Comparing Morbidity and Mortality Effects of Two Different Strains of BCG

NCT03400878 | Completed Phase 4 DMC

• 1 other identifier: BCGSTRAIN II
• Study Type: interventional
• Target: 17,505
• Locations: 1 country
• Sites: 2

Brief Summary

Background: Investigators at Bandim Health Project (BHP, www.bandim.org) in Guinea-Bissau have shown in several randomized trials that the Bacille-Calmette-Guérin (BCG) vaccine against tuberculosis (TB) is associated with reduced mortality in the first months of life. BCG is a live attenuated vaccine, which means that it consists of active tuberculosis bacteria that are not capable of infecting a human with TB. BCG has been grown and maintained at many different laboratories all over the world using slightly different laboratory techniques. Due to the accumulation of genetic mutations in the different BCG strains, many variants of the vaccine exists today. These have different properties when it comes to immune response, side effects, protection against TB and scar formation. The BCG scar status after vaccination is a good marker for the non-specific effects of the vaccine; among BCG-vaccinated infants, those with a BCG scar have improved survival. The investigators hypothesize that the different types of BCG vary in terms of the strength of the non-specific effects and thus the impact on overall morbidity and mortality. In the trial, the investigators will compare the two most widely used BCG strains in the world, BCG-Russia and BCG-Japan, with respect to their non-specific effects on morbidity and mortality. As an addition, the investigators will study the effect of maternal BCG vaccination on the subsequent effect of BCG-vaccination in the offspring, since there are indications that the maternal BCG scar status primes for a stronger non-specific response in the offspring.

Conditions

Heterologous Immunity; Infant Morbidity; Infant Mortality; Trained Immunity; Vaccine Reaction; Vaccine Adverse Reaction

Outcome Measures

Primary Outcomes (1)

• Hospital admission at National Hospital Simão Mendes Pediatric Ward

  Number of participants admitted to the Pediatric Ward of National Hospital Simão Mendes within up to 6 weeks (42 days) of age. BHP documents all admissions at the ward.

  6 weeks

Secondary Outcomes (11)

• Hospital admission at National Hospital Simão Mendes Pediatric Ward

  6 months

• In-hospital case-fatality rate at National Hospital Simão Mendes Pediatric Ward

  6 weeks

• In-hospital case-fatality rate at Pediatric Ward

  6 months

• Mortality

  6 weeks

• Mortality

  6 months

Study Arms (2)

BCG-JAPAN

ACTIVE COMPARATOR

Infants randomised to receive BCG-JAPAN at discharge from the Maternity Ward will receive one 0.05 ml dose of Mycobacterium bovis BCG live attenuated BCG-JAPAN vaccine (Japan BCG Laboratory, Tokyo, Japan) by intradermal injection in the left deltoid region.

Biological: BCG-Japan

BCG-RUSSIA

ACTIVE COMPARATOR

BCG-RUSSIA Infants randomised 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 (Serum Institute of India, Pune, India) by intradermal injection in the left deltoid region.

Biological: BCG-Russia

Interventions

BCG-Japan BIOLOGICAL

One dose of 0.05 ml BCG-Japan vaccine applied to the left deltoid region.

BCG-JAPAN

BCG-Russia BIOLOGICAL

One dose of 0.05 ml BCG-Russia vaccine applied to the left deltoid region.

BCG-RUSSIA

Eligibility Criteria

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

You may qualify if:

• Newborn, unvaccinated infants identified at the maternity ward and ready to be discharged

You may not qualify if:

• Infants above 6 weeks (\>42 days) of age; Infants with gross malformation; Infants that are acutely ill

Sponsors & Collaborators

• Bandim Health Project: lead
• Research Center for Vitamins and Vaccines: collaborator

Study Sites (2)

Bandim Health Project, Apartado 861

Bissau, Guinea-Bissau

Location

Bandim Health Project

Bissau, Guinea-Bissau

Location

Related Publications (1)

• Schaltz-Buchholzer F, Nielsen S, Sorensen MK, Stjernholm EB, Fabricius RA, Umbasse P, Monteiro I, Ca EJC, Aaby P, Benn CS. Effects of Neonatal BCG-Japan Versus BCG-Russia Vaccination on Overall Mortality and Morbidity: Randomized Controlled Trial From Guinea-Bissau (BCGSTRAIN II). Open Forum Infect Dis. 2024 Feb 1;11(3):ofae057. doi: 10.1093/ofid/ofae057. eCollection 2024 Mar.

  PMID: 38500576 DERIVED

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised trial of 15,600 infants 1:1 to BCG-Japan or BCG-Russia

Study Record Dates

• First Submitted: November 28, 2017
• First Posted: January 17, 2018
• Study Start: October 14, 2017
• Primary Completion: June 1, 2020
• Study Completion: October 1, 2020
• Last Updated: December 16, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: When follow-up has been completed and the dataset have been closed (e.g. by november or december 2020)
• Access Criteria: Non-identifiable individual data can be shared on the basis of a data sharing proposal sent to cbenn@health.sdu.dk

Locations

GU (2)