Efficacy of Newborn Vitamin A Supplementation Versus Placebo in Improving Child Survival (NeoVitA Trial)

Study Overview
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Brief Summary
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The study is a large randomized controlled trial to assess the efficacy and safety of neonatal vitamin A supplementation administered to neonates once orally either on the day of birth or in the next 2 days in improving infant survival in the first 6 months of life.

Detailed Description
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The study is an individually randomized trial conducted in two districts in the state of Haryana. Community informants report births to the enrolment team. At enrolment, the team explains the study to the family and in those willing, written consent is obtained from the parents of the infant. The infant is given the dose of vitamin A/placebo and a form containing baseline socioeconomic characteristics and information on feeding practices of the infant and mother is filled. After enrollment, each infant is visited by the enrollment team at hospital or home 1 day and 3 days after supplementation to document any illnesses in the baby. Newborns with illnesses are referred/escorted to the nearest health facility for management. Enrolled infants are visited when aged 29 days, 3, 6 and 12 months to document vital status and hospitalizations since the last visit. Information on feeding practices, immunization, maternal intake of vitamin A rich foods and supplements, and intake of any supplement containing vitamin A by the infant is recorded at these visits. Subgroup analyses includes the effect of vitamin A supplementation in LBW and non LBW infants, male and female infants, immunized and unimmunized infants, infants of families in the poorest and richest quintiles and by vitamin A intake of mothers. For all deaths, verbal autopsy interviews are conducted. Blood specimens are obtained in a subsample of infants at 2 weeks and 3 months of age and in a subsample of mothers at 3 months of age. Quality control activities include independent and supervised checks and are conducted for a subsample by a separate team. A DSMB has been constituted for the study. All deaths occurring within 72 hours of supplementation will be reported to the SAS ERC and to the WHO Coordinating Unit. At the recent DSMB meeting in February 2012, the DSMB recommended an increase in sample size to 45,000 instead of the earlier estimate of 40,200 because of somewhat lower than expected mortality rates. This increase in sample size is expected to preserve the specified power of 0.85 and the corresponding level of precision anticipated at the design stage. Similar trials are being funded by the World Health Organization (Geneva) in Ghana and Tanzania.

Official Title
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Efficacy of Neonatal Vitamin A Supplementation in Improving Child Survival in Haryana, India: Generation of Evidence Necessary for Informing Global Policy

Conditions
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Neonatal Vitamin A Supplementation

Intervention / Treatment
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* Drug: Vitamin A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consent to participate All births in the study area that are contacted by enrolment team within the eligible age window Exclusion Criteria: Unable to feed on offering feeds, as reported by the mother Mother does not intend to stay in the study area for at least 6 months

Ages Eligible for Study
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Minimum Age: 2 Hours
Maximum Age: 72 Hours

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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin A<br>Vitamin A capsules have retinol palmitate (50,000 IU) and minute amounts of vitamin E in soybean oil | Drug: Vitamin A<br>* Retinol palmitate (50,000 IU) and minute amounts of vitamin E in soybean oil, orally as a single dose to neonates on the day of birth or in the next 2 days of birth keeping a minimum period of 2 hours between the birth and the dosing<br>|
| Placebo Comparator: Placebo<br>Placebo capsules contain minute amounts of vitamin E in soybean oil | Drug: Vitamin A<br>* Retinol palmitate (50,000 IU) and minute amounts of vitamin E in soybean oil, orally as a single dose to neonates on the day of birth or in the next 2 days of birth keeping a minimum period of 2 hours between the birth and the dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of death | To determine if vitamin A supplementation (50,000 IU) given to neonates once orally either on the day of birth or in the next 2 days will reduce mortality in the first half of infancy as compared to placebo. | Period between receiving the intervention/placebo and six months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of death | To determine the efficacy of vitamin A supplementation (50,000 IU) given to neonates once orally either on the day of birth or in the next 2 days in reducing mortality in the neonatal period (first month of life). | Period between receiving the intervention/placebo and 28 days of age | 
| Risk of death | To determine the efficacy of vitamin A supplementation (50,000 IU) given to neonates once orally either on the day of birth or in the next 2 days in reducing mortality at 12 months. | Period between receiving the intervention/placebo and 12 months of age | 
| Risk of hospital admission | To determine the efficacy of the above intervention in reducing the incidence of severe morbidity defined as hospitalizations due to any illness in the first 6 months of infancy. | Period between receiving the intervention/placebo and six months of age | 
| Bulging fontanelle, vomiting, irritability, fever, diarrhea, inability to suck or feed, convulsions or any other conditions that caused parents to be concerned | To assess bulging fontanelle, vomiting, irritability, fever, diarrhea, inability to suck or feed, convulsions or any other conditions that caused parents to be concerned, in the 3 day period following administration of the supplement | Three day period following supplementation | 
| Vitamin A status in a subgroup of newborns and caregivers in the intervention and placebo groups | To determine vitamin A status in a subsample of infants and caregivers in the intervention and placebo groups at 2 weeks and 3 months of age in the vitamin A supplementation and placebo groups | Two weeks and three months of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin A, Neonatal mortality, Infant mortality