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
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|
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.
- 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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||9200 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Non-inferiority randomised trial|
|Masking:||None (Open Label)|
|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|
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
- 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)
- Adverse events [ Time Frame: 24 months ]Incidence of adverse events in children in each arm
- MTB infection [ Time Frame: 24 months ]Incidence of MTB infection in both groups
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
|Contact: Aishwarya Venkataraman, MRCPCH||+44 2836 9500 ext firstname.lastname@example.org|
|Principal Investigator:||Aishwarya Venkataraman, MRCPCH||ICMR-National Institute for Research in Tuberculosis|