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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03474029




Registration number
NCT03474029
Ethics application status
Date submitted
8/03/2018
Date registered
22/03/2018
Date last updated
26/09/2024

Titles & IDs
Public title
Assessment of the Safety, Tolerability, and Effectiveness of Rifapentine Given Daily for LTBI
Scientific 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
Secondary ID [1] 0 0
CDC-NCHSTP-7024
Universal Trial Number (UTN)
Trial acronym
ASTERoiD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Latent Tuberculosis 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rifapentine daily for 6 weeks
Treatment: Drugs - Rifapentine and Isoniazid weekly for 12 weeks
Treatment: Drugs - Rifampin and Isoniazid daily for 12 weeks
Treatment: Drugs - Rifampin daily for 16 weeks

Experimental: 6 weeks of daily rifapentine (6wP) - Rifapentine daily for 6 weeks: 600 mg of Rifapentine (RPT) given once daily for 6 weeks

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)


Treatment: Drugs: Rifapentine daily for 6 weeks
600 mg of Rifapentine (RPT) given once daily (o.d., omni die) for 6 weeks (6wP).

Treatment: Drugs: 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).

Treatment: Drugs: 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).

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Treatment discontinuation due to adverse drug reaction
Timepoint [1] 0 0
from the date of enrollment to the date of scheduled completion of assigned treatment
Primary outcome [2] 0 0
Culture-confirmed tuberculosis (TB) in participants 18 years old and older and culture-confirmed or clinical TB in participants less then 18 years old.
Timepoint [2] 0 0
within 24 months from the date of enrollment
Secondary outcome [1] 0 0
Proportion who complete assigned treatment
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Proportion with drug discontinuation for any reason
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Proportion with any grade 3, 4, or 5 (i.e., death) adverse event associated with study drug
Timepoint [3] 0 0
within 6 months from the date of enrollment
Secondary outcome [4] 0 0
Proportion who have died for any reason
Timepoint [4] 0 0
within 24 months from the date of enrollment
Secondary outcome [5] 0 0
Proportion with hepatitis and non-hepatotoxic systemic drug reactions
Timepoint [5] 0 0
within 6 months from the date of enrollment
Secondary outcome [6] 0 0
Proportion with culture-confirmed or clinical TB regardless of age
Timepoint [6] 0 0
within 24 months from the date of enrollment
Secondary outcome [7] 0 0
Proportion with TB among those who complete assigned therapy
Timepoint [7] 0 0
within 24 months from the date of enrollment
Secondary outcome [8] 0 0
Safety (defined as treatment discontinuation due to adverse drug reaction) among participants with human immunodeficiency virus (HIV) infection.
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
Safety (defined as treatment discontinuation due to adverse drug reaction) among participants < 18 years old.
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
Tolerability (defined as proportion of with drug discontinuation for any reason) among participants with human immunodeficiency virus (HIV) infection.
Timepoint [10] 0 0
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
Secondary outcome [11] 0 0
Tolerability (defined as proportion of with drug discontinuation for any reason) among participants < 18 years old.
Timepoint [11] 0 0
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
Secondary outcome [12] 0 0
Effectiveness among participants with human immunodeficiency virus (HIV) infection.
Timepoint [12] 0 0
within 24 months from the date of enrollment
Secondary outcome [13] 0 0
Effectiveness among participants < 18 years old.
Timepoint [13] 0 0
within 24 months from the date of enrollment

Eligibility
Key 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 (with CD4+ T-lymphocyte count > 100 cells/mm3).
4. = 2 cm2 of pulmonary parenchymal fibrosis on chest X-ray and no prior history of treatment for TB or LTBI.
5. 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.
6. Recent (within 2 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
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.
* Willing to provide signed informed consent, or parental permission and participant assent.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2029
Actual
Sample size
Target
3400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Liverpool Hospital - Sydney
Recruitment hospital [2] 0 0
Paramatta Chest - Sydney
Recruitment hospital [3] 0 0
Royal Prince Alfred Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
United States of America
State/province [5] 0 0
Washington
Country [6] 0 0
Canada
State/province [6] 0 0
Alberta
Country [7] 0 0
Canada
State/province [7] 0 0
British Columbia
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
South Africa
State/province [10] 0 0
Stellenbosch

Funding & Sponsors
Primary sponsor type
Government body
Name
Centers for Disease Control and Prevention
Address
Country

Ethics approval
Ethics application status

Summary
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 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.

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.
Trial website
https://clinicaltrials.gov/study/NCT03474029
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Timothy Sterling, MD
Address 0 0
Vanderbilt University Medical Center, USA
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Rosanna M Boyd, PhD
Address 0 0
Country 0 0
Phone 0 0
+1 (404)-553-7434
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03474029