Clinical trial NCT02613169: Infant TB Infection Prevention Study
Official title: Preventing Mycobacterium Tuberculosis Infection in HIV-Exposed Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: M. tuberculosis infection
isoniazid
HIV-exposed infants
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Thrasher Research Fund
First posted: 2015-11-24
Enrollment: 300
Sex: ALL
Minimum age (years): 6
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mycobacterium Tuberculosis (MTB) Infection
timeFrame: at 12 months post randomization
measure: Mycobacterium Tuberculosis (MTB) Infection Cumulative Incidence
timeFrame: at 12 months post randomization
Secondary outcomes:
measure: Severe Adverse Events (SAE)
timeFrame: Over 12 months after randomization
measure: Combined Outcome of MTB Infection, TB Disease, and Death
timeFrame: Over 12 months after randomization
measure: Combined Outcome of MTB Infection Including IGRA, TST, and Additional Interferon-gamma-independent Immune Markers in QFT-Plus Supernatants
timeFrame: Over 12 months after randomization
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: Kisumu County Hospital
Study officials:
affiliation: University of Washington, Dept of Global Health
name: Grace John-Stewart, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.