Clinical trial NCT00514891: Impact of the WHO Recommended Vitamin A Supplementation at Immunisation Contacts
Official title: Evaluation of the Impact on Mortality and Morbidity of the WHO Recommended Vitamin A Supplementation at First Immunisation Contact After 6 Months of Age
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Mortality
Morbidity
Lead sponsor: Bandim Health Project
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Guinea-Bissau
name: University of Aarhus
First posted: 2007-08-10
Enrollment: 9500
Sex: ALL
Minimum age (years): 6
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mortality, morbidity
timeFrame: 1 year
Secondary outcomes:
measure: Growth, Vitamin A status, Immunology
Other outcomes:
Locations:
city: Bissau
country: Guinea-Bissau
facility: Bandim Health Project, Apartado 861
Study officials:
affiliation: Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark
name: Christine S Benn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bandim Health Project, Apartado 861, 1004 Bissau Codex, Guinea-Bissau
name: Peter Aaby, Dr.Med.
role: STUDY_DIRECTOR
References:
citation: Fisker AB, Bale C, Rodrigues A, Balde I, Fernandes M, Jorgensen MJ, Danneskiold-Samsoe N, Hornshoj L, Rasmussen J, Christensen ED, Bibby BM, Aaby P, Benn CS. High-dose vitamin A with vaccination after 6 months of age: a randomized trial. Pediatrics. 2014 Sep;134(3):e739-48. doi: 10.1542/peds.2014-0550.
citation: Fisker AB, Bale C, Jorgensen MJ, Balde I, Hornshoj L, Bibby BM, Aaby P, Benn CS. High-dose vitamin A supplementation administered with vaccinations after 6 months of age: sex-differential adverse reactions and morbidity. Vaccine. 2013 Jun 28;31(31):3191-8. doi: 10.1016/j.vaccine.2013.04.072. Epub 2013 May 14.
citation: Danneskiold-Samsoe N, Fisker AB, Jorgensen MJ, Ravn H, Andersen A, Balde ID, Leo-Hansen C, Rodrigues A, Aaby P, Benn CS. Determinants of vitamin a deficiency in children between 6 months and 2 years of age in Guinea-Bissau. BMC Public Health. 2013 Feb 25;13:172. doi: 10.1186/1471-2458-13-172.