Infant MortalityPhase 4NCT00168610
Vitamin A Supplementation With Bacille Calmette Guerin (BCG) Vaccine
A Phase 4 study testing Vitamin A in people with Infant Mortality and Morbidity, run by Bandim Health Project at 1 site in Guinea-Bissau.
Trial summary
In the present study the investigators wish to address the effects of different doses of vitamin A supplementation in low and normal birth weight infants. Hypotheses: Vitamin A supplementation administered at birth together with BCG vaccination is associated with a 30% reduction in infant mortality and morbidity… Read more about this study
- Who is it for?
- Ages Up to 5 months
- Conditions the study is for
- Infant Mortality, Morbidity
- What is being tested?
- Vitamin A
- How many people
- 7,600 participants
- Where
- 1 siteGuinea-Bissau
- Study dates
- Nov 2004to not given
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 5 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Normal birth weight: belonging to the study area
- Low birth weight: being born at the national hospital
Who cannot join
- Overt illness
- Signs of vitamin A deficiency
- Previous BCG vaccination
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Should Infants Receive High-dose Vitamin A Supplementation With BCG Vaccine at Birth in Developing Countries? Randomized Prospective Studies in Guinea-Bissau
In the present study the investigators wish to address the effects of different doses of vitamin A supplementation in low and normal birth weight infants.
Hypotheses:
- Vitamin A supplementation administered at birth together with BCG vaccination is associated with a 30% reduction in infant mortality and morbidity during the first year of life in both normal and low birth weight infants.
- A lower dose of vitamin A may be even more beneficial than a high dose.
Read the detailed description
Vitamin A deficiency is common in low-income countries. Vitamin A supplementation to children above 6 months of age reduces all-cause mortality by 23% to 30%. Studies on vitamin A supplementation in infants younger than 6 months of age have reported inconsistent effects on mortality. Studies providing supplementation between 1 and 5 months of age have found no effect or even a negative effect. However, the only two studies of supplementation at birth, both conducted in Asia, showed substantial significant reductions in infant all-cause mortality.
The beneficial effect of neonatal vitamin A supplementation may be a result of correcting the congenital vitamin A deficiency resulting from maternal vitamin A deficiency. On the other hand, it has been speculated that the beneficial effect of vitamin A supplementation given at birth may in part be explained by a synergistic effect of vitamin A supplementation and BCG vaccination given at the time of birth.
The protective effect on mortality of vitamin A supplementation given at birth needs to be confirmed in an African population. Furthermore, none of the two previous studies have reported data on the vaccination status of the included infants.
In the proposed studies, the effect on mortality and morbidity of giving vitamin A supplementation simultaneously with BCG vaccination at birth to both normal and low birth weight infants will be investigated in an African population. Furthermore, the effects of vitamin A supplementation will be evaluated with respect to effect on growth, the response to BCG vaccination, infant vitamin A status and infant cytokine profile, malaria, measles, rotavirus infection and RSV infection. The mechanisms behind the effects of vitamin A will be evaluated. The potential interactions between vitamin A, sex and vaccines will be taken into account in all analyses.
This will be done in two studies of newborn children. Study A includes 6,000 normal birth weight infants (> 2500 g) randomized to 50,000 or 25,000 IU vitamin A or placebo given simultaneously with BCG vaccine. Study B includes 1,600 low birth weight infants (< 2500 g) randomized to vitamin A or placebo and early BCG or late BCG in a two-by-two factorial design. The studies take place in Guinea-Bissau, West Africa. The study area consists of five districts in the capital of Guinea-Bissau. The Bandim Health Project has been working in the study area for almost 25 years, and a demographic surveillance system has been established and has functioned for many years.
- Conditions
- Infant Mortality, Morbidity
- Being tested
- Vitamin A
- Keywords
- Vitamin A, BCG, Infant mortality, Morbidity, Low-income country, Mortality
- Medical subject headings
- Infant Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin ADrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
Morbidity
Secondary outcomes (11)
Adverse effects
Tuberculin reaction
BCG scarring
Growth
Vitamin A status
Cytokine responses
Malaria
Measles
Rotavirus
Respiratory syncytial virus (RSV) infection
All primary and secondary outcomes will be analysed for interactions between vitamin A and sex and last vaccine received.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startNov 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Infant MortalityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Double blind
- Enrolment
- 7,600 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bandim Health Project
- Sponsor type
- University, hospital or other
- Collaborators
- March of Dimes, Leiden University Medical Center, Medical Research Council Unit, The Gambia
- Investigators
- Peter Aaby, Principal investigator, Bandim Health Project
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00168610
- Sponsor's protocol ID
- 6-FY04-51-VITA2
- Other IDs
- 6-FY04-51
- Status last verified
- Nov 2013
- First submitted
- 9 Sep 2005
- Last updated
- 15 Nov 2013
- Results posted
- No
Publications
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.
PubMed 32978212Schaltz-Buchholzer F, Biering-Sorensen S, Lund N, Monteiro I, Umbasse P, Fisker AB, Andersen A, Rodrigues A, Aaby P, Benn CS. Early BCG Vaccination, Hospitalizations, and Hospital Deaths: Analysis of a Secondary Outcome in 3 Randomized Trials from Guinea-Bissau. J Infect Dis. 2019 Jan 29;219(4):624-632. doi: 10.1093/infdis/jiy544.
PubMed 30239767Benn CS, Martins CL, Fisker AB, Diness BR, Garly ML, Balde I, Rodrigues A, Whittle H, Aaby P. Interaction between neonatal vitamin A supplementation and timing of measles vaccination: a retrospective analysis of three randomized trials from Guinea-Bissau. Vaccine. 2014 Sep 22;32(42):5468-74. doi: 10.1016/j.vaccine.2014.07.090. Epub 2014 Aug 13.
PubMed 25131735Benn CS, Diness BR, Balde I, Rodrigues A, Lausch KR, Martins CL, Fisker AB, Aaby P. Two different doses of supplemental vitamin A did not affect mortality of normal-birth-weight neonates in Guinea-Bissau in a randomized controlled trial. J Nutr. 2014 Sep;144(9):1474-9. doi: 10.3945/jn.114.192674. Epub 2014 Jul 2.
PubMed 24991044Biering-Sorensen S, Fisker AB, Ravn H, Camala L, Monteiro I, Aaby P, Benn CS. The effect of neonatal vitamin A supplementation on growth in the first year of life among low-birth-weight infants in Guinea-Bissau: two by two factorial randomised controlled trial. BMC Pediatr. 2013 May 23;13:87. doi: 10.1186/1471-2431-13-87.
PubMed 23702185Benn CS, Fisker AB, Napirna BM, Roth A, Diness BR, Lausch KR, Ravn H, Yazdanbakhsh M, Rodrigues A, Whittle H, Aaby P. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial. BMJ. 2010 Mar 9;340:c1101. doi: 10.1136/bmj.c1101.
PubMed 20215360
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Should Infants Receive High-dose Vitamin A Supplementation With BCG Vaccine at Birth in Developing Countries? Randomized Prospective Studies in Guinea-Bissau
- ClinicalTrials.gov ID
- NCT00168610
- Acronym / sponsor ID
- 6-FY04-51-VITA2
- Conditions
- Infant Mortality, Morbidity
- Keywords
- Vitamin A, BCG, Infant mortality, Morbidity, Low-income country, Mortality
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 7,600 participants (actual)
- Lead sponsor
- Bandim Health ProjectUniversity, hospital or other
- Collaborators
- March of Dimes, Leiden University Medical Center, Medical Research Council Unit, The Gambia
- Study start
- Nov 2004
- First posted
- 15 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the present study the investigators wish to address the effects of different doses of vitamin A supplementation in low and normal birth weight infants.
Hypotheses:
- Vitamin A supplementation administered at birth together with BCG vaccination is associated with a 30% reduction in infant mortality and morbidity during the first year of life in both normal and low birth weight infants.
- A lower dose of vitamin A may be even more beneficial than a high dose.
Detailed description
Vitamin A deficiency is common in low-income countries. Vitamin A supplementation to children above 6 months of age reduces all-cause mortality by 23% to 30%. Studies on vitamin A supplementation in infants younger than 6 months of age have reported inconsistent effects on mortality. Studies providing supplementation between 1 and 5 months of age have found no effect or even a negative effect. However, the only two studies of supplementation at birth, both conducted in Asia, showed substantial significant reductions in infant all-cause mortality.
The beneficial effect of neonatal vitamin A supplementation may be a result of correcting the congenital vitamin A deficiency resulting from maternal vitamin A deficiency. On the other hand, it has been speculated that the beneficial effect of vitamin A supplementation given at birth may in part be explained by a synergistic effect of vitamin A supplementation and BCG vaccination given at the time of birth.
The protective effect on mortality of vitamin A supplementation given at birth needs to be confirmed in an African population. Furthermore, none of the two previous studies have reported data on the vaccination status of the included infants.
In the proposed studies, the effect on mortality and morbidity of giving vitamin A supplementation simultaneously with BCG vaccination at birth to both normal and low birth weight infants will be investigated in an African population. Furthermore, the effects of vitamin A supplementation will be evaluated with respect to effect on growth, the response to BCG vaccination, infant vitamin A status and infant cytokine profile, malaria, measles, rotavirus infection and RSV infection. The mechanisms behind the effects of vitamin A will be evaluated. The potential interactions between vitamin A, sex and vaccines will be taken into account in all analyses.
This will be done in two studies of newborn children. Study A includes 6,000 normal birth weight infants (> 2500 g) randomized to 50,000 or 25,000 IU vitamin A or placebo given simultaneously with BCG vaccine. Study B includes 1,600 low birth weight infants (< 2500 g) randomized to vitamin A or placebo and early BCG or late BCG in a two-by-two factorial design. The studies take place in Guinea-Bissau, West Africa. The study area consists of five districts in the capital of Guinea-Bissau. The Bandim Health Project has been working in the study area for almost 25 years, and a demographic surveillance system has been established and has functioned for many years.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- Up to 5 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Normal birth weight: belonging to the study area
- Low birth weight: being born at the national hospital
Key exclusion criteria (3 listed)
- Overt illness
- Signs of vitamin A deficiency
- Previous BCG vaccination
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin A | Drug | – |
Primary outcome
Mortality
Morbidity
11 secondary outcomes
Adverse effects
Tuberculin reaction
BCG scarring
Growth
Vitamin A status
Cytokine responses
Malaria
Measles
Rotavirus
Respiratory syncytial virus (RSV) infection
All primary and secondary outcomes will be analysed for interactions between vitamin A and sex and last vaccine received.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2013.
- Derived from this study: PubMed 32978212Schaltz-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.
- Derived from this study: PubMed 30239767Schaltz-Buchholzer F, Biering-Sorensen S, Lund N, Monteiro I, Umbasse P, Fisker AB, Andersen A, Rodrigues A, Aaby P, Benn CS. Early BCG Vaccination, Hospitalizations, and Hospital Deaths: Analysis of a Secondary Outcome in 3 Randomized Trials from Guinea-Bissau. J Infect Dis. 2019 Jan 29;219(4):624-632. doi: 10.1093/infdis/jiy544.
- Derived from this study: PubMed 25131735Benn CS, Martins CL, Fisker AB, Diness BR, Garly ML, Balde I, Rodrigues A, Whittle H, Aaby P. Interaction between neonatal vitamin A supplementation and timing of measles vaccination: a retrospective analysis of three randomized trials from Guinea-Bissau. Vaccine. 2014 Sep 22;32(42):5468-74. doi: 10.1016/j.vaccine.2014.07.090. Epub 2014 Aug 13.
- Derived from this study: PubMed 24991044Benn CS, Diness BR, Balde I, Rodrigues A, Lausch KR, Martins CL, Fisker AB, Aaby P. Two different doses of supplemental vitamin A did not affect mortality of normal-birth-weight neonates in Guinea-Bissau in a randomized controlled trial. J Nutr. 2014 Sep;144(9):1474-9. doi: 10.3945/jn.114.192674. Epub 2014 Jul 2.
- Derived from this study: PubMed 23702185Biering-Sorensen S, Fisker AB, Ravn H, Camala L, Monteiro I, Aaby P, Benn CS. The effect of neonatal vitamin A supplementation on growth in the first year of life among low-birth-weight infants in Guinea-Bissau: two by two factorial randomised controlled trial. BMC Pediatr. 2013 May 23;13:87. doi: 10.1186/1471-2431-13-87.
- Derived from this study: PubMed 20215360Benn CS, Fisker AB, Napirna BM, Roth A, Diness BR, Lausch KR, Ravn H, Yazdanbakhsh M, Rodrigues A, Whittle H, Aaby P. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial. BMJ. 2010 Mar 9;340:c1101. doi: 10.1136/bmj.c1101.
Related trials for Infant Mortality
Active, not recruitingPhase 4
Oral Azithromycin to Prevent Stillbirths and Infant Mortality in Mali
Stillbirths and Infant Mortality
Not yet recruiting
Perinatal Mortality Outcomes Through Household Infection Pathways
Stillbirth and Neonatal Mortality, Perinatal Mortality
Active, not recruitingPhase 4
Can BCG Vaccination at First Health-facility Contact Reduce Early Infant Mortality?
Infant Mortality, BCG
RecruitingObservational study
Biological Impacts of Rising Temperatures on Maternal, Fetal, and Newborn Health: A Cohort Study (BIRTH Cohort)
Low Birth Weight Baby, Small for Gestational Age (SGA)
Enrolling by invitationPhase 4
BCG Revaccination With the Third Dose of Diphtheria-tetanus-pertussis Vaccine and Infant Mortality in Africa
Infant Morbidity, Infant Mortality
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Aaby principal investigator
Bandim Health Project
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vitamin A in people with Infant Mortality and Morbidity, 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 2 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 15 Nov 2013. 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?
Results are not available in the source record.
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?
Mortality. The study lists 2 primary outcomes in all. 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 NCT00168610, which also lists 6 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 15 Nov 2013; AzTrials last refreshed its copy on 8 Nov 2026.