BCG Revaccination in Children and Adolescents

NCT ID: NCT05330884

Last Updated: 2023-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE3

Total Enrollment

9200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-15

Study Completion Date

2027-12-31

Brief Summary

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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

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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

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Tuberculosis Infection Tuberculosis

Keywords

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BCG Anti tuberculous Chemoprophylaxis LTBI TB Vaccine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Non-inferiority randomised trial
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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vaccine - Bacille Calmette-Guérin vaccine (BCG )

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

Group Type EXPERIMENTAL

BCG vaccine

Intervention Type BIOLOGICAL

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

Group Type OTHER

Oral Chemoprophylaxis

Intervention Type DRUG

Oral chemoprophylaxis will be standard of care - either 6 months of Isoniazid or 3 months of weekly Isoniazid and Rifapentine

Interventions

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BCG vaccine

0.1ml BCg vaccine to be given intradermally

Intervention Type BIOLOGICAL

Oral Chemoprophylaxis

Oral chemoprophylaxis will be standard of care - either 6 months of Isoniazid or 3 months of weekly Isoniazid and Rifapentine

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

6 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Institute of Child Health, Chennai

UNKNOWN

Sponsor Role collaborator

All India Institute of Medical Sciences

OTHER

Sponsor Role collaborator

The Grant Medical College & Sir J.J. Group of Hospitals

OTHER_GOV

Sponsor Role collaborator

All India Institute of Medical Sciences, Bhubaneswar

OTHER

Sponsor Role collaborator

Rajendra Institute of Medical Sciences, Ranchi

UNKNOWN

Sponsor Role collaborator

National Institute of Tuberculosis and Respiratory Diseases, New Delhi

UNKNOWN

Sponsor Role collaborator

Rajiv Gandhi Hospital, Chennai

UNKNOWN

Sponsor Role collaborator

Madurai Medical College

OTHER

Sponsor Role collaborator

Government Vellore Medical College, Vellore

UNKNOWN

Sponsor Role collaborator

Tuberculosis Research Centre, India

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Aishwarya Venkataraman, MRCPCH

Role: PRINCIPAL_INVESTIGATOR

ICMR-National Institute for Research in Tuberculosis

Locations

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Dr Aishwarya Venkataraman

Chennai, Tamil Nadu, India

Site Status

Countries

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India

Other Identifiers

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2022 005

Identifier Type: -

Identifier Source: org_study_id