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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02444611




Registration number
NCT02444611
Ethics application status
Date submitted
6/04/2015
Date registered
14/05/2015
Date last updated
31/08/2017

Titles & IDs
Public title
A Trial Investigating the Influence of BCG and Hepatitis B Immunisation at Birth on Neonatal Immune Responses: The Early Life Vaccines and Immunity Study
Scientific title
A Randomised, Controlled Trial Investigating the Influence of BCG (Bacillus Calmette-Guérin) and Hepatitis B Immunisation at Birth on Neonatal Immune Responses
Secondary ID [1] 0 0
VAC/01 ELVIS
Universal Trial Number (UTN)
Trial acronym
ELVIS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Innate Immune Response 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BCG Vaccine
Treatment: Drugs - Hepatitis B Vaccine

Active Comparator: Group 1 - BCG vaccine, 0,05ml intradermally at birth

Active Comparator: Group 2 - BCG vaccine, 0,05ml intradermally at birth Hepatitis B vaccine, 5 micrograms, intramuscularly at birth

Active Comparator: Group 3 - Hepatitis B vaccine, 5 micrograms, intramuscularly at birth

No Intervention: Group 4 - No birth vaccines


Treatment: Drugs: BCG Vaccine
intradermal vaccination

Treatment: Drugs: Hepatitis B Vaccine
intramuscular vaccination

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cytokine concentrations (pg/ml) in response to in-vitro stimulation with a range of antigens - Four hours after blood samples are collected, they will be stimulated with different concentrations of infective antigens for 20hrs. (eg killed S.aureus, S. pneumoniae, E. Coli, Haemophilus Influenza B, Group B streptococcus, C. albicans), BCG, Hepatitis B sAg). Cytokine expression will be analysed in supernatants by Luminex -based multiplex assays.
The cytokines that will be measured:
Interleukin-1 beta, Interleukin-1ra, Interleukin-6, Interleukin-8, Macrophage/Monocyte Chemoattractant Protein-1(MCP-1), Macrophage Inflammatory Protein (MIP) -1 alpha, MIP-1 beta, Interferon(IFN) gamma, Interleukin-10, Macrophage migration inhibitory factor (MIF), Monokine induced by interferon (MIG), Tumour necrosis factor (TNF) alpha
Timepoint [1] 0 0
7 (+-4) days post randomisation

Eligibility
Key inclusion criteria
- English speaking parent

- Planned travel to a TB (Tuberculosis) endemic country within the infant's first 5
years of life

- An informed consent form must be signed and dated by the infant's mother 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

- The infant's mother has screened negative for Hepatitis B during this pregnancy

- There is no known household contact infected with Hepatitis B

- Born no earlier than eight weeks before estimated date of delivery

- Birth weight >1500g

- Delivered vaginally

- Singleton pregnancy
Minimum age
No limit
Maximum age
3 Days
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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 (biological Disease- Modifying Anti-Rheumatic
drugs) (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

Also excluded are infants with:

1. A mother who is immunosuppressed;

2. A mother who has received Intravenous immunoglobulins during her pregnancy

3. A family history of immunodeficiency;

4. Consanguineous parents.

5. Mother who is having a planned Caesarean Section

6. A home address more than 40 minutes drive from the Mercy hospital for Women and are
unwilling to return to hospital for infant blood sampling

Study design
Purpose of the study
Basic Science
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Mercy Hospital for Women - Heidelberg
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Royal Children's Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Mercy Hospital for Women, Australia
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Neonatal morbidity and mortality from infectious diseases is of global concern. Childhood
disease-specific immunisation is irrefutably linked to the decline in deaths from these
targeted infections over the last century. However, neonatal immunisation is limited, in
part, by the impaired adaptive immune function in this age group.

There is now an expanding body of evidence for heterologous ('non-specific') effects of
various vaccines used in childhood. This refers to the immunomodulatory capabilities of
vaccines to influence immune outcomes beyond the vaccine's specific targeted disease. The
underlying immunological mechanisms responsible for these effects are incompletely
understood, but evidence is mounting that the innate immune system is central to these
observed effects.

This study is a randomised controlled trial designed to determine the influence of two
commonly administered neonatal immunisations, BCG and Hepatitis B vaccine, given at birth, on
the neonatal immune responses to non-specific antigens.

The investigators will recruit 200 newborns at the Mercy Hospital for Women in Melbourne,
Australia over a 1-year period. These babies will be allocated randomly to one of 4 groups,
receiving these 2 vaccines in different combinations, at 2 set time points. (at birth and 1
week post randomisation) A blood sample will be taken at 1-week post randomisation for in
vitro immunological analyses.

This study will improve current understanding of the influence of vaccines on neonatal
immunity and will help develop strategies exploiting beneficial heterologous ('non-specific')
effects to improve protection against infection in the very young.
Trial website
https://clinicaltrials.gov/show/NCT02444611
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nigel Curtis, MBBS,PHD
Address 0 0
Royal Children's Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications