Trial record 9 of 40 for:    Febrile Seizures

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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Hvidovre University Hospital
Kolding Sygehus
Danish National Research Foundation
Research Center for Vitamins and Vaccines (CVIVA)
Information provided by (Responsible Party):
Lone Graff Stensballe, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01694108
First received: September 22, 2012
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

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.

Condition Intervention Phase
Prospective
Single-blind
Clinical
Trial
Intervention
Biological: BCG-vaccine (SSI)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Bacille Calmette Guérin Immunisation at Birth and Childhood Morbidity in Danish Children. A Prospective, Randomised, Clinical Trial.

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Hospitalisations [ Time Frame: 0-2 years of age ] [ Designated as safety issue: No ]
    To test that infants who get the BCG vaccine at birth experience 20% fewer hospitalisations in early childhood than non-BCG-immunised infants.


Secondary Outcome Measures:
  • Antibiotics [ Time Frame: 0-2 years of age ] [ Designated as safety issue: No ]
    To test that infants who get the BCG vaccine at birth are prescribed less antibiotics during early childhood than non-BCG-immunised infants.

  • Eczema [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    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.

  • Specific IgE [ Time Frame: 13 months of age ] [ Designated as safety issue: No ]
    To test that infants who receive the BCG at birth respond in specific IgE.

  • Weight [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    To test that infants who get the BCG vaccine at birth respond in weight.

  • Psychomotor development in premature infants [ Time Frame: 0-13 months of age ] [ Designated as safety issue: Yes ]
    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.

  • Vaccination coverage [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    To test that infants who get the BCG vaccine at birth has unaffected coverage with the subsequent vaccinations in the Child Vaccination Programme.

  • Premature infants [ Time Frame: 0-2 years of age ] [ Designated as safety issue: No ]
    To test the outcome measures specifically in the strata of premature and low-birth-weight Danish infants.

  • Asthma [ Time Frame: 0-13 months ] [ Designated as safety issue: No ]
    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.

  • Food allergy [ Time Frame: 0-13 months ] [ Designated as safety issue: No ]
    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.

  • Length [ Time Frame: 0-13months ] [ Designated as safety issue: No ]
    To test that infants who get the BCG vaccine at birth respond in length.

  • Head circumference [ Time Frame: 0-13months ] [ Designated as safety issue: No ]
    To test that infants who get the BCG vaccine at birth respond in head circumference.

  • Thymic gland size [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    To test that infants who receive the BCG at birth respond in thymic gland size.

  • Leucocyte count and differentiation [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    To test that infants who receive the BCG at birth respond in leucocyte count and differentiation.

  • Monocyte memory [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    To test that infants who receive the BCG at birth respond in monocyte memory.

  • Cytokine profiles [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    To test that infants who receive the BCG at birth respond in cytokine profiles.

  • Antibody titres following immunisation against diphtheria, tetanus, pertussis, pneumococcus, hemophilus [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    To test that infants who receive the BCG at birth respond in antibody titres following immunisation against diphtheria, tetanus, pertussis, pneumococcus, and haemophilus.

  • Common cold [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    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.

  • Pneumonia [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    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.

  • Febrile episodes [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    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.

  • Episodes with diarrhoea and vomiting [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    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.

  • Acute otitis media [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    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.

  • Febrile convulsions [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Qualitative research [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    1. From qualitative research in focus groups: parents' attitudes and opinions about letting their child BCG vaccinate.
    2. "Decisional conflict scale" will be used to score and analyse decisional conflicts for both participants and non-participants.
    3. 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.
    4. "Decisional conflict scale" to score and analyse the parents decisional conflicts for letting the child vaccinate with di-te-ki-pol/Hib.

  • Communication and information [ Time Frame: 0-13 months of age ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 4300
Study Start Date: September 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BCG-vaccine (SSI)

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.

Biological: BCG-vaccine (SSI)
No Intervention: No Intervention
Control children will be treated as usual, since no suitable placebo exists.

  Eligibility

Ages Eligible for Study:   up to 7 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01694108

Locations
Denmark
Rigshospitalet
Copenhagen, Copenhagen Ø, Denmark, 2100
Hvidovre Hospital
Copenhagen, Denmark, 2650
Kolding Sygehus
Kolding, Denmark, 6000
Sponsors and Collaborators
Lone Graff Stensballe
Hvidovre University Hospital
Kolding Sygehus
Danish National Research Foundation
Research Center for Vitamins and Vaccines (CVIVA)
Investigators
Principal Investigator: Lone G Stensballe, MD, PhD Rigshospitalet. The Danish National Hospital in Denmark.
  More Information

Additional Information:
No publications provided

Responsible Party: Lone Graff Stensballe, MD, PhD, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01694108     History of Changes
Other Study ID Numbers: EudraCT2010-021979-85
Study First Received: September 22, 2012
Last Updated: February 18, 2014
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:

Additional relevant MeSH terms:
BCG Vaccine
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014