Trial of Two Strains of BCG (BCGSTRAIN)

December 13, 2020 updated by: Bandim Health Project

Evaluating the Effect of Different BCG Strains on Early Life Hospital Admissions in Guinea-Bissau: A Randomised Trial

The investigators aim to conduct a randomised controlled trial comparing two Bacille Calmette-Guérin (BCG) strains currently used in Guinea-Bissau, the Danish and the Russian, in terms of prevention of neonatal and early life morbidity and mortality, immune responses and adverse events related to BCG vaccination. The primary outcome will be hospital admissions within 6 weeks of age.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

BACKGROUND At the Bandim Health Project (www.bandim.org) in Guinea-Bissau, we observed that Bacille Calmette-Guérin (BCG) vaccination at birth is associated with survival benefits which cannot be explained by prevention of tuberculosis (TB), which is rare during the first year of life. There is mounting evidence that the beneficial effects of BCG on neonatal mortality stems from non-specific beneficial immune training, also termed heterologous immunity. This way, BCG immunisation possibly confers enhanced protection against a broad range of severe infections such as pneumonia and septicemia.

In addition, observational studies from Guinea-Bissau suggest that BCG-vaccinated children who produced a scar upon immunisation have significantly better survival than BCG-vaccinated children who did not produce a scar. The pattern is the same with regard to PPD (tuberculin) skin test. While correct BCG-vaccination technique is undoubtedly important for scarring, several studies have shown that the strain of BCG might be important as well.

Globally, BCG coverage exceeds 90%, making BCG the most widely used vaccine in the world. According to UNICEF, the annual demand for the BCG vaccine was 130 million doses in 2013. Several different vaccine strains are being used, yet few studies have compared the different strains. However, several animal and human studies have shown that these genetically diverse vaccine strains induce different protective efficacy against TB, risk of adverse events and susceptibility to anti-TB drugs. Recently, a large observational study based in Uganda showed that there were significant differences between BCG strains concerning the response to specific mycobacteria and non-specific immune responses. In particular, BCG-Denmark was associated with a much higher rate of scarring (93%) than BCG-Russia (52%), but also a higher rate of adverse events in terms of ulcers and abscesses (1.8% versus 0.3%).

OBJECTIVE We aim to compare the effect of two strains of BCG (BCG-Denmark, BCG-Russia) provided at birth to children born at the National Hospital Simão Mendes (HNSM) on subsequent hospitalisations. Furthermore, mortality in the first 6 weeks and adverse events at 2 and 6 months of age will be reported for all children, and BCG scar frequency (2 and 6 months) and PPD response (6 months) will be reported for a proportion of the infants.

METHODS The study will be conducted by the Bandim Health Project (BHP). The BHP maintains a health and demographic surveillance system (HDSS) in 6 districts of the capital in Guinea-Bissau covering approximately 102,000 inhabitants. All houses in the HDSS are visited monthly and all pregnancies and births are registered.

Study participants will be enrolled at the National Hospital and followed up through the HDSS and by telephone interviews as well as through hospital records. The study will be individually randomised, with 1:1 randomisation between the two strains (BCG-Denmark, BCG-Russia). During a two year inclusion period, we expect to be able to include at least 12,000 children, i.e. 6,000 in each BCG strain group. Of these, around 25% will reside within the HDSS.

Study Type

Interventional

Enrollment (Actual)

12006

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Guinea-Bissau
      • Bissau, Guinea-Bissau
        • Bandim Health Project, Apartado 861

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

Newborn infants at the HNSM maternity ward.

Exclusion Criteria:

Infants included in another randomized trial of BCG. Infants with a severe congenital abnormality.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: BCG-DENMARK

Infants randomised to receive BCG-DENMARK at dismissal from the Maternity Ward will receive one 0.05 ml dose of Mycobacterium bovis BCG live attenuated vaccine BCG-Denmark 1331 (Statens Serum Institute) 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.

NOTE: By 1st of July 2016, infants in this arm has received BCG-Japan due to a worldwide shortage of BCG-Denmark because of a halt in production of this vaccine at the Statens Serum Institut in Copenhagen.
Biological: BCG-Denmark 1331 (Statens Serum Institute)
See above
ACTIVE_COMPARATOR: BCG-RUSSIA
Infants randomised to receive BCG-RUSSIA at dismissal 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-I (Serum Institute of India)
See above

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Hospital admission
Time Frame: 6 weeks after birth
6 weeks after birth

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: 6 weeks
Reported exclusively for a subgroup of infants with regular house visits
6 weeks
BCG scar frequency
Time Frame: 6 months
Reported exclusively for a subgroup of infants with regular house visits
6 months
PPD (tuberculin response)
Time Frame: 6 months
Reported exclusively for a subgroup of infants with regular house visits
6 months
Adverse events (abscesses/ulcers)
Time Frame: 6 months
Adverse events to the vaccines will be evaluated for a subgroup of infants with regular house visits
6 months
Hospital admission during neonatal period
Time Frame: 4 weeks
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bandim Health Project

Collaborators

Statens Serum Institut

Investigators

  • Principal Investigator: Peter Aaby, Prof., Bandim Health Project

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 8, 2014

Primary Completion (ACTUAL)

November 24, 2017

Study Completion (ACTUAL)

May 1, 2018

Study Registration Dates

First Submitted

April 20, 2015

First Submitted That Met QC Criteria

May 14, 2015

First Posted (ESTIMATE)

May 19, 2015

Study Record Updates

Last Update Posted (ACTUAL)

December 16, 2020

Last Update Submitted That Met QC Criteria

December 13, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • BCGSTRAIN

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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