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| Name | Class |
|---|---|
| Thrasher Research Fund | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Isoniazid | Experimental | Isoniazid (INH) ~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. |
|
| No Isoniazid | No Intervention | No INH will be administered to this arm. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Isoniazid | Drug | 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. |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Grace John-Stewart, MD, PhD | University of Washington, Dept of Global Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kisumu County Hospital | Kisumu | Kenya |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17085459 | Background | Zar HJ, Cotton MF, Strauss S, Karpakis J, Hussey G, Schaaf HS, Rabie H, Lombard CJ. Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial. BMJ. 2007 Jan 20;334(7585):136. doi: 10.1136/bmj.39000.486400.55. Epub 2006 Nov 3. | |
| 21732834 | Background |
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| ID | Title | Description |
|---|---|---|
| FG000 | Isoniazid | Isoniazid (INH) ~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. Isoniazid: 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. |
| FG001 | No Isoniazid | No INH will be administered to this arm. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Isoniazid | Isoniazid (INH) ~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. Isoniazid: 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Final analysis 132 in Isoniazid (14 without endpoint and 4 discontinued) and 133 in No Isoniazid arm (9 without primary endpoint, 8 discontinued) | Posted | Number | participants | No | at 12 months post randomization |
|
Adverse event data were collected throughout the study, for two years, two months.
Adverse events include Grade ≥3 severe adverse events by DAIDS scale
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Isoniazid | Isoniazid (INH) ~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. Isoniazid: 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| HIV infection | Infections and infestations | DAIDS 2.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Sylvia M. LaCourse | University of Washington | 206-616-5978 | sylvial2@uw.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 1, 2020 | Nov 12, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 22, 2019 | Nov 12, 2020 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 11, 2017 | Nov 12, 2020 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| ID | Term |
|---|---|
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
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| ID | Term |
|---|---|
| D007538 | Isoniazid |
| ID | Term |
|---|---|
| D006834 | Hydrazines |
| D009930 | Organic Chemicals |
| D007539 | Isonicotinic Acids |
| D000147 | Acids, Heterocyclic |
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|
Number of infants with a combined endpoint of MTB infection, TB disease, and death
|
| 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
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 |
| Madhi SA, Nachman S, Violari A, Kim S, Cotton MF, Bobat R, Jean-Philippe P, McSherry G, Mitchell C; P1041 Study Team. Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children. N Engl J Med. 2011 Jul 7;365(1):21-31. doi: 10.1056/NEJMoa1011214. |
| 35607710 | Result | LaCourse SM, Escudero JN, Mecha J, Warr AJ, Richardson BA, Carimo N, Cranmer LM, Maleche-Obimbo E, Matemo D, Kinuthia J, Hawn TR, John-Stewart G. Cumulative Mycobacterium tuberculosis Infection Incidence (Measured Primarily by Tuberculin Skin Test) Among Infants With Human Immunodeficiency Virus Exposure: Observational Follow-up of an Isoniazid Prophylaxis Trial. Clin Infect Dis. 2022 Dec 19;75(12):2253-2256. doi: 10.1093/cid/ciac393. |
| 32564076 | Derived | LaCourse SM, Richardson BA, Kinuthia J, Warr AJ, Maleche-Obimbo E, Matemo D, Cranmer LM, Mecha J, Escudero JN, Hawn TR, John-Stewart G. A Randomized Controlled Trial of Isoniazid to Prevent Mycobacterium tuberculosis Infection in Kenyan Human Immunodeficiency Virus-Exposed Uninfected Infants. Clin Infect Dis. 2021 Jul 15;73(2):e337-e344. doi: 10.1093/cid/ciaa827. |
| 31969368 | Derived | LaCourse SM, Richardson BA, Kinuthia J, Warr AJ, Maleche-Obimbo E, Matemo D, Cranmer LM, Escudero JN, Hawn TR, John-Stewart GC. Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children. BMJ Open. 2020 Jan 21;10(1):e034308. doi: 10.1136/bmjopen-2019-034308. |
| HIV |
|
| No TB infection endpoint |
|
| No Isoniazid |
No INH will be administered to this arm. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Inter-Quartile Range | weeks |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | No Isoniazid | No INH will be administered to this arm. |
|
|
| Secondary | 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 | Posted | Count of Participants | Participants | Over 12 months after randomization |
|
|
|
| Secondary | Combined Outcome of MTB Infection, TB Disease, and Death | Number of infants with a combined endpoint of MTB infection, TB disease, and death
| Posted | Count of Participants | Participants | Over 12 months after randomization |
|
|
|
| Secondary | 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
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). | Not Posted | Over 12 months after randomization | Participants |
| Primary | 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 | Posted | Number | TB infections/100 person years | at 12 months post randomization |
|
|
|
| 0 |
| 150 |
| 21 |
| 150 |
| 0 |
| 150 |
| EG001 | No Isoniazid | No INH will be administered to this arm. | 1 | 150 | 16 | 150 | 0 | 150 |
| Pneumonia/URTI | Respiratory, thoracic and mediastinal disorders | DAIDS 2.1 | Systematic Assessment |
|
| Gastroenteritis | Gastrointestinal disorders | DAIDS 2.1 | Systematic Assessment |
|
| Malaria | Infections and infestations | DAIDS 2.1 | Systematic Assessment |
|
| Corrective surgery for spina bifida | Surgical and medical procedures | DAIDS 2.1 | Systematic Assessment |
|
| Corrective surgery for cleft palate | Surgical and medical procedures | DAIDS 2.1 | Systematic Assessment |
|
| Corrective surgery for encephalocele | Surgical and medical procedures | DAIDS 2.1 | Systematic Assessment |
|
| Burns | Injury, poisoning and procedural complications | DAIDS 2.1 | Systematic Assessment |
|
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| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D006571 |
| Heterocyclic Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |