Condition category
Infections and Infestations
Date applied
17/01/2007
Date assigned
21/03/2007
Last edited
15/03/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The BCG vaccine protects against tuberculosis, a serious infection which affects the lungs. It has also been found to protect against leprosy, an infectious skin and nerve disease. The aim of this study is to assess the effectiveness of a second dose of BCG vaccination against tuberculosis and leprosy.

Who can participate?
Schoolchildren aged 7 to 14 years attending the participating state schools

What does the study involve?
Participating schools are randomly allocated to one of two groups: the intervention group and the control group. Participants in the intervention group schools receive a second BCG vaccination. Participants in the control group schools do not receive the second BCG vaccination. The number of cases of tuberculosis and leprosy are recorded in the two groups.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
767 state schools in the cities of Salvador and Manaus in Brazil

When is the study starting and how long is it expected to run for?
June 1996 to June 2016

Who is funding the study?
1. The Department For International Development (DFID) (UK)
2. Ministry of Health (Brazil)

Who is the main contact?
Prof. Mauricio Lima Barreto

Trial website

Contact information

Type

Scientific

Primary contact

Prof Mauricio Lima Barreto

ORCID ID

Contact details

Instituto de Saúde Coletiva
Universidade Federal da Bahia
Rua Basílio da Gama
s/n
Campus Universitário Canela
Salvador
40.110-040
Brazil

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

R6715

Study information

Scientific title

Trial of the efficacy of a second dose of BCG vaccination against tuberculosis (Avaliação da eficácia da segunda dose da vacina BCG em escolares)

Acronym

BCGREVAC

Study hypothesis

To estimate the efficacy of a second dose of BCG vaccination against tuberculosis and leprosy.

Ethics approval

1. Ethical Committee of the University Hospital Professor Edgard Santos (HUPES) of the Federal University of Bahia, 07/10/1996
2. National Committee for ethics in Research (Comitê Nacional de Etica em Pesquisa-CONEP), 30/10/2003, judgement ref: 770/2003, submission ref: 250000.106515/2003-02

Study design

Cluster randomised trial, with schools being the unit of randomisation. There was no concealment of allocation or intervention and no placebo was used.

Primary study design

Interventional

Secondary study design

Cluster randomised trial

Trial setting

Schools

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Tuberculosis and leprosy

Intervention

The intervention was a single intradermal injection with BCG vaccine produced in Brazil using the Moreaux (Rio de Janeiro) strain. This will be a revaccination as children have a high coverage of BCG at birth. The control group will receive no vaccination.

The trial was conducted in two sites, the cities of Salvador and Manaus, in Brazil. Seven hundred and sixty seven state schools were included in the trial. Children in both treatment groups were visited at school to confirm their identification details and their arms were examined for BCG scars. Ascertainment of cases was through the tuberculosis control programme. Cases notified were reviewed independently by two chest physicians, who classified cases into confirmed (microbiological confirmation), probable (would treat based on the information from the records), suspected (no information in the record suggested this was not tuberculosis) and not tuberculosis (excluded from the analysis), and into pulmonary and non-pulmonary forms. A third specialist reviewed those classified differently by the two chest physicians. The validation was blind to vaccination.

Cases were linked to the study population in the study database. Linkage was done blind to vaccination status, based on the name of the child, the name of the mother, the sex and date of birth of the child. All possible matches were reviewed by a member of the study team to assess its reliability. Most were unique matches, with complete concordance on all variables. Home visits to a sample of cases not linked to the database identified only two cases (out of 144 visited) that belonged to the database.

Active informed consent was not obtained. This was because both intervention (BCG revaccination) and absence of intervention were in routine practice in different settings in Brazil at the time, and therefore an "opt out" form of consent was deemed acceptable: parents of children in schools allocated to vaccination were given written information about the vaccine and the trial and offered the opportunity to withdraw their child from the trial.

Intervention type

Biological/Vaccine

Phase

Drug names

Primary outcome measures

1. Case of tuberculosis
2. Case of leprosy

Secondary outcome measures

1. Tuberculosis by form
2. Leprosy by form

Overall trial start date

01/06/1996

Overall trial end date

01/06/2016

Reason abandoned

Eligibility

Participant inclusion criteria

School children aged 7 to 14 years in state schools

Participant type

Other

Age group

Child

Gender

Both

Target number of participants

351,951

Participant exclusion criteria

1. Children with special needs
2. Children who received more than one BCG vaccination

Recruitment start date

01/06/1996

Recruitment end date

01/06/2016

Locations

Countries of recruitment

Brazil

Trial participating centre

Universidade Federal da Bahia
Salvador
40.110-040
Brazil

Sponsor information

Organisation

Institute for Collective Health (Instituto de Saúde Coletiva) (Brazil)

Sponsor details

c/o Maria da Gloria Lima Cruz Teixeira
Universidade Federal da Bahia
Rua Basílio da Gamas/n
Campus Universitário Canela
Salvador
40.110-040
Brazil
+55 (0)713 263 7414
magloria@ufba.br

Sponsor type

University/education

Website

http://www.isc.ufba.br/isc.asp

Funders

Funder type

Government

Funder name

Department for International Development

Alternative name(s)

Department for International Development, UK, DFID

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Funder name

Ministry of Health (Brazil)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2001 results in: http://www.ncbi.nlm.nih.gov/pubmed/11716343
2002 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/12392870
2003 results in: http://www.ncbi.nlm.nih.gov/pubmed/12729348
2003 results in: http://www.ncbi.nlm.nih.gov/pubmed/12700850
2004 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/15217320
2004 results in: http://www.ncbi.nlm.nih.gov/pubmed/15682973
2005 results in: http://www.ncbi.nlm.nih.gov/pubmed/16214599
2005 results in: http://www.ncbi.nlm.nih.gov/pubmed/16229231
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24852722

Publication citations

  1. Results

    Pereira SM, Dourado I, Barreto ML, Cunha SS, Ichiara MY, Hijjar MA, Goes JC, Rodrigues LC, Sensitivity and specificity of BCG scar reading in Brazil., Int. J. Tuberc. Lung Dis., 2001, 5, 11, 1067-1070.

  2. Protocol

    Barreto ML, Rodrigues LC, Cunha SS, Pereira S, Hijjar MA, Ichihara MY, de Brito SC, Dourado I, Design of the Brazilian BCG-REVAC trial against tuberculosis: a large, simple randomized community trial to evaluate the impact on tuberculosis of BCG revaccination at school age., Control Clin Trials, 2002, 23, 5, 540-553.

  3. Results

    Dourado I, Rios MH, Pereira SM, Cunha SS, Ichihara MY, Goes JC, Rodrigues LC, Bierrenbach AL, Barreto ML, Rates of adverse reactions to first and second doses of BCG vaccination: results of a large community trial in Brazilian schoolchildren., Int. J. Tuberc. Lung Dis., 2003, 7, 4, 399-402.

  4. Results

    Pereira SM, Bierrenbach AL, Dourado I, Barreto ML, Ichihara MY, Hijjar MA, Rodrigues LC, [Sensitivity and specificity of the BCG scar reading]., Rev Saude Publica, 2003, 37, 2, 254-259.

  5. Protocol

    Cunha SS, Dourado I, Barreto ML, Alexander N, Pereira SM, Ichihara Y, Pereira ES, Pedrosa V, Maroja F, Ribas C, Rodrigues LC, Design of the leprosy component of the Brazilian BCG revaccination trial for assessing BCG effectiveness against leprosy in school children., Int. J. Lepr. Other Mycobact. Dis., 2004, 72, 1, 8-15, doi: 10.1489/1544-581X(2004)072<0008:DOTLCO>2.0.CO;2.

  6. Results

    Cunha SS, Rodrigues LC, Pedrosa V, Dourado IM, Barreto ML, Pereira SM, Neonatal BCG protection against leprosy: a study in Manaus, Brazilian Amazon., Lepr Rev, 2004, 75, 4, 357-366.

  7. Results

    Rodrigues LC, Pereira SM, Cunha SS, Genser B, Ichihara MY, de Brito SC, Hijjar MA, Dourado I, Cruz AA, Sant'Anna C, Bierrenbach AL, Barreto ML, Effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: the BCG-REVAC cluster-randomised trial., Lancet, 2005, 366, 9493, 1290-1295, doi: 10.1016/S0140-6736(05)67145-0.

  8. Results

    Barreto ML, Cunha SS, Pereira SM, Genser B, Hijjar MA, Yury Ichihara M, de Brito SC, Dourado I, Cruz A, Santa'Ana C, Rodrigues LC, Neonatal BCG protection against tuberculosis lasts for 20 years in Brazil., Int. J. Tuberc. Lung Dis., 2005, 9, 10, 1171-1173.

  9. Results

    Barreto ML, Pilger D, Pereira SM, Genser B, Cruz AA, Cunha SS, Sant'Anna C, Hijjar MA, Ichihara MY, Rodrigues LC, Causes of variation in BCG vaccine efficacy: examining evidence from the BCG REVAC cluster randomized trial to explore the masking and the blocking hypotheses., Vaccine, 2014, 32, 30, 3759-3764, doi: 10.1016/j.vaccine.2014.05.042.

Additional files

Editorial Notes

15/03/2016: Plain English summary added.