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BCG Revaccination in Children and Adolescents (BRiC)

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ClinicalTrials.gov Identifier: NCT05330884
Recruitment Status : Not yet recruiting
First Posted : April 15, 2022
Last Update Posted : July 7, 2022
Sponsor:
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
Information provided by (Responsible Party):
Tuberculosis Research Centre, India

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.


Condition or disease Intervention/treatment Phase
Tuberculosis Infection Tuberculosis Biological: BCG vaccine Drug: Oral Chemoprophylaxis Phase 3

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Non-inferiority randomised trial
Masking: None (Open Label)
Primary Purpose: Prevention
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
Estimated Study Start Date : July 15, 2022
Estimated Primary Completion Date : June 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: vaccine - Bacille Calmette-Guérin vaccine (BCG )
Bacille Calmette-Guérin vaccine (BCG ) dose 0.1ml intradermal
Biological: BCG vaccine
0.1ml BCg vaccine to be given intradermally

Chemoprophylaxis - as per NTEP guidelines
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
Drug: Oral Chemoprophylaxis
Oral chemoprophylaxis will be standard of care - either 6 months of Isoniazid or 3 months of weekly Isoniazid and Rifapentine




Primary Outcome Measures :
  1. Incidence of TB (all forms - PTB / EPTB) as per NTEP guidelines [ Time Frame: over 24 months ]
    Incidence of TB in BCG revaccinated and oral chemoprophylaxis groups (age and gender stratified)


Secondary Outcome Measures :
  1. Adverse events [ Time Frame: 24 months ]
    Incidence of adverse events in children in each arm

  2. MTB infection [ Time Frame: 24 months ]
    Incidence of MTB infection in both groups



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05330884


Contacts
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Contact: Aishwarya Venkataraman, MRCPCH +44 2836 9500 ext 9533 venkataraman.a@icmr.gov.in

Sponsors and Collaborators
Tuberculosis Research Centre, India
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
Investigators
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Principal Investigator: Aishwarya Venkataraman, MRCPCH ICMR-National Institute for Research in Tuberculosis
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Responsible Party: Tuberculosis Research Centre, India
ClinicalTrials.gov Identifier: NCT05330884    
Other Study ID Numbers: 2022 005
First Posted: April 15, 2022    Key Record Dates
Last Update Posted: July 7, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by Tuberculosis Research Centre, India:
BCG
Anti tuberculous Chemoprophylaxis
LTBI
TB
Vaccine
Additional relevant MeSH terms:
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Tuberculosis
Latent Tuberculosis
BCG Vaccine
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Latent Infection
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs