NCT01906853

Brief Summary

  1. 1.To determine if BCG immunisation at birth, compared to no BCG immunisation, leads to a reduction in measures of allergy and infection in the first 12 months of life.
  2. 2.To evaluate the immunological mechanisms underlying the non-specific effects of BCG by comparing markers of immunity between the BCG and non-BCG groups.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,272

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jul 2013

Longer than P75 for phase_3

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2013

Completed
20 days until next milestone

First Submitted

Initial submission to the registry

July 21, 2013

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 24, 2013

Completed
10.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2023

Completed
1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2025

Completed
Last Updated

February 17, 2025

Status Verified

February 1, 2025

Enrollment Period

10.2 years

First QC Date

July 21, 2013

Last Update Submit

February 13, 2025

Conditions

AllergyEczemaRespiratory Tract Infections

Keywords

BCGBacille Calmette GuérinAllergyImmunityImmune responseVaccineInfantsChildrenInfection

Outcome Measures

Primary Outcomes (8)

  • Atopic sensitisation measured by skin prick test (SPT)

    Proportion of participants with a positive SPT defined as wheal diameter ≥2 mm greater than negative control at 15 min to one or more of a panel of food and aeroallergens

    1 year of age

  • Atopic sensitisation measured by skin prick test (SPT)

    Proportion of participants with a positive SPT defined as wheal diameter ≥2 mm greater than negative control at 15 min to one or more of a panel of food and aeroallergens

    5 years of age

  • Lower respiratory tract infection (LRTI)

    Measured by parent report

    0-12 months

  • Lower respiratory tract infection (LRTI) hospital admissions

    Proportion of participants with ≥1 hospital admission for LRTI reported by parent

    0-5 years of age

  • Eczema ever

    Proportion of participants with eczema measured by Williams' UK diagnostic criteria using parental report of symptoms

    0-12 months

  • Eczema ever

    Proportion of participants with eczema measured by Williams' UK diagnostic criteria using parental report of symptoms

    0-5 years of age

  • Current asthma

    Using ISAAC definitions

    5 years of age

  • Asthma ever

    Using ISAAC definitions

    5 years of age

Secondary Outcomes (51)

  • Clinical food allergy

    1 year of age

  • Clinical food allergy

    5 years of age

  • Atopic sensitisation measured by SPT using a more stringent cut-off

    1 year of age

  • Atopic sensitisation measured by SPT using a more stringent cut-off

    5 years of age

  • Atopic sensitisation to multiple allergens measured by SPT

    1 year of age

  • +46 more secondary outcomes

Other Outcomes (11)

  • Effect of sex on the non-specific effects BCG

    0-12 months and 0-5 years of age

  • Effect of maternal BCG on the non-specific effects BCG

    0-12 months and 0-5 years of age

  • Effect of presence or absence BCG scar on the non-specific effects of BCG

    0-12 months and 0-5 years of age

  • +8 more other outcomes

Study Arms (2)

No BCG

NO INTERVENTION

No BCG

BCG

EXPERIMENTAL

Mycobacterium bovis BCG (Bacille Calmette Guérin) vaccine, Danish Strain 1331

Biological: BCG

Interventions

BCGBIOLOGICAL
Also known as: BCG vaccine - Denmark strain, BCG Denmark, Statens Serum Institute BCG vaccine, Mycobacterium bovis BCG (Bacille Calmette Guérin), Danish Strain 1331
BCG

Eligibility Criteria

AgeUp to 10 Days
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • Less than 10 days old;
  • English speaking mother;
  • An informed consent form must be signed and dated by their parent(s) or legally acceptable representative after the nature of the study has been explained and prior to any study assessments/procedures;
  • The infant's mother has screened negative for HIV during this pregnancy;
  • Born no earlier than eight weeks before estimated date of delivery;
  • Birth weight \>1500g.
  • The legal guardian expects to be able to complete four online/phone questionnaires over the infant's first 12 months of life and for the infant to be available for skin prick testing at RCH between 12-16 months of age.

You may not qualify if:

  • Any indication for BCG immunisation in the first 12 months of life including:
  • likely travel to a high tuberculosis (TB) incidence country in the first year of life.
  • Aboriginal and Torres Strait Islander babies living in parts of Australia where the incidence of TB is higher
  • newborn babies, if either parent has leprosy or a family history of leprosy
  • newborn in contact with a patient with TB.
  • Known or suspected HIV infection
  • Treatment with corticosteroids or other immunosuppressive therapy, including monoclonal antibodies against tumour necrosis factor-alpha (TNF-alpha) (e.g. infliximab, etanercept, adalimumab).
  • Born to a mother treated with bDMARDS (e.g. TNF-alpha blocking monoclonal antibodies) in the 3rd trimester;
  • Congenital cellular immunodeficiencies including specific deficiencies of the interferon gamma pathway;
  • Malignancies involving bone marrow or lymphoid systems;
  • Serious underlying illness including severe malnutrition;
  • Medically unstable;
  • Generalised septic skin disease and skin conditions such as eczema, dermatitis and psoriasis;
  • Significant febrile illness;
  • Mother immunosuppressed;
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Mercy Hospital for Women

Heidelberg, Victoria, 3084, Australia

Location

Royal Children's Hospital

Melbourne, Victoria, 3052, Australia

Location

Related Publications (8)

  • Khazaei Y, Kodikara S, Butler CA, Messina NL, Le Cao KA, Dashper SG, Silva MJ. Development and validation of diagnostic and prognostic prediction tools for dental caries in young children through prospective and cross-sectional observational studies: a protocol. BMJ Open. 2025 Oct 5;15(10):e105145. doi: 10.1136/bmjopen-2025-105145.

    PMID: 41047269DERIVED

  • Pittet LF, Forbes EK, Donath S, Francis KL, Gardiner K, Flanagan KL, Ponsonby AL, Robins-Browne R, Shann F, South M, Vuillermin P, Casalaz D, Curtis N, Messina NL; Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR) Group. Neonatal BCG vaccination to prevent asthma: Results from the MIS BAIR randomized controlled trial. Pediatr Allergy Immunol. 2025 Jun;36(6):e70110. doi: 10.1111/pai.70110.

    PMID: 40464744DERIVED

  • Messina NL, Gardiner K, Pittet LF, Forbes EK, Francis KL, Freyne B, Zufferey C, Abruzzo V, Morison C, Turner H, Allen KJ, Flanagan KL, Ponsonby AL, Robins-Browne R, Shann F, Vuillermin P, Donath S, Casalaz D, Curtis N; Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR) Group. Neonatal BCG Vaccination for Prevention of Allergy in Infants: The MIS BAIR Randomised Controlled Trial. Clin Exp Allergy. 2024 Sep;54(9):682-693. doi: 10.1111/cea.14537. Epub 2024 Jul 14.

    PMID: 39004434DERIVED

  • Pittet LF, Messina NL, Gardiner K, Freyne B, Abruzzo V, Morrison C, Vuillermin P, Allen KJ, Ponsonby AL, Robins-Browne R, Shann F, Flanagan KL, Donath S, Casalaz D, Phillips R, Curtis N. Discordance Between Diagnosis Tools for Assessing Eczema in Infants: A Challenge for Intervention Trials. Dermatitis. 2022 May-Jun 01;33(3):207-214. doi: 10.1097/DER.0000000000000842. Epub 2022 Feb 16.

    PMID: 35170523DERIVED

  • Pittet LF, Messina NL, Gardiner K, Freyne B, Abruzzo V, Francis KL, Morrison C, Zufferey C, Vuillermin P, Allen KJ, Ponsonby AL, Robins-Browne R, Shann F, Flanagan KL, Phillips R, Donath S, Casalaz D, Curtis N. Prevention of infant eczema by neonatal Bacillus Calmette-Guerin vaccination: The MIS BAIR randomized controlled trial. Allergy. 2022 Mar;77(3):956-965. doi: 10.1111/all.15022. Epub 2021 Aug 9.

    PMID: 34309859DERIVED

  • Cirovic B, de Bree LCJ, Groh L, Blok BA, Chan J, van der Velden WJFM, Bremmers MEJ, van Crevel R, Handler K, Picelli S, Schulte-Schrepping J, Klee K, Oosting M, Koeken VACM, van Ingen J, Li Y, Benn CS, Schultze JL, Joosten LAB, Curtis N, Netea MG, Schlitzer A. BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment. Cell Host Microbe. 2020 Aug 12;28(2):322-334.e5. doi: 10.1016/j.chom.2020.05.014. Epub 2020 Jun 15.

    PMID: 32544459DERIVED

  • Messina NL, Gardiner K, Donath S, Flanagan K, Ponsonby AL, Shann F, Robins-Browne R, Freyne B, Abruzzo V, Morison C, Cox L, Germano S, Zufferey C, Zimmermann P, Allen KJ, Vuillermin P, South M, Casalaz D, Curtis N. Study protocol for the Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR), a randomised controlled trial to determine the non-specific effects of neonatal BCG vaccination in a low-mortality setting. BMJ Open. 2019 Dec 15;9(12):e032844. doi: 10.1136/bmjopen-2019-032844.

    PMID: 31843845DERIVED

  • Zimmermann P, Perrett KP, van der Klis FR, Curtis N. The immunomodulatory effects of measles-mumps-rubella vaccination on persistence of heterologous vaccine responses. Immunol Cell Biol. 2019 Jul;97(6):577-585. doi: 10.1111/imcb.12246. Epub 2019 Mar 28.

    PMID: 30791143DERIVED

MeSH Terms

Conditions

HypersensitivityEczemaRespiratory Tract InfectionsInfections

Interventions

BCG Vaccine

Condition Hierarchy (Ancestors)

Immune System DiseasesDermatitisSkin DiseasesSkin and Connective Tissue DiseasesSkin Diseases, EczematousRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Tuberculosis VaccinesBacterial VaccinesVaccinesBiological ProductsComplex Mixtures

Study Officials

  • Prof Nigel Curtis, MBBS DCH DTM&H MRCP FRCPCH PhD

    Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 21, 2013

First Posted

July 24, 2013

Study Start

July 1, 2013

Primary Completion

September 1, 2023

Study Completion

February 1, 2025

Last Updated

February 17, 2025

Record last verified: 2025-02

Locations

AU(2)