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
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
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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.