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
About this trial
This is an interventional prevention trial for Tuberculosis Infection focused on measuring BCG, Anti tuberculous Chemoprophylaxis, LTBI, TB, Vaccine
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.
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
NCT ID
NCT05330884
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
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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BCG Revaccination in Children and Adolescents
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