Randomized controlled trial (RCT) of isoniazid (INH) vs. no INH to prevent Mycobacterium tuberculosis infection in HIV-exposed uninfected (HEU) infants.
The purpose of this trial is to determine whether isoniazid (INH) reduces the risk of Mycobacterium tuberculosis (MTB) infection in HIV-exposed but uninfected (HEU) children, as well as to determine epidemiologic and immunologic correlates of MTB infection in HEU.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
300
HIV-exposed uninfected infants will be randomized to receive either INH or no INH daily for 12 months for the prevention of Mycobacterium tuberculosis (MTB) infection.
Kisumu County Hospital
Kisumu, Kenya
Mycobacterium Tuberculosis (MTB) Infection
Among HEU infants enrolled at approximately 6 weeks of age, compare the risk of acquiring MTB infection during 1 year of follow-up in infants randomized to receive INH vs. no INH using an interferon-gamma release (IGRA) QuantiFERON-TB Gold Plus (QFT-Plus) assay or tuberculin skin test as part of a composite endpoint to determine MTB infection status
Time frame: at 12 months post randomization
Mycobacterium Tuberculosis (MTB) Infection Cumulative Incidence
Among HEU infants enrolled at approximately 6 weeks of age, compare the risk of acquiring MTB infection during 1 year of follow-up in infants randomized to receive INH vs. no INH using an interferon-gamma release (IGRA) QuantiFERON-TB Gold Plus (QFT-Plus) assay or tuberculin skin test as part of a composite endpoint to determine MTB infection status
Time frame: at 12 months post randomization
Severe Adverse Events (SAE)
Number of infants with grade 3 or higher treatment-related adverse events as assessed by DAIDS Table for the Grading Severity of Pediatric Adverse Experiences
Time frame: Over 12 months after randomization
Combined Outcome of MTB Infection, TB Disease, and Death
Number of infants with a combined endpoint of MTB infection, TB disease, and death * MTB infection as measured by IGRA or tuberculin skin test at 12 months post-enrollment * TB disease including microbiologically confirmed (culture or Xpert positive), or probable TB (clinical diagnosis). * Death of infant
Time frame: Over 12 months after randomization
Combined Outcome of MTB Infection Including IGRA, TST, and Additional Interferon-gamma-independent Immune Markers in QFT-Plus Supernatants
Number of infants with MTB infection as measured by * IGRA, or * Tuberculin skin test (\>10 mm) at 12 months post-enrollment, or * Interferon-gamma-independent immune markers in QFT-Plus supernatants Combined outcome will be defined as positive if IGRA OR TST OR interferon-gamma-independent marker is positive and combined outcome will be defined as negative if none of these is positive (if children do not have all three markers the definition will hold for available markers).
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Time frame: Over 12 months after randomization