Overview

This trial is active, not recruiting.

Conditions prospective, single-blind, clinical, trial, intervention
Treatment bcg-vaccine (ssi)
Phase phase 4
Sponsor Lone Graff Stensballe
Collaborator Hvidovre University Hospital
Start date September 2012
End date September 2015
Trial size 4300 participants
Trial identifier NCT01694108, EudraCT2010-021979-85

Summary

In high-income societies the use of health care and medication is steadily increasing. Children have high morbidity, many visits at the general practitioner, an increasing number of hospitalisations, and an increasing use of medication. And, when children are ill, someone has to stay home to care for them. An un-explained global increase in the incidence of the allergic diseases eczema, wheezing, asthma and allergies means that 25% of high-income populations are affected. Cheap preventive measures are highly warranted. Recent studies have shown a positive, non-specific effect of early Bacille Calmette Guérin (BCG) immunisation on neonatal mortality in low-income countries and suggested a positive, non-specific effect on allergic disease in high-income countries. "Non-specific" means that the vaccine effect goes beyond prevention of the targeted disease, i.e. the BCG vaccine benefits the health status of the immunised individual in ways unrelated to protection against tuberculosis (TB). For instance, in a recent randomised trial in West Africa the investigators showed that the BCG vaccine at birth was safe in low birth weight (LBW) infants and significantly reduced neonatal mortality in these children, with a significant long-lasting effect on infant mortality in the smallest newborns with a birth weight <1.5 kg. There is an urgent need to explore the huge potential of the BCG's beneficial immune-stimulatory effects among children in high-income populations.

Therefore, the investigators will carry out a large prospective randomised clinical trial in Denmark primarily designed to test the hypothesis that infants who get the BCG vaccine at birth experience 20% fewer hospitalisations during early childhood.

Secondary outcomes

1. To test the hypothesis that infants who get the BCG vaccine at birth are prescribed less antibiotics during early childhood than non-BCG-immunised infants.

2. To test the hypothesis that Danish infants who get the BCG vaccine at birth develop less eczema, asthmatic bronchitis/wheeze and food allergy at 3 and 12 months of age: self-reported, diagnosed by a physician, or found at clinical examination; and are prescribed less anti-eczema/asthma/allergy medication during early childhood than non-BCG-immunised infants.

3. To test the hypothesis that infants who receive the BCG at birth respond in paraclinical measures: Specific IgE, thymic gland size, leucocyte count and differentiation, monocyte memory, cytokine profiles, and antibody titres following immunisation against diphtheria, tetanus, pertussis, pneumococcus, hemophilus.

4. To test the hypothesis that infants who get the BCG vaccine at birth respond in growth measures: weight, length and head circumference.

5. To test the hypothesis that infants who get the BCG vaccine at birth respond with decreased morbidity: common cold, pneumonia, febrile episodes, diarrhoea and vomiting, acute otitis media, febrile convulsions.

6. To test the hypothesis that premature infants with gestational age less than 37 weeks who get the BCG vaccine at birth have unaffected psychomotor development measures: Ages and Stages scores.

7. To test the hypothesis that infants who get the BCG vaccine at birth has unaffected coverage with the subsequent vaccinations in the Child Vaccination Programme.

8. To test the above mentioned hypotheses specifically in the strata of premature and low-birth-weight Danish infants.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model single group assignment
Masking single blind (outcomes assessor)
Primary purpose prevention
Arm
(Experimental)
Children born to mothers, who have accepted to participate, will be randomised to either intervention group or to the control group at birth. Block‐randomisation stratified by hospital, gender and gestational age (≥37 weeks of gestation vs. < 37 weeks of gestation) will be performed electronically just before vaccination by the overall study electronic case report system (e‐crf). Children randomised to the BCG vaccination group will receive an intradermal BCG vaccine (Statens Serum Institute "CG vaccine" in the standard dose 0.05 ml in the upper, lateral part of the arm of the child by a specially trained midwife or a study physician.
bcg-vaccine (ssi)
(No Intervention)
Control children will be treated as usual, since no suitable placebo exists.

Primary Outcomes

Measure
Hospitalisations
time frame: 0-2 years of age

Secondary Outcomes

Measure
Antibiotics
time frame: 0-2 years of age
Eczema
time frame: 0-13 months of age
Specific IgE
time frame: 13 months of age
Weight
time frame: 0-13 months of age
Psychomotor development in premature infants
time frame: 0-13 months of age
Vaccination coverage
time frame: 0-13 months of age
Premature infants
time frame: 0-2 years of age
Asthma
time frame: 0-13 months
Food allergy
time frame: 0-13 months
Length
time frame: 0-13months
Head circumference
time frame: 0-13months
Thymic gland size
time frame: 0-13 months of age
Leucocyte count and differentiation
time frame: 0-13 months of age
Monocyte memory
time frame: 0-13 months of age
Cytokine profiles
time frame: 0-13 months of age
Antibody titres following immunisation against diphtheria, tetanus, pertussis, pneumococcus, hemophilus
time frame: 0-13 months of age
Common cold
time frame: 0-13 months of age
Pneumonia
time frame: 0-13 months of age
Febrile episodes
time frame: 0-13 months of age
Episodes with diarrhoea and vomiting
time frame: 0-13 months of age
Acute otitis media
time frame: 0-13 months of age
Febrile convulsions
time frame: 0-13 months of age

Eligibility Criteria

Male or female participants up to 7 days old.

Inclusion Criteria: - All parents planning to give birth at Rigshospitalet, Hvidovre Hospital and Kolding Hospital will receive at letter during 2nd/3rd trimester of pregnancy with information on the study and be offered inclusion in the study. Exclusion Criteria: - Infants born before gestational age 32 weeks and/or birth weight < 1000g, infants with known congenital disease, anomaly or malformation, immune deficiency and HIV, will be excluded. Non‐Danish speaking parents will be excluded.

Additional Information

Official title Bacille Calmette Guérin Immunisation at Birth and Childhood Morbidity in Danish Children. A Prospective, Randomised, Clinical Trial.
Principal investigator Lone G Stensballe, MD, PhD
Trial information was received from ClinicalTrials.gov and was last updated in May 2015.
Information provided to ClinicalTrials.gov by Rigshospitalet, Denmark.