Infant TB Infection Prevention Study

Study Overview
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Brief Summary
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Randomized controlled trial (RCT) of isoniazid (INH) vs. no INH to prevent Mycobacterium tuberculosis infection in HIV-exposed uninfected (HEU) infants.

Detailed Description
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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.

Official Title
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Preventing Mycobacterium Tuberculosis Infection in HIV-Exposed Infants

Conditions
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Tuberculosis

Intervention / Treatment
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* Drug: Isoniazid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV exposed infants Aged 6 weeks within (+ 4 weeks) Born to HIV-infected mothers Not premature and over 2.5 kg Exclusion Criteria: Infants with known exposure to active TB in household Premature and < 2.5 kg

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 10 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Isoniazid<br>Isoniazid (INH)  10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. | Drug: Isoniazid<br>* 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.<br>* Other names: INH;|
| No Intervention: No Isoniazid<br>No INH will be administered to this arm. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | at 12 months post randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 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). | Over 12 months after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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M. tuberculosis infection, isoniazid, HIV-exposed infants