Bacille Calmette Guérin Immunisation at Birth and Childhood Morbidity in Danish Children.

Intervention Clinical Trial

Official title:

Bacille Calmette Guérin Immunisation at Birth and Childhood Morbidity in Danish Children. A Prospective, Randomised, Clinical Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01694108
• Other study ID #: EudraCT2010-021979-85
• Status: Completed
• Phase: Phase 4
• First received: September 22, 2012
• Last updated: December 3, 2015
• Start date: September 2012
• Est. completion date: January 2015

Study information

• Verified date: December 2015
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: The Committee on Health Research Ethics, Copenhagen, Denmark:The Danish Data Protection Agency, Copenhagen, Denmark:The Good Clinical Practise Unit in Copenhagen, Denmark:The Good Clinical Practise Unit in South Denmark, Denmark:The Danish Health and Medicines Authority, Copenhagen, Denmark:EuDraCT, European Union, Europe:
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4262
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 7 Days

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Clinical
• Intervention
• Prospective
• Single-blind
• Trial

Intervention

Biological:
• BCG-vaccine (SSI)

Locations

Country	Name	City	State
Denmark	Hvidovre Hospital	Copenhagen
Denmark	Rigshospitalet	Copenhagen	Copenhagen Ø
Denmark	Kolding Sygehus	Kolding

Sponsors (5)

Lead Sponsor	Collaborator
Lone Graff Stensballe	Danish National Research Foundation, Hvidovre University Hospital, Kolding Sygehus, Research Center for Vitamins and Vaccines (CVIVA)

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Qualitative Research	From qualitative research in focus groups: parents' attitudes and opinions about letting their child BCG vaccinate.; "Decisional conflict scale" will be used to score and analyse decisional conflicts for both participants and non-participants.; Telephone interview at 3 months of age: The parents' experiences with information given, the vaccination and side effects. From focus group interviews develop and qualify information given to parents before BCG vaccination.; "Decisional conflict scale" to score and analyse the parents decisional conflicts for letting the child vaccinate with di-te-ki-pol/Hib.	0-13 months of age	No
Other	Communication and Information	To test that the use of telephone and internet will be highly acceptable in this young population. To test scores of information, understanding, competence, and voluntariness.	0-13 months of age	No
Primary	All-cause Hospitalisations	To test that infants who get the BCG vaccine at birth experience 20% fewer hospitalisations in early childhood than non-BCG-immunised infants.	0-15 months of age	No
Secondary	Antibiotics	To test that infants who get the BCG vaccine at birth are prescribed less antibiotics during early childhood than non-BCG-immunised infants.	0-2 years of age	No
Secondary	Eczema	To test that Danish infants who get the BCG vaccine at birth develop less eczema at 3 and 12 months of age: self-reported, diagnosed by a physician, or found at clinical examination; and are prescribed less anti-eczema medication during early childhood than non-BCG-immunised infants.	0-13 months of age	No
Secondary	Specific IgE	To test that infants who receive the BCG at birth respond in specific IgE.	13 months of age	No
Secondary	Weight	To test that infants who get the BCG vaccine at birth respond in weight.	0-13 months of age	No
Secondary	Psychomotor Development in Premature Infants	To test 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.	0-13 months of age	Yes
Secondary	Vaccination Coverage	To test that infants who get the BCG vaccine at birth has unaffected coverage with the subsequent vaccinations in the Child Vaccination Programme.	0-13 months of age	No
Secondary	Premature Infants	To test the outcome measures specifically in the strata of premature and low-birth-weight Danish infants.	0-2 years of age	No
Secondary	Asthma	To test that Danish infants who get the BCG vaccine at birth develop less asthma at 3 and 12 months of age: self-reported, diagnosed by a physician, or found at clinical examination; and are prescribed less anti-asthma medication during early childhood than non-BCG-immunised infants.	0-13 months	No
Secondary	Food Allergy	To test that Danish infants who get the BCG vaccine at birth develop less 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-allergy medication during early childhood than non-BCG-immunised infants.	0-13 months	No
Secondary	Length	To test that infants who get the BCG vaccine at birth respond in length.	0-13months	No
Secondary	Head Circumference	To test that infants who get the BCG vaccine at birth respond in head circumference.	0-13months	No
Secondary	Thymic Gland Size	To test that infants who receive the BCG at birth respond in thymic gland size.	0-13 months of age	No
Secondary	Leucocyte Count and Differentiation	To test that infants who receive the BCG at birth respond in leucocyte count and differentiation.	0-13 months of age	No
Secondary	Monocyte Memory	To test that infants who receive the BCG at birth respond in monocyte memory.	0-13 months of age	No
Secondary	Cytokine Profiles	To test that infants who receive the BCG at birth respond in cytokine profiles.	0-13 months of age	No
Secondary	Antibody Titres Following Immunisation Against Diphtheria, Tetanus, Pertussis, Pneumococcus, Hemophilus	To test that infants who receive the BCG at birth respond in antibody titres following immunisation against diphtheria, tetanus, pertussis, pneumococcus, and haemophilus.	0-13 months of age	No
Secondary	Common Cold	To test that Danish infants who get the BCG vaccine at birth develop less common cold at 3 and 13 months of age than non-BCG-immunised infants.	0-13 months of age	No
Secondary	Pneumonia	To test that Danish infants who get the BCG vaccine at birth develop less pneumonia at 3 and 13 months of age than non-BCG-immunised infants.	0-13 months of age	No
Secondary	Febrile Episodes	To test that Danish infants who get the BCG vaccine at birth develop less febrile episodes at 3 and 13 months of age than non-BCG-immunised infants.	0-13 months of age	No
Secondary	Episodes With Diarrhoea and Vomiting	To test that Danish infants who get the BCG vaccine at birth develop less episodes with diarrhoea and vomiting at 3 and 13 months of age than non-BCG-immunised infants.	0-13 months of age	No
Secondary	Acute Otitis Media	To test that Danish infants who get the BCG vaccine at birth develop less acute otitis media at 3 and 13 months of age than non-BCG-immunised infants.	0-13 months of age	No
Secondary	Febrile Convulsions	To test that Danish infants who get the BCG vaccine at birth develop less febrile convulsions at 3 and 13 months of age than non-BCG-immunised infants.	0-13 months of age	No

External Links

•   Study home page