Tuberculosis InfectionPhase 3BRiCNCT05330884
BCG Revaccination in Children and Adolescents
A Phase 3 study testing BCG vaccine and Oral Chemoprophylaxis in people with Tuberculosis Infection and Tuberculosis, run by Tuberculosis Research Centre, India at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis Infection, Tuberculosis
- What is being tested?
- BCG vaccine and Oral Chemoprophylaxis
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9,200 participants
- Where
- 1 siteIndia
- Study dates
- 15 Jul 2024to Dec 2027
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Conditions
- Tuberculosis Infection, Tuberculosis
- Being tested
- BCG vaccine, Oral Chemoprophylaxis
- Keywords
- BCG, Anti tuberculous Chemoprophylaxis, LTBI, TB, Vaccine
- Medical subject headings
- Latent Tuberculosis, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG vaccineBiological
0.1ml BCg vaccine to be given intradermally
Oral ChemoprophylaxisDrug
Oral chemoprophylaxis will be standard of care - either 6 months of Isoniazid or 3 months of weekly Isoniazid and Rifapentine
| Study group | Role | What they receive |
|---|---|---|
| vaccine - Bacille Calmette-Guérin vaccine (BCG ) | Experimental | Bacille Calmette-Guérin vaccine (BCG ) dose 0.1ml intradermal Receives: Biological: BCG vaccine |
| Chemoprophylaxis - as per NTEP guidelines | Other | 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 Receives: Drug: Oral Chemoprophylaxis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: over 24 months
Secondary outcomes (2)
Adverse events
Incidence of adverse events in children in each arm
Measured: 24 months
MTB infection
Incidence of MTB infection in both groups
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2022
- Study start15 Jul 2024 (estimated)
- Primary completionJun 2027 (estimated)
- Study completionDec 2027 (estimated)
Why it stopped: changes in protocol
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Non-inferiority randomised trial
- Masking
- None (open label)
- Enrolment
- 9,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tuberculosis Research Centre, India
- Sponsor type
- Other government
- Collaborators
- Institute of Child Health, Chennai, All India Institute of Medical Sciences, The Grant Medical College & Sir J.J. Group of Hospitals, All India Institute of Medical Sciences, Bhubaneswar, 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
- Responsible party
- Sponsor
- Investigators
- Aishwarya Venkataraman, MRCPCH, Principal investigator, ICMR-National Institute for Research in Tuberculosis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05330884
- Sponsor's protocol ID
- 2022 005
- Acronym
- BRiC
- Status last verified
- Dec 2023
- First submitted
- 28 Mar 2022
- Last updated
- 18 Dec 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05330884
- Acronym / sponsor ID
- BRiC / 2022 005
- Conditions
- Tuberculosis Infection, Tuberculosis
- Keywords
- BCG, Anti tuberculous Chemoprophylaxis, LTBI, TB, Vaccine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: changes in protocol
- Enrolment
- 9,200 participants (estimated)
- Lead sponsor
- Tuberculosis Research Centre, IndiaOther government
- Collaborators
- Institute of Child Health, Chennai, All India Institute of Medical Sciences, The Grant Medical College & Sir J.J. Group of Hospitals, All India Institute of Medical Sciences, Bhubaneswar, 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
- Study start
- 15 Jul 2024 (estimated)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 15 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Non-inferiority randomised trial
| Arm | Type | Receives |
|---|---|---|
| vaccine - Bacille Calmette-Guérin vaccine (BCG ) | Experimental | Biological: BCG vaccineBacille Calmette-Guérin vaccine (BCG ) dose 0.1ml intradermal |
| Chemoprophylaxis - as per NTEP guidelines | Other | Drug: Oral ChemoprophylaxisOral 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 |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCG vaccine0.1ml BCg vaccine to be given intradermally | Biological | vaccine - Bacille Calmette-Guérin vaccine (BCG ) |
| Oral ChemoprophylaxisOral chemoprophylaxis will be standard of care - either 6 months of Isoniazid or 3 months of weekly Isoniazid and Rifapentine | Drug | Chemoprophylaxis - as per NTEP guidelines |
Primary outcome
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)
2 secondary outcomes
Adverse events
Time frame: 24 months
MTB infection
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aishwarya Venkataraman, MRCPCH principal investigator
ICMR-National Institute for Research in Tuberculosis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BCG vaccine and Oral Chemoprophylaxis in people with Tuberculosis Infection and Tuberculosis, run by Tuberculosis Research Centre, India at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 18 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of TB (all forms - PTB / EPTB) as per NTEP guidelines (time frame: over 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2023.