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BCG Revaccination in Children and Adolescents (BRiC)

Primary Purpose

Tuberculosis Infection, Tuberculosis

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
BCG vaccine
Oral Chemoprophylaxis
Sponsored by
Tuberculosis Research Centre, India
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Tuberculosis Infection focused on measuring BCG, Anti tuberculous Chemoprophylaxis, LTBI, TB, Vaccine

Eligibility Criteria

6 Years - 18 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy household contacts aged 6 to 18 yr
  • Previously vaccinated with BCG at birth or least 5 years ago - evidence of scar or documented immunisation record.
  • General good health - through history and baseline screening
  • Agrees to continue in the study for 2 years post enrollment
  • Children previously treated for LTBI and completed treatment at least 6 months ago - can also be included. However, they should be current HHC

Exclusion Criteria:

  • Any acute illness on recruitment day (Evaluate the child again at a later stage)
  • Fever ≥38 degree Celsius on recruitment day (Evaluate the child again at a later)
  • History of autoimmune disease
  • Pregnancy - female participants > 15 years of age will have pregnancy test done after caretakers and participants informed consent
  • Evidence of active TB disease
  • On treatment for active TB disease or LTBI
  • HIV positive or any history or present possible immunodeficiency condition
  • History of allergic reactions to vaccines in past
  • Pre-existing liver dysfunction
  • ALT/AST is ≥ 3 times upper limit of normal (ULN) in the presence of symptoms or ≥ 5 times the ULN in the absence of symptoms and/or total bilirubin greater than ULN along with raised ALT/AST.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Other

    Arm Label

    vaccine - Bacille Calmette-Guérin vaccine (BCG )

    Chemoprophylaxis - as per NTEP guidelines

    Arm Description

    Bacille Calmette-Guérin vaccine (BCG ) dose 0.1ml intradermal

    Oral chemoprophylaxis: according to the existing standard of care (NTEP guidelines) Either six months of isoniazid (10mg/kg) or Rifapentine and isoniazid weekly for 3 months for DS TB Levofloxicillin or standard of care drug for DR TB: 15-20mg/kg/day

    Outcomes

    Primary Outcome Measures

    Incidence of TB (all forms - PTB / EPTB) as per NTEP guidelines
    Incidence of TB in BCG revaccinated and oral chemoprophylaxis groups (age and gender stratified)

    Secondary Outcome Measures

    Adverse events
    Incidence of adverse events in children in each arm
    MTB infection
    Incidence of MTB infection in both groups

    Full Information

    First Posted
    March 28, 2022
    Last Updated
    July 4, 2022
    Sponsor
    Tuberculosis Research Centre, India
    Collaborators
    Institute of Child Health, Chennai, All India Institute of Medical Sciences, Guwahati, The Grant Medical College & Sir J.J. Group of Hospitals, All India Institute of Medical Sciences, Bhubaneswar, All India Institute of Medical Sciences, Patna, Rajendra Institute of Medical Sciences, Ranchi, National Institute of Tuberculosis and Respiratory Diseases, New Delhi, Rajiv Gandhi Hospital, Chennai, Madurai Medical College, Government Vellore Medical College, Vellore
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05330884
    Brief Title
    BCG Revaccination in Children and Adolescents
    Acronym
    BRiC
    Official Title
    Efficacy of BCG Revaccination Compared With Oral Chemoprophylaxis in Household Contacts Aged 6-18 Years for Prevention of Tuberculosis Disease - A Phase III Open Labelled Randomised Controlled Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 15, 2022 (Anticipated)
    Primary Completion Date
    June 2025 (Anticipated)
    Study Completion Date
    December 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Tuberculosis Research Centre, India
    Collaborators
    Institute of Child Health, Chennai, All India Institute of Medical Sciences, Guwahati, The Grant Medical College & Sir J.J. Group of Hospitals, All India Institute of Medical Sciences, Bhubaneswar, All India Institute of Medical Sciences, Patna, Rajendra Institute of Medical Sciences, Ranchi, National Institute of Tuberculosis and Respiratory Diseases, New Delhi, Rajiv Gandhi Hospital, Chennai, Madurai Medical College, Government Vellore Medical College, Vellore

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No

    5. Study Description

    Brief Summary
    Bacille Calmette Guerin (BCG) vaccine is one of the most used vaccines of the world, to reduce the risks of natural tuberculous infection. The efficacy of BCG vaccination in newborns is well known and has a documented protective effect against meningitis and disseminated TB in children. However, there is considerable uncertainty on BCG revaccination. It is known that BCG revaccination enhances immune responses, but it is yet to be established if BCG revaccination can help prevent TB disease in household contacts. The primary aim of this study is to assess the efficacy of BCG revaccination compared to oral chemoprophylaxis in preventing TB disease in house hold contacts aged 6-18 years. The study is designed as a multicentre randomised controlled trial with two groups of healthy household contacts aged 6-18 years receiving either the BCG vaccine or oral chemoprophylaxis. They will be followed up for 24 months to compare the incidence of TB disease in each arm.
    Detailed Description
    Objectives Primary: To demonstrate the effect of BCG revaccination in comparison to oral chemoprophylaxis on the incidence of Mycobacterium tuberculosis disease in healthy household contacts aged 6-18 years. Secondary: To compare the safety of BCG revaccination with oral chemoprophylaxis To study the efficacy of BCG revaccination in comparison to oral chemoprophylaxis in preventing Mycobacterium tuberculosis infection To study the immunogenicity of BCG revaccination Methodology The aim of this study is to assess the efficacy of BCG revaccination compared to oral chemoprophylaxis in preventing TB disease in house hold contacts aged 6-18 years. The study is designed as a multicentre randomised controlled trial with two groups of healthy household contacts aged 6-18 years receiving either the BCG vaccine or oral chemoprophylaxis. A total of 9200 children will be recruited across 7 sites in India. Children will be randomised into 2 study arms: 1) BCG; 2) Oral chemoprophylaxis. All children will be household contacts of microbiologically confirmed pulmonary TB patients. Contacts of MDR TB adults will also be included in the study. Both C-Tb skin test positive and negative children will be included. Similarly, both well-nourished and malnourished children will be included. All children will be followed up for 24 months post recruitment and the incidence of TB (all forms - PTB / EPTB) will be compared between the groups. TB will be diagnosed as per the NTEP guidelines and LTBI will be based on the C-TB skin test results. Immunology bloods will be done in 10% of the participants - 920 children at baseline, 3, 6 12 and 24 months. The immunology component of this trial is designed so as to decipher clearly the effects of BCG revaccination on adaptive and innate cell responses. Full Blood Count for Monocyte/Lymphocyte ratio, Whole Blood culture for Intracellular Staining, Innate assays, Mycobacterial Growth Inhibition Assay and acute phase proteins will be performed between groups

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Tuberculosis Infection, Tuberculosis
    Keywords
    BCG, Anti tuberculous Chemoprophylaxis, LTBI, TB, Vaccine

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    Non-inferiority randomised trial
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    9200 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    vaccine - Bacille Calmette-Guérin vaccine (BCG )
    Arm Type
    Experimental
    Arm Description
    Bacille Calmette-Guérin vaccine (BCG ) dose 0.1ml intradermal
    Arm Title
    Chemoprophylaxis - as per NTEP guidelines
    Arm Type
    Other
    Arm Description
    Oral chemoprophylaxis: according to the existing standard of care (NTEP guidelines) Either six months of isoniazid (10mg/kg) or Rifapentine and isoniazid weekly for 3 months for DS TB Levofloxicillin or standard of care drug for DR TB: 15-20mg/kg/day
    Intervention Type
    Biological
    Intervention Name(s)
    BCG vaccine
    Intervention Description
    0.1ml BCg vaccine to be given intradermally
    Intervention Type
    Drug
    Intervention Name(s)
    Oral Chemoprophylaxis
    Intervention Description
    Oral chemoprophylaxis will be standard of care - either 6 months of Isoniazid or 3 months of weekly Isoniazid and Rifapentine
    Primary Outcome Measure Information:
    Title
    Incidence of TB (all forms - PTB / EPTB) as per NTEP guidelines
    Description
    Incidence of TB in BCG revaccinated and oral chemoprophylaxis groups (age and gender stratified)
    Time Frame
    over 24 months
    Secondary Outcome Measure Information:
    Title
    Adverse events
    Description
    Incidence of adverse events in children in each arm
    Time Frame
    24 months
    Title
    MTB infection
    Description
    Incidence of MTB infection in both groups
    Time Frame
    24 months

    10. Eligibility

    Sex
    All
    Gender Based
    Yes
    Minimum Age & Unit of Time
    6 Years
    Maximum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Healthy household contacts aged 6 to 18 yr Previously vaccinated with BCG at birth or least 5 years ago - evidence of scar or documented immunisation record. General good health - through history and baseline screening Agrees to continue in the study for 2 years post enrollment Children previously treated for LTBI and completed treatment at least 6 months ago - can also be included. However, they should be current HHC Exclusion Criteria: Any acute illness on recruitment day (Evaluate the child again at a later stage) Fever ≥38 degree Celsius on recruitment day (Evaluate the child again at a later) History of autoimmune disease Pregnancy - female participants > 15 years of age will have pregnancy test done after caretakers and participants informed consent Evidence of active TB disease On treatment for active TB disease or LTBI HIV positive or any history or present possible immunodeficiency condition History of allergic reactions to vaccines in past Pre-existing liver dysfunction ALT/AST is ≥ 3 times upper limit of normal (ULN) in the presence of symptoms or ≥ 5 times the ULN in the absence of symptoms and/or total bilirubin greater than ULN along with raised ALT/AST.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Aishwarya Venkataraman, MRCPCH
    Phone
    +44 2836 9500
    Ext
    9533
    Email
    venkataraman.a@icmr.gov.in
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Aishwarya Venkataraman, MRCPCH
    Organizational Affiliation
    ICMR-National Institute for Research in Tuberculosis
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

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