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Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children

INTRODUCTION: HIV-exposed uninfected (HEU) infants in tuberculosis (TB) endemic settings are at high risk of Mycobacterium tuberculosis (Mtb) infection and TB disease, even in the absence of known Mtb exposure. Because infancy is a time of rapid progression from primary infection to active TB diseas...

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Autores principales: LaCourse, Sylvia M, Richardson, Barbra A, Kinuthia, John, Warr, A J, Maleche-Obimbo, Elizabeth, Matemo, Daniel, Cranmer, Lisa M, Escudero, Jaclyn N, Hawn, Thomas R, John-Stewart, Grace C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045242/
https://www.ncbi.nlm.nih.gov/pubmed/31969368
http://dx.doi.org/10.1136/bmjopen-2019-034308
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author LaCourse, Sylvia M
Richardson, Barbra A
Kinuthia, John
Warr, A J
Maleche-Obimbo, Elizabeth
Matemo, Daniel
Cranmer, Lisa M
Escudero, Jaclyn N
Hawn, Thomas R
John-Stewart, Grace C
author_facet LaCourse, Sylvia M
Richardson, Barbra A
Kinuthia, John
Warr, A J
Maleche-Obimbo, Elizabeth
Matemo, Daniel
Cranmer, Lisa M
Escudero, Jaclyn N
Hawn, Thomas R
John-Stewart, Grace C
author_sort LaCourse, Sylvia M
collection PubMed
description INTRODUCTION: HIV-exposed uninfected (HEU) infants in tuberculosis (TB) endemic settings are at high risk of Mycobacterium tuberculosis (Mtb) infection and TB disease, even in the absence of known Mtb exposure. Because infancy is a time of rapid progression from primary infection to active TB disease, it is important to define when and how TB preventive interventions exert their effect in order to develop effective prevention strategies in this high-risk population. METHODS AND ANALYSIS: We designed a non-blinded randomised controlled trial to determine efficacy of isoniazid (INH) to prevent primary Mtb infection among HEU children. Target sample size is 300 (150 infants in each arm). Children are enrolled at 6 weeks of age from maternal and child health clinics in Kenya and are randomised to receive 12 months of daily INH ~10 mg/kg plus pyridoxine or no INH. The primary endpoint is Mtb infection, assessed by interferon-gamma release assay QuantiFERON-TB Gold Plus (QFT-Plus) or tuberculin skin test after 12 months post-enrolment. Secondary outcomes include severe adverse events, expanded Mtb infection definition using additional QFT-Plus supernatant markers and determining correlates of Mtb infection. Exploratory analyses include a combined outcome of TB infection, disease and mortality, and sensitivity analyses excluding infants with baseline TB-specific responses on flow cytometry. ETHICS AND DISSEMINATION: An external and independent Data and Safety Monitoring Board monitors adverse events. Results will be disseminated through peer-reviewed journals, presentations at local and international conferences to national and global policy-makers, the local community and participants. TRIAL REGISTRATION NUMBER: NCT02613169; Pre-results.
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spelling pubmed-70452422020-03-09 Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children LaCourse, Sylvia M Richardson, Barbra A Kinuthia, John Warr, A J Maleche-Obimbo, Elizabeth Matemo, Daniel Cranmer, Lisa M Escudero, Jaclyn N Hawn, Thomas R John-Stewart, Grace C BMJ Open Infectious Diseases INTRODUCTION: HIV-exposed uninfected (HEU) infants in tuberculosis (TB) endemic settings are at high risk of Mycobacterium tuberculosis (Mtb) infection and TB disease, even in the absence of known Mtb exposure. Because infancy is a time of rapid progression from primary infection to active TB disease, it is important to define when and how TB preventive interventions exert their effect in order to develop effective prevention strategies in this high-risk population. METHODS AND ANALYSIS: We designed a non-blinded randomised controlled trial to determine efficacy of isoniazid (INH) to prevent primary Mtb infection among HEU children. Target sample size is 300 (150 infants in each arm). Children are enrolled at 6 weeks of age from maternal and child health clinics in Kenya and are randomised to receive 12 months of daily INH ~10 mg/kg plus pyridoxine or no INH. The primary endpoint is Mtb infection, assessed by interferon-gamma release assay QuantiFERON-TB Gold Plus (QFT-Plus) or tuberculin skin test after 12 months post-enrolment. Secondary outcomes include severe adverse events, expanded Mtb infection definition using additional QFT-Plus supernatant markers and determining correlates of Mtb infection. Exploratory analyses include a combined outcome of TB infection, disease and mortality, and sensitivity analyses excluding infants with baseline TB-specific responses on flow cytometry. ETHICS AND DISSEMINATION: An external and independent Data and Safety Monitoring Board monitors adverse events. Results will be disseminated through peer-reviewed journals, presentations at local and international conferences to national and global policy-makers, the local community and participants. TRIAL REGISTRATION NUMBER: NCT02613169; Pre-results. BMJ Publishing Group 2020-01-21 /pmc/articles/PMC7045242/ /pubmed/31969368 http://dx.doi.org/10.1136/bmjopen-2019-034308 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Infectious Diseases
LaCourse, Sylvia M
Richardson, Barbra A
Kinuthia, John
Warr, A J
Maleche-Obimbo, Elizabeth
Matemo, Daniel
Cranmer, Lisa M
Escudero, Jaclyn N
Hawn, Thomas R
John-Stewart, Grace C
Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children
title Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children
title_full Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children
title_fullStr Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children
title_full_unstemmed Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children
title_short Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children
title_sort infant tb infection prevention study (itips): a randomised trial protocol evaluating isoniazid to prevent m. tuberculosis infection in hiv-exposed uninfected children
topic Infectious Diseases
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045242/
https://www.ncbi.nlm.nih.gov/pubmed/31969368
http://dx.doi.org/10.1136/bmjopen-2019-034308
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