Tags

Type your tag names separated by a space and hit enter

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; 10(1):e034308BO

Abstract

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.

Authors+Show Affiliations

Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA sylvial2@uw.edu.Department of Biostatistics, University of Washington, Seattle, Washington, USA. Department of Global Health, University of Washington, Seattle, Washington, USA.Research and Programs, Kenyatta National Hospital, Nairobi, Kenya. Department of Reproductive Health, Kenyatta National Hospital, Nairobi, Kenya.Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.Department of Pediatrics and Child Health, University of Nairobi, Nairobi, Kenya.Research and Programs, Kenyatta National Hospital, Nairobi, Kenya.Department of Pediatrics, Division of Infectious Diseases, Emory University, Atlanta, Georgia, USA. Children's Healthcare of Atlanta Inc, Atlanta, Georgia, USA.Department of Global Health, University of Washington, Seattle, Washington, USA.Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA. Department of Global Health, University of Washington, Seattle, Washington, USA. Department of Epidemiology, University of Washington, Seattle, Washington, USA. Department of Pediatrics, University of Washington, Seattle, Washington, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31969368

Citation

LaCourse, Sylvia M., et al. "Infant TB Infection Prevention Study (iTIPS): a Randomised Trial Protocol Evaluating Isoniazid to Prevent M. Tuberculosis Infection in HIV-exposed Uninfected Children." BMJ Open, vol. 10, no. 1, 2020, pp. e034308.
LaCourse SM, Richardson BA, Kinuthia J, et al. 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;10(1):e034308.
LaCourse, S. M., Richardson, B. A., Kinuthia, J., Warr, A. J., Maleche-Obimbo, E., Matemo, D., ... John-Stewart, G. C. (2020). Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children. BMJ Open, 10(1), pp. e034308. doi:10.1136/bmjopen-2019-034308.
LaCourse SM, et al. 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. PubMed PMID: 31969368.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children. AU - LaCourse,Sylvia M, AU - Richardson,Barbra A, AU - Kinuthia,John, AU - Warr,A J, AU - Maleche-Obimbo,Elizabeth, AU - Matemo,Daniel, AU - Cranmer,Lisa M, AU - Escudero,Jaclyn N, AU - Hawn,Thomas R, AU - John-Stewart,Grace C, Y1 - 2020/01/21/ PY - 2020/1/24/entrez KW - isoniazid KW - pediatric KW - prevention KW - protocol KW - tuberculosis SP - e034308 EP - e034308 JF - BMJ open JO - BMJ Open VL - 10 IS - 1 N2 - 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. SN - 2044-6055 UR - https://www.unboundmedicine.com/medline/citation/31969368/Infant_TB_Infection_Prevention_Study_(iTIPS):_a_randomised_trial_protocol_evaluating_isoniazid_to_prevent_M._tuberculosis_infection_in_HIV-exposed_uninfected_children L2 - http://bmjopen.bmj.com/cgi/pmidlookup?view=long&pmid=31969368 DB - PRIME DP - Unbound Medicine ER -