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Completed

NCT Number: NCT01906853

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

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.

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Key information

Conditions

Allergy Dermatitis Eczema Hypersensitivity Immune System Diseases Infections Respiratory Tract Diseases Respiratory Tract Infections Skin Diseases Skin Diseases, Eczematous Skin and Connective Tissue Diseases

Age range

Up to 10 day

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Mercy Hospital for Women, Heidelberg, Victoria, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

BCG

Biological

Other names: BCG vaccine - Denmark strain, BCG Denmark, Statens Serum Institute BCG vaccine, Mycobacterium bovis BCG (Bacille Calmette Guérin), Danish Strain 1331

Primary outcomes

  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 outcomes

  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 ≥2 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 ≥2 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 ≥2 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 ≥2 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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Murdoch Childrens Research Institute

Other

Collaborators

  • Mercy Hospital for Women, Australia
  • Royal Children's Hospital
  • University of Melbourne

Registry information

Official study title

A Randomised, Controlled Trial to Determine if BCG Immunisation at Birth Reduces Allergy and Infection in Infants

Acronym: MIS BAIR

Important dates

Study start
2013
Primary completion
2023
Study completion
2025
First posted
Jul 24, 2013
Registry last updated
Feb 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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