Trial of Additional Measles Vaccine to Reduce Child Mortality

Study Overview
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Brief Summary
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Background: All observational studies and a few randomised controlled trials (RCT) suggest that early measles vaccine (MV), in particular an early two-dose strategy, has a much better effect on overall mortality than later MV. These results suggest that MV has a non-measles related beneficial effect on child survival. Objective: To evaluate in a two-site RCT the effect on child survival and other health indicators of a two-dose measles vaccination schedule by providing an additional dose of Edmonston-Zagreb (EZ) MV as soon as possible after 4 months of age as well as the standard measles vaccine at 9 months of age. The trials are planned in Guinea-Bissau and Burkina Faso. The investigators will test a 40-43% reduction of mortality at each site separately and a 32% reduction overall. Based on the results from the RCT, the investigators will assess the cost-effectiveness of the intervention. Design, Guinea-Bissau: Newborns are followed through the Health and Demographic Surveillance System (HDSS) of the Bandim Health Project. Information on routine and campaign vaccinations will be collected regularly through home visits and health centre registers. Four weeks after having received the third dose of pentavalent vaccine (Penta3), the children will be eligible for enrollment in the trial if they are not severely ill. Eligible children will be invited to take part in the trial. Provided parental informed consent is given, the children will be randomised to MV at 4 and 9 months of age or only at 9 months. Cost estimates will be based on consumption of services and average cost per unit. The incremental cost effectiveness ratio will be calculated. Sample size, follow-up and analyses: To detect a 40% reduction in overall mortality at each site the investigators intend to enroll at least 3,750 children in Guinea-Bissau. The children will be followed for survival and hospitalisations to 3 years of age or to the end of the study after three years. The investigators will analyse the effects by site and combined; by sex and season; possible interactions with other interventions like campaigns with drugs, vaccines or micronutrients will be explored. Antibody study: 450 children will be enrolled in a subgroup study to examine the effect of maternal antibody levels on subsequent antibody responses to MV. The children will be followed to 24 months of age and samples collected at 4, 9 and 24 months of age.

Official Title
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A Two-site Randomised Trial of an Additional Measles Vaccine at 4 Months of Age to Reduce Child Mortality in Rural Areas of Burkina Faso and Guinea-Bissau

Conditions
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Measles Vaccine

Intervention / Treatment
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* Biological: Early measles vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children who received the third dose of pentavalent vaccine at least 28 days before enrolment are between 4 and 6 months old belong to households of the existing HDSS Exclusion Criteria: Children with serious malformation who are severely sick (needing hospitalisation) with high fever (>38.5 C axillary temperature) who are severely malnourished (mid-upper-arm-circumference (MUAC) < 110 mm and/or bilateral peripheral oedema) who have received neonatal vitamin A supplementation whose parents/guardians state that they intend to permanently move out of the study area before the child reaches 9 months of age

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early measles vaccine<br>An additional measles vaccine at 4 months of age, at least 28 days after the third dose of pentavalent vaccine | Biological: Early measles vaccine<br>* Standard Edmonston-Zagreb measles vaccine<br>|
| No Intervention: Control<br>Follows the normal vaccination schedule | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Overall mortality from 4 months to 3 years by sex and age at enrolment | 4 months - 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Mortality from 4 to 9 months of age and from 9 months to 3 years of age | 4 to 9 months of age and from 9 months to 3 years of age | 
| Morbidity | Hospital admissions, consultations, specific morbidity and measles infection | 4 months - 3 years of age | 
| Growth |  |  | 
| Antibody titres |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Child mortality, Measles vaccine, Non-specific effects