Trial to Compare Two Strains of BCG

NCT04383925 | Completed Phase 4

• 3 other identifiers: BCGSTRAIN III071/CNES/INASA/20202002944
• Study Type: interventional
• Target: 16,390
• Locations: 1 country
• Sites: 1

Brief Summary

The trial will be a two-year outcome assessor-blinded RCT at the maternity ward of hospital Simão Mendes (HNSM) in urban Bissau, Guinea-Bissau to compare BCG-Japan versus BCG-Russia 1:1 in 15,000 infants with respect to mortality, morbidity and case-fatality rate during hospital admission. The trial will also examine the association between BCG strains and BCG skin reaction characteristics by six weeks (data collected by telephone) and at two and six months (data collected at home-visits to a subgroup of the cohort). As a secondary aim, this large study will be used to further evaluate the role of maternal BCG immune priming for overall health, since there are indications that maternal BCG scarring enhances the non-specific effects of BCG.

Conditions

Death, Infant; Morbidity;Infant

Keywords

BCG vaccination; Non-specific effects of BCG; Heterologous effects; Maternal immune priming

Outcome Measures

Primary Outcomes (1)

• Rate of all-cause mortality overall and stratified by maternal BCG scar status and sex

  Data on mortality is collected from all available information sources (admission at HNSM, telephone follow-up, HDSS data)

  Six weeks of age

Secondary Outcomes (7)

• Rate of hospital admissions overall and stratified by maternal BCG scar status and sex

  Six weeks and six months of age

• In-hospital case-fatality risk ratio overall and stratified by maternal BCG scar status and sex

  Six weeks and six months of age

• Prevalence of BCG skin reactions

  Six weeks and six months of age

• Prevalence of BCG skin reactions

  Six weeks and six months of age

• Prevalence of different BCG skin reaction types

  Two and six months of age

Study Arms (2)

BCG-Japan

EXPERIMENTAL

Infants randomized to receive BCG-Japan at discharge from the Maternity Ward will receive one 0.05 ml dose of Mycobacterium bovis BCG live attenuated vaccine BCG-Japan (Tokyo BCG Laboratory) by intradermal injection in the left deltoid region. Dependent on national supply, infants will receive oral polio vaccine (OPV) at the time of BCG vaccination.

Biological: BCG-Japan

BCG-Russia

ACTIVE COMPARATOR

Infants randomized to receive BCG-Russia at discharge from the Maternity Ward will receive one 0.05 ml dose Mycobacterium bovis BCG live attenuated vaccine BCG-Russia-I (Serum Institute of India) by intradermal injection in the left deltoid region. Dependent on national supply, infants will receive oral polio vaccine (OPV) at the time of BCG-vaccination.

Biological: BCG-Russia

Interventions

BCG-Japan BIOLOGICAL

Infant (\<1 year) 0.05 ml dose of resuspended BCG-Japan (Tokyo strain 172, Japan BCG Laboratory, 1-5-21 Otsuka, Bunkyo-ku, Tokyo, 112-0012 Japan).

Also known as: Tokyo strain 172

BCG-Japan

BCG-Russia BIOLOGICAL

Infant (\<1 year) 0.05 ml dose of resuspended BCG-Russia (Serum Institute of India)

BCG-Russia

Eligibility Criteria

• Age: 0 Days - 42 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Healthy infants present at the HNSM maternity ward on the day of discharge or procuring vaccination at the ward.

You may not qualify if:

• Infants older than 6 weeks (\>42 days) of age
• Infants that have already received either BCG or oral polio vaccine (OPV)
• Infants that are moribund due to gross malformation or acute illness (about to die or be transferred to the pediatric ward according to the local health physician assessment; the latter children may be recruited when they are discharged from the pediatric ward or the neonatal intensive care unit).

Sponsors & Collaborators

• Bandim Health Project: lead
• University of Southern Denmark: collaborator

Study Sites (1)

Bandim Health Project

Bissau, Guinea-Bissau

Location

Related Publications (37)

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Related Links

• WHO data regarding child mortality.
• The BCGSTRAIN II trial from which the results have not yet been published (follow-up is still pending and will be finished by october 2020).
• Description of the verbal autopsy instrument which will be used for HDSS infants included in the trial.
• Evidence based recommendations on non-specific effects of BCG, DTP-containing and measles-containing vaccines on mortality in children under 5 years of age. Background paper for SAGE discussions

MeSH Terms

Conditions

Infant Death

Condition Hierarchy (Ancestors)

Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Peter Aaby, Professor

  Bandim Health Project

  PRINCIPAL INVESTIGATOR

• Christine Stabell Benn, Professor

  Bandim Health Project, University of Southern Denmark

  STUDY CHAIR

• Frederik Schaltz-Buchholzer, MD

  Bandim Health Project, University of Southern Denmark

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Following informed consent, the mother selects, from a stack of envelopes, a closed envelope that contains a sealed randomization lot indicating allocation to either BCG-Japan or BCG-Russia. The mother, inclusion assistant and vaccinator will thus not be blinded to the intervention allocation. All assistants assessing outcomes during the follow-up procedures outlined and providers of care will be blinded to the randomization allocation.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Outcome assessor-blinded RCT

Study Record Dates

• First Submitted: May 4, 2020
• First Posted: May 12, 2020
• Study Start: May 4, 2020
• Primary Completion: October 30, 2022
• Study Completion: December 1, 2022
• Last Updated: January 22, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: One year after follow-up procedures have been completed.
• Access Criteria: The trial steering committee can be approached for data sharing at cbenn@health.sdu.dk

Locations

GU (1)