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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01906853




Registration number
NCT01906853
Ethics application status
Date submitted
21/07/2013
Date registered
24/07/2013
Date last updated
8/07/2024

Titles & IDs
Public title
Melbourne Infant Study - Bacille Calmette Guérin (BCG) for Allergy & Infection Reduction
Scientific title
A Randomised, Controlled Trial to Determine if BCG Immunisation at Birth Reduces Allergy and Infection in Infants
Secondary ID [1] 0 0
1051228
Secondary ID [2] 0 0
BCG12/01
Universal Trial Number (UTN)
Trial acronym
MIS BAIR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Allergy 0 0
Eczema 0 0
Respiratory Tract Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
No intervention: No BCG - No BCG

Experimental: BCG - Mycobacterium bovis BCG (Bacille Calmette Guérin) vaccine, Danish Strain 1331
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Atopic sensitisation measured by skin prick test (SPT)
Timepoint [1] 0 0
1 year of age
Primary outcome [2] 0 0
Atopic sensitisation measured by skin prick test (SPT)
Timepoint [2] 0 0
5 years of age
Primary outcome [3] 0 0
Lower respiratory tract infection (LRTI)
Timepoint [3] 0 0
0-12 months
Primary outcome [4] 0 0
Lower respiratory tract infection (LRTI) hospital admissions
Timepoint [4] 0 0
0-5 years of age
Primary outcome [5] 0 0
Eczema ever
Timepoint [5] 0 0
0-12 months
Primary outcome [6] 0 0
Eczema ever
Timepoint [6] 0 0
0-5 years of age
Primary outcome [7] 0 0
Current asthma
Timepoint [7] 0 0
5 years of age
Primary outcome [8] 0 0
Asthma ever
Timepoint [8] 0 0
5 years of age
Secondary outcome [1] 0 0
Clinical food allergy
Timepoint [1] 0 0
1 year of age
Secondary outcome [2] 0 0
Clinical food allergy
Timepoint [2] 0 0
5 years of age
Secondary outcome [3] 0 0
Atopic sensitisation measured by SPT using a more stringent cut-off
Timepoint [3] 0 0
1 year of age
Secondary outcome [4] 0 0
Atopic sensitisation measured by SPT using a more stringent cut-off
Timepoint [4] 0 0
5 years of age
Secondary outcome [5] 0 0
Atopic sensitisation to multiple allergens measured by SPT
Timepoint [5] 0 0
1 year of age
Secondary outcome [6] 0 0
Atopic sensitisation to multiple allergens measured by SPT
Timepoint [6] 0 0
5 years of age
Secondary outcome [7] 0 0
Parent report of food allergy
Timepoint [7] 0 0
0-12 months of age
Secondary outcome [8] 0 0
Parent report of food allergy
Timepoint [8] 0 0
0-5 years of age
Secondary outcome [9] 0 0
Egg sensitisation
Timepoint [9] 0 0
1 year of age
Secondary outcome [10] 0 0
Egg sensitisation
Timepoint [10] 0 0
5 years of age
Secondary outcome [11] 0 0
Egg allergy
Timepoint [11] 0 0
1 year of age
Secondary outcome [12] 0 0
Egg allergy
Timepoint [12] 0 0
5 years of age
Secondary outcome [13] 0 0
Atopic wheeze
Timepoint [13] 0 0
1 year of age
Secondary outcome [14] 0 0
Atopic wheeze
Timepoint [14] 0 0
5 years of age
Secondary outcome [15] 0 0
Lower respiratory tract infection (LRTI)
Timepoint [15] 0 0
Prior to first Diphtheria, Tetanus, Pertussis (DTP) vaccination
Secondary outcome [16] 0 0
Lower respiratory tract infection (LRTI)
Timepoint [16] 0 0
0-5 years of age
Secondary outcome [17] 0 0
Rate of lower respiratory tract infection (LRTI)
Timepoint [17] 0 0
0-12 months
Secondary outcome [18] 0 0
Rate of lower respiratory tract infection (LRTI)
Timepoint [18] 0 0
Prior to first DTP vaccination
Secondary outcome [19] 0 0
Rate of lower respiratory tract infection (LRTI)
Timepoint [19] 0 0
0-5 years of age
Secondary outcome [20] 0 0
Infections
Timepoint [20] 0 0
0-12 months
Secondary outcome [21] 0 0
Infections
Timepoint [21] 0 0
Prior to first DTP vaccination
Secondary outcome [22] 0 0
Infections
Timepoint [22] 0 0
0-5 years of age
Secondary outcome [23] 0 0
Hospitalisation for respiratory tract infection (RTI)
Timepoint [23] 0 0
0-12 months of age
Secondary outcome [24] 0 0
Hospitalisation for respiratory tract infection (RTI)
Timepoint [24] 0 0
Prior to first DTP vaccination
Secondary outcome [25] 0 0
Hospitalisation for respiratory tract infection (RTI)
Timepoint [25] 0 0
0-5 years of age
Secondary outcome [26] 0 0
Rate of any infection
Timepoint [26] 0 0
0-12 months of age
Secondary outcome [27] 0 0
Rate of any infection
Timepoint [27] 0 0
Prior to first DTP vaccination
Secondary outcome [28] 0 0
Rate of upper respiratory tract infection (URTI)
Timepoint [28] 0 0
0-12 months of age
Secondary outcome [29] 0 0
Rate of upper respiratory tract infection (URTI)
Timepoint [29] 0 0
Prior to first DTP vaccination
Secondary outcome [30] 0 0
Rate of fever
Timepoint [30] 0 0
0-12 months of age
Secondary outcome [31] 0 0
Rate of fever
Timepoint [31] 0 0
Prior to first DTP vaccination
Secondary outcome [32] 0 0
Diarrhoea
Timepoint [32] 0 0
0-12 months of age
Secondary outcome [33] 0 0
Diarrhoea
Timepoint [33] 0 0
Prior to first DTP vaccination
Secondary outcome [34] 0 0
Rash with fever
Timepoint [34] 0 0
0-12 months of age
Secondary outcome [35] 0 0
Rash with fever
Timepoint [35] 0 0
Prior to first DTP vaccination
Secondary outcome [36] 0 0
Eczema ever
Timepoint [36] 0 0
0-12 months of age
Secondary outcome [37] 0 0
Eczema ever
Timepoint [37] 0 0
0-5 years of age
Secondary outcome [38] 0 0
Eczema
Timepoint [38] 0 0
0-12 months
Secondary outcome [39] 0 0
Eczema
Timepoint [39] 0 0
0-5 years of age
Secondary outcome [40] 0 0
Eczema onset
Timepoint [40] 0 0
0-12 months
Secondary outcome [41] 0 0
Eczema onset
Timepoint [41] 0 0
0-5 years of age
Secondary outcome [42] 0 0
Eczema severity
Timepoint [42] 0 0
0-12 months
Secondary outcome [43] 0 0
Eczema severity
Timepoint [43] 0 0
0-12 months
Secondary outcome [44] 0 0
Eczema severity
Timepoint [44] 0 0
0-12 months
Secondary outcome [45] 0 0
Eczema severity
Timepoint [45] 0 0
0-5 years of age
Secondary outcome [46] 0 0
Eczema severity
Timepoint [46] 0 0
0-5 years of age
Secondary outcome [47] 0 0
Eczema severity
Timepoint [47] 0 0
0-5 years of age
Secondary outcome [48] 0 0
Asthma severity
Timepoint [48] 0 0
4 years of age
Secondary outcome [49] 0 0
Asthma severity
Timepoint [49] 0 0
5 years of age
Secondary outcome [50] 0 0
Asthma severity
Timepoint [50] 0 0
2-5 years of age
Secondary outcome [51] 0 0
Laboratory measures of the immune response
Timepoint [51] 0 0
Time Frame: 0-5 years of age

Eligibility
Key inclusion criteria
Inclusion criteria:

* 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.
Minimum age
No limit
Maximum age
10 Days
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria:

* 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;
* Family history of immunodeficiency;
* Consanguineous parents;
* Multiple births more than twins.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/12/2024
Actual
Sample size
Target
Accrual to date
Final
1272
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [2] 0 0
Royal Children's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3052 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Royal Children's Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Mercy Hospital for Women, Australia
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
University of Melbourne
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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. 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 website
https://clinicaltrials.gov/study/NCT01906853
Trial related presentations / publications
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Prof Nigel Curtis, MBBS DCH DTM&H MRCP FRCPCH PhD
Address 0 0
Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01906853