Contact information
Type
Scientific
Contact name
Dr Tracey Goodman
ORCID ID
Contact details
World Health Organization
20 Avenue Appia
Geneva-27
CH-1211
Switzerland
goodmant@who.int
Additional identifiers
EudraCT/CTIS number
IRAS number
ClinicalTrials.gov number
Protocol/serial number
WHO/RPC005
Study information
Scientific title
Acronym
Study hypothesis
The primary objectives of the trial are to:
1. Measure the effect of 400,000 IU of vitamin A given in two divided doses of 200,000 to mothers, and 3 doses of 50,000 IU of vitamin A given to their infants concurrently with Diphtheria, Pertussis and Tetanus (DPT)/Polio immunisations, on vitamin A status of the infants at 26 weeks of age
2. Compare the effect of such a regimen to that of the previously recommended regimen of 200,000 IU of vitamin A given to mothers and 3 doses of 25,000 IU of vitamin A given to their infants concurrently with DPT/Polio immunisations
3. Measure the short-term side effects of each of the two doses of 200,000 IU given to mothers, and of the 50,000 IU of vitamin A administered with each of the three DPT/Polio immunisations
The secondary objectives are to:
1. Measure the relative effect of the two different maternal dosing regimens on the breast milk retinol concentration up to at 6 and 9 months post partum
2. Measure the effect of the maternal doses of vitamin A on the relative incidence of short-term side effects in the mother over the 48-hour period after the first and second 200,000 IU maternal doses of vitamin A
3. Measure the effect of the maternal doses of vitamin A on the breast milk retinoic acid concentration 3 hours after the first and second 200,000 IU maternal doses of vitamin A
4. Examine if any relative impacts on vitamin A status are sustained at 9 months of age
Related to the main objectives, the following hypotheses will be tested:
HYPOTHESIS 1: Giving 400,000 IU of vitamin A to mothers within 6 weeks of delivery, plus 50,000 IU given to their infants with their DPT/Polio immunisations, will improve infants' vitamin A status to a significantly greater degree than giving 200,000 IU of vitamin A within 6 weeks of delivery, plus 25,000 IU given to their infants with each of their three DPT/Polio immunisations. This will be measured by mean serum retinol concentration, or by proportions below 20ug/dl, or proportions with abnormal modified Retinol Dose Response (mRDR) at 6 months of age. The proportion of infants with serum retinol concentration below 20ug/dl at 6 months of age will be approximately 37% in the comparison group infants and 27% or less in the group of infants allocated to receive the higher dose regimen.
HYPOTHESIS 2: Giving 50,000 IU of vitamin A to infants with their DPT/Polio immunisations will produce no significant increase in the incidence of short-term side effects, relative to 25,000IU.
The outcomes to be monitored for the above objectives include serum retinol concentrations, mRDR tests, and incidence of side effects such as bulging of anterior fontanelle and vomiting, and incidence of severe morbidity.
HYPOTHESIS 3: Giving 400,000 IU of vitamin A to mothers in the post partum period will result in a greater improvement in breast milk retinol concentrations at 6 months post partum than that achieved with 200,000IU, and that this improvement will be sustained up to 9 months.
HYPOTHESIS 4: Giving a second 200,000 IU dose of vitamin A to mothers in the post partum period will result in no significant increase in the incidence of short-term side effects, relative to no second dose.
HYPOTHESIS 5: Giving a second 200,000IU dose of vitamin A to mothers in the post partum period will result in no significant increase in the prevalence of potentially toxic breast milk retinoic acid concentrations 3 hours after the second maternal dose, relative to no second dose.
HYPOTHESIS 6: At 9 months of age, the vitamin A status of infants who were allocated to receive the higher dose regimen will be significantly better than the status of infants who were allocated to receive the lower dose regimen.
Ethics approval(s)
Ethics approval received from the Research Ethics Committees (REC) of:
1. National Institute for Medical Research, Ministry of Health (Tanzania) on the 1st October 2001
2. Second year of trial approved by the London School of Hygiene and Tropical Medicine on the 5th August 2003
3. World Health Organization (WHO) Secretariat Committee on Research Involving Human Subjects (SCRIHS) - conditional approval on 11th April 2003, amendments approved on 8th October 2003
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Not specified
Study type
Prevention
Patient information sheet
Condition
Vitamin A deficiency
Intervention
1st Group:
1. Mothers 200,000 IU Vitamin A shortly after delivery
2. Infants: 25,000 IU Vitamin A with each Diphtheria, Pertussis, Tetanus (DPT) vaccine 1, 2 and 3
2nd Group:
1. Mothers 200,000 IU Vitamin A at infant's Bacillus Calmette-Guerin (BCG) vaccine and another 200,000 IU Vitamin A at infant's 1st DPT
2. Infants: 50,000 IU Vitamin A with each DPT 1, 2 and 3
Time Frame:
Recruitment should start in December 2001 and is expected to last for approximately 9 months. Hence the data required to address the primary endpoint will be available 15 months after the start of recruitment. Data required to address the secondary endpoints will be available 21 months after the start of recruitment. Assuming that the WHO-appointed micronutrient laboratory will be able to report the results of vitamin A-related analyses within six weeks of the completion of specimen collection, all laboratory and statistical analyses will be completed within 4 months of finishing field activities.
Intervention type
Supplement
Primary outcome measure
1. Prevalence of Vitamin A Deficiency (VAD) (any: less than 20 mg/dL and severe: less than 10 mg/dL) at 6 months of age
2. Incidence of each of the following:
2.1. Bulging fontanelle
2.2. Temperature greater than 37.5°C
2.3. Vomiting
2.4. Diarrhoea
2.5. Inability to suck/feed during the two days following each vitamin A supplementation
Secondary outcome measures
1. Mean serum retinol concentration at 6 months of age
2. Prevalence of VAD (any and severe) at 9 months of age
3. Mean retinol concentration at 9 months of age
Overall study start date
01/12/2001
Overall study end date
01/09/2003
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Mothers normally resident in the study area
2. Informed consent obtained from the mother
Participant type(s)
Patient
Age group
Child
Sex
Both
Target number of participants
770 infants
Participant exclusion criteria
1. Mothers unable to give informed consent
2. Mothers considered to be at high risk of adverse outcome in puerperal period
3. Multiple deliveries
4. Severe adverse reaction to vitamin A supplementation
Recruitment start date
01/12/2001
Recruitment end date
01/09/2003
Locations
Countries of recruitment
Switzerland, Tanzania
Study participating centre
World Health Organization
Geneva-27
CH-1211
Switzerland
Sponsor information
Organisation
World Health Organization (WHO)/Department of Immunisation, Vaccines and Biologicals (IVB) (Switzerland)
Sponsor details
20
Avenue Appia
Geneva-27
CH-1211
Switzerland
Sponsor type
Research organisation
Website
ROR
Funders
Funder type
Research organisation
Funder name
World Health Organization (WHO)/Department of Immunisation, Vaccines and Biologicals (IVB) (Switzerland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Not provided at time of registration
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|