Impact of the WHO Recommended Vitamin A Supplementation at Immunisation Contacts

Study Overview
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Brief Summary
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High-dose vitamin A to children above 6 months of age reduces all-cause mortality by 23-30%. The WHO recommends vitamin A supplementation (VAS) with the first vaccine after 6 months of age. However, the effect of providing VAS with vaccines has never been investigated. We have hypothesised that the effect of VAS depends on the immune stimulus at the time of supplementation. Hence, the effect might vary depending on which type of vaccine it is given with. In particular, we hypothesised that VAS might be beneficial when given with measles vaccine but not when given with DTP vaccine. Normally the first vaccine after 6 months of age would be a measles vaccine, but many children come late for their DTP vaccinations and receive DTP alone or together with measles vaccine. Hence, it is important to study whether the effect of VAS is the same irrespective of the vaccine(s) administered at the same time. Guinea-Bissau has not yet implemented the WHO vitamin A policy of providing VAS with vaccines, but plans to do so within the next years. Together with the Ministry of Health in Guinea-Bissau, the Bandim Health Project (BHP) in Guinea-Bissau will investigate the effect on mortality and morbidity of implementing the WHO vitamin A policy in Guinea-Bissau. This will be done in a large randomised trial. BHP has a demographic surveillance system (DSS) which has followed a population of now more than 150,000 individuals for almost 30 years. Children will be randomised to receive VAS or placebo with their first vaccine after 6 months of age, and will be followed through the DSS to assess mortality and morbidity. Based on previous observations, the effects of VAS might differ according to sex and season. The interaction between VAS, sex, and season will also be studied in the present trial. By identifying situations where VAS may be beneficial, ineffective, or even harmful the study may contribute importantly to optimising the VAS policy for low-income countries.

Official Title
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Evaluation of the Impact on Mortality and Morbidity of the WHO Recommended Vitamin A Supplementation at First Immunisation Contact After 6 Months of Age

Conditions
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Mortality, Morbidity

Intervention / Treatment
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* Biological: Vitamin A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Urban area: 6-17-month-old children, presenting for vaccination at a health centre in the study area. Rural area: 6-23-month-old children who are missing one or more routine vaccinations when visited by our mobile team. Exclusion Criteria: Normally applied contraindications for receiving vaccinations, including high fever. VAS within last month.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 23 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Vitamin A supplementation | Biological: Vitamin A<br>* The effect of vitamin A given with different vaccines will be studied<br>|
| Placebo Comparator: 2<br>Placebo | Biological: Vitamin A<br>* The effect of vitamin A given with different vaccines will be studied<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality, morbidity |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth, Vitamin A status, Immunology |  |  |