NCT02447536

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12,006

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Dec 2014

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 8, 2014

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

April 20, 2015

Completed
29 days until next milestone

First Posted

Study publicly available on registry

May 19, 2015

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 24, 2017

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2018

Completed
Last Updated

December 16, 2020

Status Verified

December 1, 2020

Enrollment Period

3 years

First QC Date

April 20, 2015

Last Update Submit

December 13, 2020

Conditions

MorbidityBacille Calmette-Guérin

Keywords

ImmunizationMorbidityMortalityBCG

Outcome Measures

Primary Outcomes (1)

  • Hospital admission

    6 weeks after birth

Secondary Outcomes (5)

  • Mortality

    6 weeks

  • BCG scar frequency

    6 months

  • PPD (tuberculin response)

    6 months

  • Adverse events (abscesses/ulcers)

    6 months

  • Hospital admission during neonatal period

    4 weeks

Study Arms (2)

BCG-DENMARK

ACTIVE COMPARATOR

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)

BCG-RUSSIA

ACTIVE COMPARATOR

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)

Interventions

BCG-Denmark 1331 (Statens Serum Institute)BIOLOGICAL

See above

BCG-DENMARK
BCG-Russia-I (Serum Institute of India)BIOLOGICAL

See above

BCG-RUSSIA

Eligibility Criteria

Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Newborn infants at the HNSM maternity ward.

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Bandim Health Project, Apartado 861

Bissau, Guinea-Bissau

Location

Related Publications (18)

  • Wardlaw T, You D, Newby H, Anthony D, Chopra M. Child survival: a message of hope but a call for renewed commitment in UNICEF report. Reprod Health. 2013 Dec 11;10:64. doi: 10.1186/1742-4755-10-64.

    PMID: 24325885BACKGROUND

  • Lawn JE, Cousens S, Zupan J; Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: when? Where? Why? Lancet. 2005 Mar 5-11;365(9462):891-900. doi: 10.1016/S0140-6736(05)71048-5.

    PMID: 15752534BACKGROUND

  • Penfold S, Willey BA, Schellenberg J. Newborn care behaviours and neonatal survival: evidence from sub-Saharan Africa. Trop Med Int Health. 2013 Nov;18(11):1294-316. doi: 10.1111/tmi.12193. Epub 2013 Sep 24.

    PMID: 24112377BACKGROUND

  • Aaby P, Roth A, Ravn H, Napirna BM, Rodrigues A, Lisse IM, Stensballe L, Diness BR, Lausch KR, Lund N, Biering-Sorensen S, Whittle H, Benn CS. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J Infect Dis. 2011 Jul 15;204(2):245-52. doi: 10.1093/infdis/jir240.

    PMID: 21673035BACKGROUND

  • Biering-Sorensen S, Aaby P, Napirna BM, Roth A, Ravn H, Rodrigues A, Whittle H, Benn CS. Small randomized trial among low-birth-weight children receiving bacillus Calmette-Guerin vaccination at first health center contact. Pediatr Infect Dis J. 2012 Mar;31(3):306-8. doi: 10.1097/INF.0b013e3182458289.

    PMID: 22189537BACKGROUND

  • Roth A, Gustafson P, Nhaga A, Djana Q, Poulsen A, Garly ML, Jensen H, Sodemann M, Rodriques A, Aaby P. BCG vaccination scar associated with better childhood survival in Guinea-Bissau. Int J Epidemiol. 2005 Jun;34(3):540-7. doi: 10.1093/ije/dyh392. Epub 2005 Jan 19.

    PMID: 15659474BACKGROUND

  • Garly ML, Martins CL, Bale C, Balde MA, Hedegaard KL, Gustafson P, Lisse IM, Whittle HC, Aaby P. BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG? Vaccine. 2003 Jun 20;21(21-22):2782-90. doi: 10.1016/s0264-410x(03)00181-6.

    PMID: 12798618BACKGROUND

  • Roth A, Sodemann M, Jensen H, Poulsen A, Gustafson P, Weise C, Gomes J, Djana Q, Jakobsen M, Garly ML, Rodrigues A, Aaby P. Tuberculin reaction, BCG scar, and lower female mortality. Epidemiology. 2006 Sep;17(5):562-8. doi: 10.1097/01.ede.0000231546.14749.ab.

    PMID: 16878042BACKGROUND

  • Behr MA. BCG--different strains, different vaccines? Lancet Infect Dis. 2002 Feb;2(2):86-92. doi: 10.1016/s1473-3099(02)00182-2.

    PMID: 11901655BACKGROUND

  • Ritz N, Curtis N. Mapping the global use of different BCG vaccine strains. Tuberculosis (Edinb). 2009 Jul;89(4):248-51. doi: 10.1016/j.tube.2009.03.002. Epub 2009 Jun 18.

    PMID: 19540166BACKGROUND

  • Behr MA. Correlation between BCG genomics and protective efficacy. Scand J Infect Dis. 2001;33(4):249-52. doi: 10.1080/003655401300077180.

    PMID: 11345214BACKGROUND

  • Ritz N, Hanekom WA, Robins-Browne R, Britton WJ, Curtis N. Influence of BCG vaccine strain on the immune response and protection against tuberculosis. FEMS Microbiol Rev. 2008 Aug;32(5):821-41. doi: 10.1111/j.1574-6976.2008.00118.x. Epub 2008 Jul 9.

    PMID: 18616602BACKGROUND

  • Anderson EJ, Webb EL, Mawa PA, Kizza M, Lyadda N, Nampijja M, Elliott AM. The influence of BCG vaccine strain on mycobacteria-specific and non-specific immune responses in a prospective cohort of infants in Uganda. Vaccine. 2012 Mar 9;30(12):2083-9. doi: 10.1016/j.vaccine.2012.01.053. Epub 2012 Jan 31.

    PMID: 22300718BACKGROUND

  • Biai S, Rodrigues A, Nielsen J, Sodemann M, Aaby P. Vaccination status and sequence of vaccinations as risk factors for hospitalisation among outpatients in a high mortality country. Vaccine. 2011 May 9;29(20):3662-9. doi: 10.1016/j.vaccine.2011.03.016. Epub 2011 Apr 6.

    PMID: 21440640BACKGROUND

  • Aaby P, Whittle H, Benn CS. Vaccine programmes must consider their effect on general resistance. BMJ. 2012 Jun 14;344:e3769. doi: 10.1136/bmj.e3769. No abstract available.

    PMID: 22700785BACKGROUND

  • Schaltz-Buchholzer F, Bjerregaard-Andersen M, Oland CB, Golding C, Stjernholm EB, Monteiro I, Aaby P, Benn CS. Early Vaccination With Bacille Calmette-Guerin-Denmark or BCG-Japan Versus BCG-Russia to Healthy Newborns in Guinea-Bissau: A Randomized Controlled Trial. Clin Infect Dis. 2020 Nov 5;71(8):1883-1893. doi: 10.1093/cid/ciz1080.

    PMID: 31677386RESULT

  • Schaltz-Buchholzer F, Bjerregard Oland C, Berendsen M, Bjerregaard-Andersen M, Stjernholm EB, Golding CN, Monteiro I, Aaby P, Benn CS. Maternal BCG primes for enhanced health benefits in the newborn. J Infect. 2022 Mar;84(3):321-328. doi: 10.1016/j.jinf.2021.12.028. Epub 2021 Dec 24.

    PMID: 34958808DERIVED

  • Schaltz-Buchholzer F, Berendsen M, Roth A, Jensen KJ, Bjerregaard-Andersen M, Kjaer Sorensen M, Monteiro I, Aaby P, Stabell Benn C. BCG skin reactions by 2 months of age are associated with better survival in infancy: a prospective observational study from Guinea-Bissau. BMJ Glob Health. 2020 Sep;5(9):e002993. doi: 10.1136/bmjgh-2020-002993.

    PMID: 32978212DERIVED

Study Officials

  • Peter Aaby, Prof.

    Bandim Health Project

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 20, 2015

First Posted

May 19, 2015

Study Start

December 8, 2014

Primary Completion

November 24, 2017

Study Completion

May 1, 2018

Last Updated

December 16, 2020

Record last verified: 2020-12

Data Sharing

IPD Sharing
Will share

Locations

GU(1)