or IGRA within 2 years prior to enrollment. Persons without known close contact to someone with active pulmonary TB who have a conversion by IGRA may require additional evaluation to rule out a false conversion. Additional guidance and definitions of conversion are in the MOOP.
- HIV co-infection (with CD4+ T-lymphocyte count > 100 cells/mm3)
- ≥ 2 cm2 of pulmonary parenchymal fibrosis on chest X-ray and no prior history of treatment for TB or LTBI.
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- Recent (within 3 years prior to enrollment) immigration to the United States or other country with low to moderate TB incidence, with abnormal chest X-ray, and no evidence of active TB.
- Recent (within 3 years prior to enrollment) immigration to the United States or other country with low to moderate TB incidence, from a country with an estimated incidence rate of TB > 150 per 100,000 (see Appendix D) and either a positive IGRA or a TST ≥15 mm (TST > 15 mm only applicable for those with recent immigration as their only risk factor for progression to TB).
- Recent (within 3 years prior to enrollment) immigration and seeking refugee/asylum status (see MOOP for additional details) to the United States or other country with low to moderate incidence from a country with an estimated incidence rate of TB > 75 per 100,000 (see Appendix E) and either a positive IGRA or a TST ≥15 mm (TST > 15 mm only applicable for those with recent immigration as their only risk factor for progression to TB).
- Individuals with an increased risk of TB due to medical conditions such as end-stage renal disease.
- Individuals currently using immunosuppressive medications such as chronic steroids.
- Individuals with planned use of TNF-α inhibitors.
- Individuals with planned solid organ or hematologic transplantation
- Willing to provide signed informed consent, or parental permission and participant assent.
- For the following special populations, both inclusion criteria above must be met AND the criteria below depending on stage:
- Pregnant women in their second or third trimester (≥14 weeks gestation).
- Stage 1: Include only those who agree to participate in the semi-intensive PK component.
- Stage 2: Include regardless of semi-intensive PK component participation.
- Children aged less than 12 years
- Stage 1: Include only those who agree to participate in the semi-intensive PK component, based on enrollment strategy presented in Appendix I.
- Stage 2: Include regardless of semi-intensive PK component participation, based on PK findings and enrollment strategy described in Appendix I.
Who cannot join
- Failure to document positive IGRA or TST
- Current breastfeeding.
- Women who are currently pregnant in their first trimester (<14 weeks gestation) or intend to become pregnant within 120 days of enrollment.
- Non-pregnant women of childbearing potential who refuse to practice an adequate method of contraception (barrier method or non-hormonal intrauterine device) or abstain from activities that could lead to pregnancy.
- Current culture-positive TB, clinical TB, or suspected current TB. (Includes cases in which active TB cannot be excluded with reasonable clinical certainty by the site investigator. If sputum samples have been collected AND site investigators have suspicion of active TB, site investigators must wait to review culture results prior to enrollment.)
- TB resistant to any rifamycin in the source case
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- A history of treatment for > 7 consecutive days (if daily dosing) with a rifamycin or >1 week (if weekly dosing) with a rifamycin and INH or > 30 consecutive days with INH within 2 years prior to enrollment.
- A documented history of completing an adequate course of treatment for TB disease or LTBI in a person who is HIV-seronegative.
- History of allergy or intolerance to rifamycins.
- Serum alanine aminotransferase (ALT; SGPT) or serum aspartate aminotransferase (AST; SGOT) > 5x upper limit of normal among persons in whom screening ALT or AST is determined.
- Receiving concomitant medications that are known to be contraindicated with any study drug.
- Weight < 25 kg for participants ≥ 12 years, and weight < 3kg for participants < 12 years
Trial locations and contacts
21 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
21 sites in 8 countries
United States7 sites, 6 recruiting
- Recruiting
Denver Health and Hospital Authority
Denver, Colorado, 80204
Robert Belknap, MD
- Recruiting
New York Harbor Healthcare System
Manhattan, New York, 10001
Benjamin Wu, MD
- Recruiting
New York City Bureau of TB Control
New York, New York, 11201
Joseph Burzynski, MD
- Active, not recruiting
San Antonio VA
San Antonio, Texas, 78201
- Recruiting
Seattle King County Health Department
Seattle, Washington, 98101
Caitlin Reed, MD
- Recruiting
George Washington University
Washington D.C., District of Columbia, 20001
Afsoon Roberts, MD
- Recruiting
Washington DC VA Medical Center
Washington D.C., District of Columbia, 20001
Debra Benator, MD
Canada5 sites, 5 recruiting
- Recruiting
Calgary TB Clinic
Calgary, Alberta, T1Y 6H6
Dina Fisher, MD
- Recruiting
Edmonton TB Clinic
Edmonton, Alberta
Richard Long, MD
- Recruiting
McGill University Health Centre
Montreal, Quebec, H3A 0G4
Dick Menzies, MD
- Recruiting
Toronto Western Hospital
Toronto, Ontario, M5P 1N5
Sarah Brode, MD
- Recruiting
British Columbia Centre for Disease Control
Vancouver, British Columbia
James Johnston, MD
Australia3 sites, 3 recruiting
- Recruiting
Liverpool Hospital
Sydney
Zinta Harrington, MD
- Recruiting
Paramatta Chest
Sydney
Jin-Gun Cho, MD
- Recruiting
Royal Prince Alfred Hospital
Sydney
Greg Fox, MD
Vietnam2 sites, 2 recruiting
- Recruiting
Ho Chin Minh City-District 6 TB Unit
Ho Chi Minh City
Greg Fox, MD
- Recruiting
Ho Chin Minh City-Phoi Viet Resportory Centre
Ho Chi Minh City
Greg Fox, MD
Benin1 site
- Active, not recruiting
National Referral University Hospital for Pneumo-physiology
Cotonou
Haiti1 site, 1 recruiting
- Recruiting
Les Centres Gheskio (INLR) CRS
Port-au-Prince
Jean Pape, MD
South Africa1 site, 1 recruiting
- Not yet recruiting
Desmond Tutu TB Center
Stellenbosch
Anneke Hesseling, MD
Uganda1 site, 1 recruiting
- Recruiting
Joint Clinical Research Centre/ Makerere Univ Med Sch
Kampala
Harriet Mayanja, MD
About this study
Official title: Six Weeks of Daily Rifapentine vs. a Comparator Arm of 12-16 Week Rifamycin-based Treatment of Latent M. Tuberculosis Infection: Assessment of Safety, Tolerability and Effectiveness
This study is conducted to compare the safety and effectiveness of a novel short 6-week regimen of daily rifapentine (6wP, experimental arm) with a comparator arm of 12-16 weeks of rifamycin-based treatment (standard of care, control arm) of latent M. tuberculosis infection (LTBI).
This trial is conducted among persons who are at increased risk of progression to tuberculosis (TB) and require treatment of LTBI. The study will be conducted in low, medium and high TB incidence settings that have treatment of LTBI as their standard of care and offer 12-16 week rifamycin-based therapy as standard of care.
Read more
The hypothesis of this study is that the safety and effectiveness of the experimental treatment (6wP arm) is non-inferior to a comparator arm of 12-16 weeks of rifamycin-based treatment of LTBI (control arm).
Participants are enrolled and randomly assigned to one of the two study arms: experimental 6wP or control. The comparator (control) arm's treatment regimens include 12 weeks of once-weekly isoniazid (INH) and rifapentine (3HP), 12 weeks of daily INH and rifampin (3HR), and 16 weeks of daily rifampin (4R). A total of 560 participants per arm (1,120 total) for the evaluation of safety and 1,700 participants per arm (3,400 total) for the evaluation of effectiveness will be enrolled, given treatment as per randomization assignment, and followed for 24 months from the date of enrollment.
After completion of data collection, statistical analyses will be conducted to compare proportions of drug discontinuation due to adverse drug reaction (ADR) and proportions of newly diagnosed tuberculosis between 6wP and control arm.
- Conditions
- Latent Tuberculosis
- Being tested
- Rifapentine daily for 6 weeks, Rifapentine and Isoniazid weekly for 12 weeks, Rifampin and Isoniazid daily for 12 weeks, Rifampin daily for 16 weeks
- Keywords
- latent tuberculosis, rifapentine
- 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 daily for 6 weeksDrug
Also called priftin
600 mg of Rifapentine (RPT) given once daily (o.d., omni die) for 6 weeks (6wP).
Rifapentine and Isoniazid weekly for 12 weeksDrug
Rifapentine (RPT) 900 mg and isoniazid (INH) 900 mg given once-weekly for 12 weeks (3HP).*
*Dose adjustments based on patient's weight will be made according to ATS/CDC/IDSA guidelines.
RPT 900 mg once-weekly for persons weighing > 50 kg. For persons weighing < 50 kg, the following doses will be given: weight > 25-32 kg - RPT 600 mg; weight > 32-50 kg - RPT 750 mg; + INH 15 mg/kg (round up to nearest 50 or 100 mg; 900 mg max).
Rifampin and Isoniazid daily for 12 weeksDrug
Rifampin (RIF) 600 mg and Isoniazid (INH) 300 mg given once-daily for 12 weeks (3HR)*.
*Dose adjustments based on patient's weight will be made according to ATS/CDC/IDSA guidelines.
RIF 600 mg daily for persons weighing > 50 kg. For persons weighing < 50 kg, give 10 mg/kg daily; round up to nearest 50 or 100 mg; + INH 5 mg/kg daily (rounded up to nearest 50 or 100 mg; 300 mg max).
Rifampin daily for 16 weeksDrug
Rifampin (RIF) 600 mg given once-daily for 16 weeks (4R).*
*Dose adjustments based on patient's weight will be made according to ATS/CDC/IDSA guidelines.
RIF 600 mg daily for persons weighing > 50 kg. For persons weighing < 50 kg, 10 mg/kg daily; round up to nearest 50 or 100 mg.
| Study group | Role | What they receive |
|---|---|---|
| 6 weeks of daily rifapentine (6wP) | Experimental | Rifapentine daily for 6 weeks: 600 mg of Rifapentine (RPT) given once daily for 6 weeks Receives: Drug: Rifapentine daily for 6 weeks |
| 12-16 week rifamycin-based regimen | Active comparator | A 12-16 week rifamycin-based regimen available at the participant's site:
"Rifapentine and Isoniazid weekly for 12 weeks" (3HP) or "Rifampin and Isoniazid daily for 12 weeks" (3HR) or "Rifampin daily for 16 weeks" (4R) Receives: Drug: Rifapentine and Isoniazid weekly for 12 weeks; Drug: Rifampin and Isoniazid daily for 12 weeks; Drug: Rifampin daily for 16 weeks |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment discontinuation due to adverse drug reaction
- Safety: Drug discontinuation due to adverse drug reaction (ADR) associated with 6wP and the rifamycin-based comparator arm (3HP, 3HR, or 4R).
- Attribution of an adverse event (AE) to study drugs will be initially determined by the local site investigator, reviewed by an independent, blinded adjudication panel and with final attribution determined by the sponsor.
Measured: from the date of enrollment to the date of scheduled completion of assigned treatment
Culture-confirmed tuberculosis (TB) in participants 18 years old and older and culture-confirmed or clinical TB in participants less then 18 years old.
- Effectiveness: Culture-confirmed TB in participants > 18 years old and culture-confirmed or clinical TB in participants < 18 years old.
- Diagnosis of culture-confirmed TB will be performed using liquid and/or solid media.
- An independent, blinded adjudication panel will review all TB events.
Measured: within 24 months from the date of enrollment
Secondary outcomes (17)
Proportion who complete assigned treatment
Proportion of participants who complete assigned study treatment during the study period. Treatment completion is defined as taking at least 90% of the prescribed doses within the protocol-defined time period.
Measured: from date of enrollment until the maximum accepted time for treatment completion as follows: 9 weeks for 6wP treatment, 16 weeks for 3HP, 16 weeks for 3HP, and 21 weeks for 4R
Proportion of Participants Who Complete Assigned Study Treatment
Proportion of participants who complete assigned study treatment during the study period. Treatment completion is defined as taking at least 90% of the prescribed doses within the protocol-defined time period.
Measured: from date of enrollment until the maximum accepted time for treatment completion as follows: 9 weeks for 6wP treatment, 16 weeks for 3HP, 16 weeks for 3HP, and 21 weeks for 4R
Proportion with any grade 3, 4, or 5 (i.e., death) adverse event associated with study drug
Proportion of participants who experience at least one Grade 3, 4, or 5 adverse event related to study drug during the study period. Adverse events will be graded using the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 (Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death). Relationship to study drug will be determined by the site investigator and reviewed by an independent blinded adjudication panel.
Measured: within 6 months from the date of enrollment
Proportion of Participants Who Die From Any Cause
Proportion of participants who die from any cause during the study period. Deaths will be ascertained through participant follow-up, medical records, or death registries and reviewed by an independent blinded adjudication panel.
Measured: within 24 months from the date of enrollment
Proportion of Participants With Hepatotoxicity or Non-Hepatotoxic Systemic Drug Reactions
Proportion of participants who experience at least one event of hepatotoxicity or non-hepatotoxic systemic drug reaction during the study period. Hepatotoxicity and systemic drug reactions will be defined per protocol and graded using Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Relationship to study drug will be determined by the investigator.
Measured: within 6 months from the date of enrollment
Proportion of Participants with Culture-Confirmed or Clinical Tuberculosis (TB)
Proportion of participants who develop culture-confirmed or clinical tuberculosis (TB) during the study period, regardless of age. Culture-confirmed TB will be based on microbiological confirmation using liquid and/or solid culture methods. Clinical TB will be defined according to protocol-specified diagnostic criteria and adjudicated by an independent blinded panel.
Measured: within 24 months from the date of enrollment
Proportion of Participants Who Develop Tuberculosis (TB) Among Those Who Complete Assigned Study Treatment
Proportion of participants who develop tuberculosis (TB) among those who complete assigned study treatment during the study period. Completion of treatment is defined per protocol. TB will be defined as culture-confirmed or clinical TB based on microbiological or protocol-specified clinical criteria and reviewed by an independent blinded adjudication panel.
Measured: within 24 months from the date of enrollment
Proportion of Participants With HIV Infection Who Discontinue Study Treatment Due to Adverse Drug Reactions
Proportion of HIV-infected patients with drug discontinuation due to adverse drug reaction (ADR) associated with experimental treatment (6wP) or active comparator treatment (the rifamycin-based 3HP, 3HR, or 4R) . Attribution of an adverse event (AE) to study drugs will be determined by the local site investigator.
Measured: from date of enrollment until the maximum accepted time for treatment completion as follows: 9 weeks for 6wP treatment, 16 weeks for 3HP, 16 weeks for 3HP, and 21 weeks for 4R
Safety (defined as treatment discontinuation due to adverse drug reaction) among participants < 18 years old.
Proportion of participants < 18 years old with drug discontinuation due to adverse drug reaction (ADR) associated with experimental treatment (6wP) or active comparator treatment (the rifamycin-based 3HP, 3HR, or 4R) . Attribution of an adverse event (AE) to study drugs will be determined by the local site investigator.
Measured: from date of enrollment until the maximum accepted time for treatment completion as follows: 9 weeks for 6wP treatment, 16 weeks for 3HP, 16 weeks for 3HP, and 21 weeks for 4R
Tolerability (defined as proportion of with drug discontinuation for any reason) among participants with human immunodeficiency virus (HIV) infection.
Proportion of HIV-infected patients with drug discontinuation for any reason
Measured: from date of enrollment until the maximum accepted time for treatment completion as follows: 9 weeks for 6wP treatment, 16 weeks for 3HP, 16 weeks for 3HP, and 21 weeks for 4R
Tolerability (defined as proportion of with drug discontinuation for any reason) among participants < 18 years old.
Proportion of participants < 18 years old with drug discontinuation for any reason
Measured: from date of enrollment until the maximum accepted time for treatment completion as follows: 9 weeks for 6wP treatment, 16 weeks for 3HP, 16 weeks for 3HP, and 21 weeks for 4R
Effectiveness among participants with human immunodeficiency virus (HIV) infection.
Proportion of HIV-infected patients with culture-confirmed tuberculosis (TB) in participants 18 years old and older and culture-confirmed or clinical TB in participants less then 18 years old. Diagnosis of culture-confirmed TB will be performed using liquid and/or solid media methods.
Measured: within 24 months from the date of enrollment
Effectiveness among participants < 18 years old.
Proportion of participants < 18 years old with culture-confirmed tuberculosis or clinical TB. Diagnosis of culture-confirmed TB will be performed using liquid and/or solid media methods.
Measured: within 24 months from the date of enrollment
Proportion with any grade 3, 4, or 5 (i.e., death) adverse event during the time period of 6 months after enrollment
Proportion of participants who experience at least one Grade 3, 4, or 5 adverse event within 6 months after enrollment. Adverse events will be graded using the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 (Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death).
Measured: within 6 months from the date of enrollment
Effectiveness among pregnant participants
Proportion of pregnant participants with culture-confirmed tuberculosis or clinical TB. Diagnosis of culture-confirmed TB will be performed using liquid and/or solid media methods.
Measured: within 24 months from the date of enrollment
Safety (defined as treatment discontinuation due to adverse drug reaction) among pregnant participants.
Proportion of pregnant participants with drug discontinuation due to adverse drug reaction (ADR) associated with experimental treatment (6wP) or active comparator treatment (the rifamycin-based 3HP, 3HR, or 4R) .
Measured: from date of enrollment until the maximum accepted time for treatment completion as follows: 9 weeks for 6wP treatment, 16 weeks for 3HP, 16 weeks for 3HP, and 21 weeks for 4R
Tolerability (defined as proportion of with drug discontinuation for any reason) among pregnant participants
Proportion of pregnant participants with drug discontinuation for any reason
Measured: from date of enrollment until the maximum accepted time for treatment completion as follows: 9 weeks for 6wP treatment, 16 weeks for 3HP, 16 weeks for 3HP, and 21 weeks for 4R
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2018
- Study start1 Aug 2019
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Latent TuberculosisStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3,400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centers for Disease Control and Prevention
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Timothy Sterling, MD, Study chair, Vanderbilt University Medical CenterRobert Belknap, MD, Study chair, Denver Public Health (USA)Amber Robinson, PhD, Study director, Centers for Disease Control and PreventionRosanna M Boyd, PhD, Study director, Centers for Disease Control (USA)Dick Menzies, MD, Study chair, McGill University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03474029
- Sponsor's protocol ID
- CDC-NCHSTP-7024
- Acronym
- ASTERoiD
- Status last verified
- May 2026
- First submitted
- 8 Mar 2018
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided