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Trial record 2 of 2 for:    Study 32 AND TBTC

Assessment of the Safety, Tolerability, and Effectiveness of Rifapentine Given Daily for LTBI (ASTERoiD)

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ClinicalTrials.gov Identifier: NCT03474029
Recruitment Status : Recruiting
First Posted : March 22, 2018
Last Update Posted : August 7, 2019
Sponsor:
Collaborator:
British Medical Research Council
Information provided by (Responsible Party):
Centers for Disease Control and Prevention

Brief 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).

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 the United States, the United Kingdom, and other countries with low to moderate TB incidence (< 100 TB cases per 100,000 population) that have treatment of LTBI as their standard of care and offer 12-16 week rifamycin-based therapy as standard of care.

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.


Condition or disease Intervention/treatment Phase
Latent Tuberculosis Drug: Rifapentine daily for 6 weeks Drug: Rifapentine and Isoniazid weekly for 12 weeks Drug: Rifampin and Isoniazid daily for 12 weeks Drug: Rifampin daily for 16 weeks Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 1, 2019
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis
Drug Information available for: Rifapentine

Arm Intervention/treatment
Experimental: 6 weeks of daily rifapentine (6wP)
Rifapentine daily for 6 weeks: 600 mg of Rifapentine (RPT) given once daily for 6 weeks
Drug: Rifapentine daily for 6 weeks
600 mg of Rifapentine (RPT) given once daily (o.d., omni die) for 6 weeks (6wP).
Other Name: priftin

Active Comparator: 12-16 week rifamycin-based regimen

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)

Drug: Rifapentine and Isoniazid weekly for 12 weeks

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).


Drug: Rifampin and Isoniazid daily for 12 weeks

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).


Drug: Rifampin daily for 16 weeks

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.





Primary Outcome Measures :
  1. Treatment discontinuation due to adverse drug reaction [ Time Frame: from the date of enrollment to the date of scheduled completion of assigned treatment ]
    Safety outcome. 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.

  2. Culture-confirmed tuberculosis (TB) in participants 18 years old and older and culture-confirmed or clinical TB in participants less then 18 years old. [ Time Frame: within 24 months from the date of enrollment ]
    Effectiveness outcome. 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.


Secondary Outcome Measures :
  1. Proportion who complete assigned treatment [ Time Frame: 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 ]
  2. Proportion with drug discontinuation for any reason [ Time Frame: 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 ]
  3. Proportion with any grade 3, 4, or 5 (i.e., death) adverse event associated with study drug [ Time Frame: from date of enrollment to the date of treatment completion plus 14 days: up to 11 weeks for 6wP treatment, up to 18 weeks for 3HP, up to 18 weeks for 3HP, and up to 23 weeks for 4R. ]
  4. Proportion who have died for any reason [ Time Frame: within 24 months from the date of enrollment ]
  5. Proportion with hepatitis and non-hepatotoxic systemic drug reactions [ Time Frame: from date of enrollment to the date of treatment completion plus 14 days: up to 11 weeks for 6wP treatment, up to 18 weeks for 3HP, up to 18 weeks for 3HP, and up to 23 weeks for 4R. ]
  6. Proportion with culture-confirmed or clinical TB regardless of age [ Time Frame: within 24 months from the date of enrollment ]
  7. Proportion with TB among those who complete assigned therapy [ Time Frame: within 24 months from the date of enrollment ]
  8. Safety (defined as treatment discontinuation due to adverse drug reaction) among participants with human immunodeficiency virus (HIV) infection. [ Time Frame: 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 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.

  9. Safety (defined as treatment discontinuation due to adverse drug reaction) among participants < 18 years old. [ Time Frame: 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 < 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.

  10. Tolerability (defined as proportion of with drug discontinuation for any reason) among participants with human immunodeficiency virus (HIV) infection. [ Time Frame: 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 HIV-infected patients with drug discontinuation for any reason

  11. Tolerability (defined as proportion of with drug discontinuation for any reason) among participants < 18 years old. [ Time Frame: 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 < 18 years old with drug discontinuation for any reason

  12. Effectiveness among participants with human immunodeficiency virus (HIV) infection. [ Time Frame: within 24 months from the date of enrollment ]
    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.

  13. Effectiveness among participants < 18 years old. [ Time Frame: within 24 months from the date of enrollment ]
    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.


Other Outcome Measures:
  1. Proportions of drug discontinuation due to adverse drug reactions in experimental (6wP) arm and each treatment regimen in the comparator arm: 3HP, 3HR, 4R [ Time Frame: 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 ]
  2. Proportions of treatment discontinuations for any reason in experimental (6wP) arm and each treatment regimen in the comparator arm: 3HP, 3HR, 4R [ Time Frame: 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 ]
  3. Effectiveness of experimental (6wP) arm and each treatment regimen in the comparator arm: 3HP, 3HR, 4R [ Time Frame: within 24 months from the date of enrollment ]
    Proportion of participants 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.

  4. Proportion of treatment completion with an alternative regimen after discontinuation of study therapy [ Time Frame: from the date of enrollment to the date of scheduled completion of assigned treatment (up to 24 month) ]
  5. Proportion with resistance to rifamycins or isoniazid among persons who develop TB to each regimen in the comparator arm: 3HP, 3HR, 4R. [ Time Frame: within 24 months from the date of enrollment ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or non-pregnant, non-breastfeeding females > 12 years old. Women of child-bearing potential who are not surgically sterilized must agree to practice an adequate method of contraception (barrier method or non-hormonal intrauterine device) or abstain from heterosexual intercourse during study drug treatment.
  • Persons with LTBI who do not have evidence of TB disease and are at increased risk of progression to TB. 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). Persons with LTBI at increased risk of progression to TB are those with one of the following:

    1. Household and other close contacts (> 4 hours of exposure in a one week period) within 2 years prior to enrollment, of persons with culture-confirmed TB A positive nucleic acid amplification test (NAAT)/GeneXpert in the source case may be used for enrollment prior to culture confirmation
    2. 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.
    3. HIV co-infection.
    4. ≥ 2 cm2 of pulmonary parenchymal fibrosis on chest X-ray and no prior history of treatment for TB or LTBI.
    5. Recent (within 2 years prior to enrollment) immigration to the United States, United Kingdom, or other country with low to moderate TB incidence, with abnormal chest X-ray, and no evidence of active TB.
    6. Recent (within 2 years prior to enrollment) immigration to the United States, United Kingdom, 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).
    7. An increased risk of TB due to medical conditions such as end-stage renal disease, or due to use of immunosuppressive medications such as chronic steroids or TNF-alpha inhibitors.
  • HIV-infected persons who are close contacts of a TB case, regardless of TST or IGRA result.
  • Willing to provide signed informed consent, or parental permission and participant assent.

Exclusion Criteria:

  • Current confirmed culture-positive or clinical TB.
  • Suspected current TB. Includes cases in which active TB cannot be eliminated as a possibility (by the site investigator)
  • TB resistant to any rifamycin in the source case
  • A history of treatment for > 7 consecutive days with a rifamycin 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 baseline ALT or AST is determined+.
  • HIV-seropositive and on antiretroviral therapy that cannot be given with rifampin or rifapentine due to drug-drug interactions.
  • Receiving concomitant medications that are known to be contraindicated with any study drug.
  • Females who are currently pregnant, breastfeeding, or intend to become pregnant within 120 days of enrollment.
  • Weight < 25 kg.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03474029


Contacts
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Contact: Rosanna M Boyd, PhD +1 (404)-553-7434 icg7@cdc.gov
Contact: TBTC Research Administrator +1 (800)-232-4636 tbtcresearchadmin@cdc.gov

Locations
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United States, California
California Department of Public Health Not yet recruiting
San Francisco, California, United States, 94102
Contact: Payam Nahid, MD         
United States, Colorado
Denver Health and Hospital Authority Recruiting
Denver, Colorado, United States, 80204
Contact: Robert Belknap, MD         
United States, New York
Columbia University Not yet recruiting
New York, New York, United States, 10027
Contact: Neil Schlugger, MD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37235
Contact: Timothy Sterling, MD         
United States, Texas
Austin TB Clinic Recruiting
Austin, Texas, United States, 78702
Contact: Marc Weiner, MD         
University of North Texas Health Science Center Not yet recruiting
Fort Worth, Texas, United States, 76107
Contact: Thad Miller, PhD         
University of Texas Health Science Center Recruiting
San Antonio, Texas, United States, 78229
Contact: Marc Weiner, MD       weiner@uthscsa.edu   
Sponsors and Collaborators
Centers for Disease Control and Prevention
British Medical Research Council
Investigators
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Study Chair: Timothy Sterling, MD Vanderbilt University Medical Center (USA)
Study Chair: Robert Belknap, MD Denver Public Health (USA)
Study Chair: Ibrahim Abubakar, MD University College London, UK.
Study Director: Rosanna M Boyd, PhD Centers for Disease Control (USA)

Additional Information:
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Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT03474029     History of Changes
Other Study ID Numbers: CDC-NCHSTP-7024
First Posted: March 22, 2018    Key Record Dates
Last Update Posted: August 7, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centers for Disease Control and Prevention:
latent tuberculosis
rifapentine
Additional relevant MeSH terms:
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Tuberculosis
Latent Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Rifampin
Rifapentine
Isoniazid
Rifamycins
Rifamycin SV
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents
Antirheumatic Agents