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Infant MortalityPhase 4BCGRNCT02504203

Can Earlier BCG Vaccination Reduce Early Infant Mortality? A Randomised Trial

A Phase 4 study testing BCG-Denmark 1331 (Statens Serum Institute) in people with Infant Mortality and BCG, run by Bandim Health Project at 1 site in Guinea-Bissau.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to determine whether BCG vaccination shortly after birth can reduce early infant mortality in a rural and an urban setting. Read more about this study

Who is it for?
Ages Up to 72 hoursHealthy volunteers can take part
Conditions the study is for
Infant Mortality, BCG
What is being tested?
BCG-Denmark 1331 (Statens Serum Institute)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2,332 participants
Where
1 siteGuinea-Bissau
Study dates
Nov 2015to Jun 2021
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 72 hours
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • All children registered during pregnancy will be eligible for the study provided they have not yet received BCG at the date of the home visit.

Who cannot join

  • Children born outside the cluster, and returning more than 72 hours after the delivery
  • Children that the nurse evaluates to die within the next 24 hours.

Trial locations and contacts

1 site in 1 country.

Guinea-Bissau1 site
  • Bandim Health Project

    Bissau

Other trials in Guinea-Bissau

About this study

The purpose of this study is to determine whether BCG vaccination shortly after birth can reduce early infant mortality in a rural and an urban setting.

Read the detailed description

Background: BCG and oral polio vaccines (OPV) at birth are associated with beneficial non-specific effects, reducing neonatal mortality by more than what can be explained by prevention of the target diseases. BCG is recommended at birth, but is often given much later, especially in rural areas. In two RCTs in Guinea-Bissau, BCG-at-birth reduced neonatal mortality in low birthweight (<2500g; LBW) children by 48% (95%CI: 18-67%) and in children with a birthweight >2500g (NBW), OPV+BCG vs BCG was associated with a 32% (95%CI: 0-55%) lower mortality.

WHO recommends home visits shortly after birth to reduce mortality, but vaccinations are not normally provided. If the vaccines indeed have profound effects on innate immunity and neonatal mortality in both LBW and NBW children many lives could be saved if BCG and OPV was provided earlier. Urban and rural clusters are randomised to home visits with and without vaccinations. All children participating in the study will be offered routine vaccines at village visits by the BHP team in the rural area. In the urban area, BCG and OPV will be provided at follow-up visits if the child has not yet received the vaccines. Thereby the study will provide earlier vaccination for all children.

Hypothesis: BCG+OPV at birth provided at village visits shortly after birth will reduce early infant mortality by 40%.

Methods: The study will be conducted in Biombo, Oio and Cacheu in rural Guinea-Bissau and in six suburban districts in the capital of Guinea-Bissau. In Guinea-Bissau home visits are not yet implemented as part of the routine program. Pregnant women will be offered to participate in the study at the time of pregnancy registration, which is conducted as part of the routine registration in the rural and urban health and demographic surveillance systems, respectively. Community key informants or mothers will communicate information on births to the BHP study team, and a study nurse will visit every new-born child shortly after a CKI or mother calls, if possible on the same day. Clusters will be randomised to receive immediate vaccination of their children shortly after birth or at the first visit by the BHP team in the rural area and at 2-months follow-up visits in the urban area.

Statistical analyses: The primary analysis of early infant non-accidental mortality will be assessed on a PP analysis stratifying for factors used in the randomization (Region, pre-study mortality level (high/low)) and sex, thus allowing different baseline hazards for boys and girls. To account for clustering we will employ cluster-robust variance estimates.

For the primary outcome, we will use Cox proportional hazards models, stratified for the above mentioned factors and with age as underlying time-scale. Deaths due to accidents will be censored.

The effect of early vaccination will be assessed for the following secondary outcomes:

  • Non-accidental hospital admission
  • Severe morbidity (composite outcome of non-accidental mortality and non-accidental hospital admissions)
  • Consultations
  • Growth
  • Mid-upper-arm circumference
  • Weight-for-age z-score
  • BCG scarring
  • Cost-effectiveness of providing BCG and OPV at home visits

Based on previous data from the rural HDSS in the areas where the current study will be conducted, the expected proportion of events (deaths and hospitalisation) between day 1 and the next home visit or 60 days of age, whichever comes first is 2.4% (unpublished data). The proportion of events are expected to be at least as high in the urban area. A recent trial in Ghana indicated that three home visits during the first week of life to promote essential new-born care practices and to weigh and assess children for danger signs was associated with an 8% (-12 to 25%) reduction in neonatal mortality. Based on pre-trial mortality data from the same rural clusters, the design effect is measured to be 1.43 (ratio of square of the standard errors for the cluster-adjusted/unadjusted HRs). Thus, in order to obtain 80% power to detect a reduction in early infant severe morbidity if the true reduction of BCG and OPV provided at home visits is larger than 40%, at least 6666 children need to be enrolled.

Being tested
BCG-Denmark 1331 (Statens Serum Institute)
Medical subject headings
Infant Death

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BCG-Denmark 1331 (Statens Serum Institute)Biological

    Also called BCG-Japan (Japan BCG Laboratory)

    See above

Study groups in NCT02504203
Study groupRoleWhat they receive
Intervention: BCG and OPV at home visitsActive comparatorInfants randomised to receive vaccines at home visits shortly after birth will receive one 0.05 ml dose of Mycobacterium bovis BCG live attenuated vaccine (BCG-Denmark 1331 (Statens Serum Institute) or BCG Japan (Japan BCG Laboratory) 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. For all children, the nurse will perform umbilical cord and skin care, encourage skin-to-skin contact to keep the new-born warm, examine and weigh the child at a home visit shortly after birth.
Receives: Biological: BCG-Denmark 1331 (Statens Serum Institute)
Control: No vaccines at home visitsNo interventionFor all children, the nurse will perform umbilical cord and skin care, encourage skin-to-skin contact to keep the new-born warm, examine and weigh the child at a home visit shortly after birth. No vaccines will be administered at these home visits for children in the control arm.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Non-accidental Mortality

    Non-accidental mortality between the home visit and the next follow-up visit by BHP, when all unvaccinated children who are home will be offered BCG or the date of registering a non-trial vaccine or 60 days, whichever comes first.

    Measured: 60 days after birth

Secondary outcomes (8)
  1. Non-accidental Hospital Admission

    Non-accidental hospital admission between the home visit and the next follow-up visit by BHP, when all unvaccinated children who are home will be offered BCG or the date of registering a non-trial vaccine or 60 days, whichever comes first.

    Measured: 60 days after birth

  2. Severe Morbidity

    Composite outcome of non-accidental mortality and non-accidental hospital admissions

    Measured: 60 days after birth

  3. All-cause Consultations

    All-cause out-patient consultation between the home visit and the next follow-up visit by BHP, when all unvaccinated children who are home will be offered BCG or the date of registering a non-trial vaccine or 60 days, whichever comes first.

    Measured: 60 days after birth

  4. Mid-upper-arm Circumference

    Development in mid-upper-arm circumference measured using a TALC insertion tape between enrollment and first visit by the BHP team will be assessed.

    Measured: 60 days after birth

  5. Weight-for-age Z-score

    Development in weight between enrolment and first visit by the BHP team will be assessed using the WHO Child Growth Standards. These standards were developed using data collected in the WHO Multicentre Growth Reference Study. A child with a weight-for-age Z-score of 0 has a weight-for-age corresponding to the reference mean. A negative z-score indicates that the childs weight-for-age is below the reference mean, while a child with a positive score is above the mean.

    Measured: 60 days after birth

  6. BCG Scarring

    Development of a BCG vaccination scar (yes/no) will be assessed.

    Measured: 6 months after birth

  7. Cost-effectiveness Analysis of Providing BCG at Home-visits

    A cost effectiveness analysis seeking to measure the cost per death averted using a societal perspective, contrasting the costs of vaccine provision in the present programme and an outreach system as tested in the trial. The costs/savings associated with different rates of consultations and admissions will also be taken into account.

    Measured: 60 days after birth

  8. Cause Specific Mortality

    For every death a verbal autopsy will be made

    Measured: 60 days after birth

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2015 (estimated)
  2. Study startNov 2015
  3. Primary completionJun 2021
  4. Study completionJun 2021

Why it stopped: Due to fewer than expected children enrolled and lower than expected overall mortality rate.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
2,332 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02504203
Sponsor's protocol ID
BCG150501
Acronym
BCGR
Status last verified
Feb 2026
First submitted
20 Jul 2015
Last updated
26 May 2026
Data monitoring committee
Yes

Publications

  • Thysen SM, da Silva Borges I, Martins J, Stjernholm AD, Hansen JS, da Silva LMV, Martins JSD, Jensen A, Rodrigues A, Aaby P, Stabell Benn C, Fisker AB. Can earlier BCG-Japan and OPV vaccination reduce early infant mortality? A cluster-randomised trial in Guinea-Bissau. BMJ Glob Health. 2024 Feb 12;9(2):e014044. doi: 10.1136/bmjgh-2023-014044.

    PubMed 38350670
  • 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.

    PubMed 21673035
  • 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.

    PubMed 22189537
  • Thysen SM, Byberg S, Pedersen M, Rodrigues A, Ravn H, Martins C, Benn CS, Aaby P, Fisker AB. BCG coverage and barriers to BCG vaccination in Guinea-Bissau: an observational study. BMC Public Health. 2014 Oct 4;14:1037. doi: 10.1186/1471-2458-14-1037.

    PubMed 25282475
  • Thysen SM, Jensen AKG, Rodrigues A, Borges IDS, Aaby P, Benn C, Fisker A. Can earlier BCG vaccination reduce early infant mortality? Study protocol for a cluster randomised trial in Guinea-Bissau. BMJ Open. 2019 Sep 24;9(9):e025724. doi: 10.1136/bmjopen-2018-025724.

    PubMed 31551370

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing BCG-Denmark 1331 (Statens Serum Institute) in people with Infant Mortality and BCG, run by Bandim Health Project at 1 site in Guinea-Bissau.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Guinea-Bissau. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Non-accidental Mortality (time frame: 60 days after birth). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02504203, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2026.

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