Impact of the WHO Recommended Vitamin A Supplementation at Immunisation Contacts

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

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.

Study Overview

• Status: Terminated
• Conditions: Mortality; Morbidity
• Intervention / Treatment: Biological: Vitamin A

• Study Type: Interventional
• Enrollment (Anticipated): 9500
• Phase: Phase 4

Contacts and Locations

Study Locations

• Guinea-Bissau
  • Bissau, Guinea-Bissau
    • Bandim Health Project, Apartado 861

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; Placebo	Biological: Vitamin A; The effect of vitamin A given with different vaccines will be studied
Active Comparator: 1; Vitamin A supplementation	Biological: Vitamin A; The effect of vitamin A given with different vaccines will be studied

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mortality, morbidity	1 year

Secondary Outcome Measures

Outcome Measure
Growth, Vitamin A status, Immunology

Collaborators and Investigators

• Sponsor: Bandim Health Project
• Collaborators: University of Aarhus; Ministry of Health, Guinea-Bissau
• Investigators: Principal Investigator: Christine S Benn, MD, PhD, Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark; Study Director: Peter Aaby, Dr.Med., Bandim Health Project, Apartado 861, 1004 Bissau Codex, Guinea-Bissau

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Anticipated): June 1, 2012
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: August 8, 2007
• First Submitted That Met QC Criteria: August 9, 2007
• First Posted (Estimate): August 10, 2007

Study Record Updates

• Last Update Posted (Estimate): March 1, 2011
• Last Update Submitted That Met QC Criteria: February 26, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin A
• Other Study ID Numbers: CVK-2006-7041-99

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No