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Melbourne Infant Study - Bacille Calmette Guérin (BCG) for Allergy & Infection Reduction (MIS BAIR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01906853
Recruitment Status : Active, not recruiting
First Posted : July 24, 2013
Last Update Posted : September 6, 2019
Sponsor:
Collaborators:
Royal Children's Hospital
Mercy Hospital for Women, Australia
University of Melbourne
Information provided by (Responsible Party):
Prof Nigel Curtis, Murdoch Childrens Research Institute

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.

Condition or disease Intervention/treatment Phase
Allergy Eczema Respiratory Tract Infections Biological: BCG Phase 3

Detailed Description:

There has been a dramatic rise in allergic diseases worldwide since the 1980s. Asthma rates increased first, followed by eczema, allergic rhinitis and, more recently, food allergy - especially in infants and young children. In Australia, the prevalence of allergic disease is particularly high: up to 30% of children are affected, and eczema and asthma are among the most common chronic diseases of childhood.

Preventing allergic disease by an immunomodulatory intervention early in life would be a major advance with significant implications for individual health and public health resources. Bacillus Calmette-Guérin (BCG) immunisation is a potential intervention with an established safety profile. This vaccine has powerful non-specific effects on the cellular immune response that potentially prime host immunity away from an allergic pathway. Observational data and one small randomised controlled trial (RCT) suggest that BCG immunisation at birth leads to a substantial reduction in allergic disease - however, there is an absence of level 1 evidence.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1272 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomised, Controlled Trial to Determine if BCG Immunisation at Birth Reduces Allergy and Infection in Infants
Study Start Date : July 2013
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy

Arm Intervention/treatment
No Intervention: No BCG
No BCG
Experimental: BCG
Mycobacterium bovis BCG (Bacille Calmette Guérin) vaccine, Danish Strain 1331
Biological: BCG
Other Names:
  • BCG vaccine - Denmark strain
  • BCG Denmark
  • Statens Serum Institute BCG vaccine
  • Mycobacterium bovis BCG (Bacille Calmette Guérin), Danish Strain 1331




Primary Outcome Measures :
  1. Atopic sensitisation measured by skin prick test (SPT) [ Time Frame: 1 year of age ]
    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

  2. Atopic sensitisation measured by skin prick test (SPT) [ Time Frame: 5 years of age ]
    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

  3. Lower respiratory tract infection (LRTI) [ Time Frame: 0-12 months ]
    Measured by parent report

  4. Lower respiratory tract infection (LRTI) hospital admissions [ Time Frame: 0-5 years of age ]
    Proportion of participants with ≥1 hospital admission for LRTI reported by parent

  5. Eczema ever [ Time Frame: 0-12 months ]
    Proportion of participants with eczema measured by Williams' UK diagnostic criteria using parental report of symptoms

  6. Eczema ever [ Time Frame: 0-5 years of age ]
    Proportion of participants with eczema measured by Williams' UK diagnostic criteria using parental report of symptoms

  7. Current asthma [ Time Frame: 5 years of age ]
    Using ISAAC definitions

  8. Asthma ever [ Time Frame: 5 years of age ]
    Using ISAAC definitions


Secondary Outcome Measures :
  1. Clinical food allergy [ Time Frame: 1 year of age ]
    Proportion of participants with challenge-proven food allergy OR convincing history of food allergy in participants with a SPT wheal diameter ≥1 mm greater than negative control at 15 min to one or more of a panel of food allergens

  2. Clinical food allergy [ Time Frame: 5 years of age ]
    Proportion of participants with challenge-proven food allergy OR convincing history of food allergy in participants with a SPT wheal diameter ≥1 mm greater than negative control at 15 min to one or more of a panel of food allergens

  3. Atopic sensitisation measured by SPT using a more stringent cut-off [ Time Frame: 1 year of age ]
    Proportion of participants with a positive SPT defined as wheal diameter ≥3 mm greater than negative control at 15 min to one or more of a panel of food allergens and aeroallergens

  4. Atopic sensitisation measured by SPT using a more stringent cut-off [ Time Frame: 5 years of age ]
    Proportion of participants with a positive SPT defined as wheal diameter ≥3 mm greater than negative control at 15 min to one or more of a panel of food allergens and aeroallergens

  5. Atopic sensitisation to multiple allergens measured by SPT [ Time Frame: 1 year of age ]
    Proportion of participants with a positive SPT defined as wheal diameter ≥2 mm greater than negative control at 15 min to two or more of a panel of food allergens and aeroallergens

  6. Atopic sensitisation to multiple allergens measured by SPT [ Time Frame: 5 years of age ]
    Proportion of participants with a positive SPT defined as wheal diameter ≥2 mm greater than negative control at 15 min to two or more of a panel of food allergens and aeroallergens

  7. Parent report of food allergy [ Time Frame: 0-12 months of age ]
    Proportion of participants with an allergic reaction to any food reported by parent

  8. Parent report of food allergy [ Time Frame: 0-5 years of age ]
    Proportion of participants with an allergic reaction to any food reported by parent

  9. Egg sensitisation [ Time Frame: 1 year of age ]
    Proportion of participants with a positive SPT defined as wheal diameter ≥2 mm greater than negative control at 15 min to egg allergen

  10. Egg sensitisation [ Time Frame: 5 years of age ]
    Proportion of participants with a positive SPT defined as wheal diameter ≥2 mm greater than negative control at 15 min to egg allergen

  11. Egg allergy [ Time Frame: 1 year of age ]
    Proportion of participants with a challenge-proven egg allergy OR convincing history of egg allergy in participants with a SPT wheal diameter ≥1 mm greater than negative control at 15 min to egg

  12. Egg allergy [ Time Frame: 5 years of age ]
    Proportion of participants with a challenge-proven egg allergy OR convincing history of egg allergy in participants with a SPT wheal diameter ≥1 mm greater than negative control at 15 min to egg

  13. Atopic wheeze [ Time Frame: 1 year of age ]
    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 together with parent-reported wheeze

  14. Atopic wheeze [ Time Frame: 5 years of age ]
    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 together with parent-reported wheeze

  15. Lower respiratory tract infection (LRTI) [ Time Frame: Prior to first Diphtheria, Tetanus, Pertussis (DTP) vaccination ]
    Proportion of participants with ≥1 episode of LRTI, by parental report

  16. Lower respiratory tract infection (LRTI) [ Time Frame: 0-5 years of age ]
    Proportion of participants with ≥1 episode of LRTI, by parental report

  17. Rate of lower respiratory tract infection (LRTI) [ Time Frame: 0-12 months ]
    Number of clinical episodes of LRTI, by parental report

  18. Rate of lower respiratory tract infection (LRTI) [ Time Frame: Prior to first DTP vaccination ]
    Number of clinical episodes of LRTI, by parental report

  19. Rate of lower respiratory tract infection (LRTI) [ Time Frame: 0-5 years of age ]
    Number of clinical episodes of LRTI, by parental report

  20. Infections [ Time Frame: 0-12 months ]
    Hospital admissions for any infection by parental report

  21. Infections [ Time Frame: Prior to first DTP vaccination ]
    Hospital admissions for any infection by parental report

  22. Infections [ Time Frame: 0-5 years of age ]
    Hospital admissions for any infection by parental report

  23. Hospitalisation for respiratory tract infection (RTI) [ Time Frame: 0-12 months of age ]
    Proportion of participants with ≥1 hospital admission for a RTI, by parent report

  24. Hospitalisation for respiratory tract infection (RTI) [ Time Frame: Prior to first DTP vaccination ]
    Proportion of participants with ≥1 hospital admission for a RTI, by parent report

  25. Hospitalisation for respiratory tract infection (RTI) [ Time Frame: 0-5 years of age ]
    Proportion of participants with ≥1 hospital admission for a RTI, by parent report

  26. Rate of any infection [ Time Frame: 0-12 months of age ]
    Number of clinical episodes of where an infant had symptoms of: wheeze, rattle/rattly chest, fever, runny/blocked nose, cough, or diarrhoea (with vomiting), by parent report

  27. Rate of any infection [ Time Frame: Prior to first DTP vaccination ]
    Number of clinical episodes of where an infant had symptoms of: wheeze, rattle/rattly chest, fever, runny/blocked nose, cough, or diarrhoea (with vomiting), by parent report

  28. Rate of upper respiratory tract infection (URTI) [ Time Frame: 0-12 months of age ]
    Number of clinical episodes of upper respiratory tract infections, by parent report

  29. Rate of upper respiratory tract infection (URTI) [ Time Frame: Prior to first DTP vaccination ]
    Number of clinical episodes of upper respiratory tract infections, by parent report

  30. Rate of fever [ Time Frame: 0-12 months of age ]
    Number of clinical episodes of fever, by parent report

  31. Rate of fever [ Time Frame: Prior to first DTP vaccination ]
    Number of clinical episodes of fever, by parent report

  32. Diarrhoea [ Time Frame: 0-12 months of age ]
    Proportion of participants with ≥1 episodes of diarrhoea

  33. Diarrhoea [ Time Frame: Prior to first DTP vaccination ]
    Proportion of participants with ≥1 episodes of diarrhoea

  34. Rash with fever [ Time Frame: 0-12 months of age ]
    Proportion of participants with ≥1 episodes of rash with fever

  35. Rash with fever [ Time Frame: Prior to first DTP vaccination ]
    Proportion of participants with ≥1 episodes of rash with fever

  36. Eczema ever [ Time Frame: 0-12 months of age ]
    Proportion of participants with eczema measured by a combined eczema measure

  37. Eczema ever [ Time Frame: 0-5 years of age ]
    Proportion of participants with eczema measured by a combined eczema measure

  38. Eczema [ Time Frame: 0-12 months ]
    Proportion of clinician-diagnosed eczema, by parental report

  39. Eczema [ Time Frame: 0-5 years of age ]
    Proportion of clinician-diagnosed eczema, by parental report

  40. Eczema onset [ Time Frame: 0-12 months ]
    Age of onset of eczema, by parental report

  41. Eczema onset [ Time Frame: 0-5 years of age ]
    Age of onset of eczema, by parental report

  42. Eczema severity [ Time Frame: 0-12 months ]
    Measured by parental report (POEM score)

  43. Eczema severity [ Time Frame: 0-12 months ]
    Measured by clinical assessment (SCORAD)

  44. Eczema severity [ Time Frame: 0-12 months ]
    Eczema medication use, by parental report

  45. Eczema severity [ Time Frame: 0-5 years of age ]
    Measured by parental report (POEM score)

  46. Eczema severity [ Time Frame: 0-5 years of age ]
    Measured by clinical assessment (SCORAD)

  47. Eczema severity [ Time Frame: 0-5 years of age ]
    Eczema medication use, by parental report

  48. Asthma severity [ Time Frame: 4 years of age ]
    Measured by asthma control test (ACT), by parental/participant report

  49. Asthma severity [ Time Frame: 5 years of age ]
    Measured by asthma control test (ACT), by parental/participant report

  50. Asthma severity [ Time Frame: 2-5 years of age ]
    Hospital admissions for asthma, by parental report

  51. Laboratory measures of the immune response [ Time Frame: Time Frame: 0-5 years of age ]

Other Outcome Measures:
  1. Effect of sex on the non-specific effects BCG [ Time Frame: 0-12 months and 0-5 years of age ]
    Sub-group analysis

  2. Effect of maternal BCG on the non-specific effects BCG [ Time Frame: 0-12 months and 0-5 years of age ]
    Sub-group analysis

  3. Effect of presence or absence BCG scar on the non-specific effects of BCG [ Time Frame: 0-12 months and 0-5 years of age ]
    Sub-group analysis

  4. Effect of timing of BCG administration on the non-specific effects BCG [ Time Frame: 0-12 months and 0-5 years of age ]
    Sub-group analysis

  5. Effect of mode of delivery on the non-specific effects BCG [ Time Frame: 0-12 months and 0-5 years of age ]
    Sub-group analysis

  6. Effect of family history of allergy on the allergy and eczema outcomes [ Time Frame: 0-12 months and 0-5 years of age ]
    Sub-group analysis

  7. Effect of season of birth on the non-specific effects BCG [ Time Frame: 0-12 months and 0-5 years of age ]
    Sub-group analysis

  8. Effect of hepatitis B vaccine timing birth on the non-specific effects BCG [ Time Frame: 0-12 months and 0-5 years of age ]
    Sub-group analysis

  9. Meta-analysis [ Time Frame: 36 months ]
    Joint meta-analysis with data from the Danish Calmette study (NCT01694108)

  10. Morbidity [ Time Frame: 0-12 months of age ]
    Hospital admissions for any reason by parental report

  11. Morbidity [ Time Frame: 0-5 years of age ]
    Hospital admissions for any reason by parental report



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 10 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

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.

Information from the National Library of Medicine

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): NCT01906853


Locations
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Australia, Victoria
Mercy Hospital for Women
Heidelberg, Victoria, Australia, 3084
Royal Children's Hospital
Melbourne, Victoria, Australia, 3052
Sponsors and Collaborators
Murdoch Childrens Research Institute
Royal Children's Hospital
Mercy Hospital for Women, Australia
University of Melbourne
Investigators
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Principal Investigator: Prof Nigel Curtis, MBBS DCH DTM&H MRCP FRCPCH PhD Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Prof Nigel Curtis, Murdoch Childrens Research Institute
ClinicalTrials.gov Identifier: NCT01906853    
Other Study ID Numbers: BCG12/01
1051228 ( Other Grant/Funding Number: National Health and Medical Research Council (NHMRC) )
First Posted: July 24, 2013    Key Record Dates
Last Update Posted: September 6, 2019
Last Verified: September 2019
Keywords provided by Prof Nigel Curtis, Murdoch Childrens Research Institute:
BCG
Bacille Calmette Guérin
Allergy
Immunity
Immune response
Vaccine
Infants
Children
Infection
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Respiratory Tract Infections
Hypersensitivity
Immune System Diseases
Respiratory Tract Diseases
Vaccines
BCG Vaccine
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic