Trial of Additional Measles Vaccine to Reduce Child Mortality
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 multi-center 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. Three trials are planned in Guinea-Bissau, Ghana and Burkina Faso. The investigators will test a 50% 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 50% reduction in overall mortality at each site the investigators intend to enroll at least 2,250 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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Multi-site Randomised Trial of an Additional Measles Vaccine at 4 Months of Age to Reduce Child Mortality in Rural Areas of Burkina Faso, Ghana, and Guinea-Bissau. Guinea-Bissau Protocol.|
- Mortality [ Time Frame: 4 months - 3 years ] [ Designated as safety issue: No ]Overall mortality from 4 months to 3 years by sex and age at enrolment
- Mortality [ Time Frame: 4 to 9 months of age and from 9 months to 3 years of age ] [ Designated as safety issue: No ]Mortality from 4 to 9 months of age and from 9 months to 3 years of age
- Morbidity [ Time Frame: 4 months - 3 years of age ] [ Designated as safety issue: No ]Hospital admissions, consultations, specific morbidity and measles infection
- Antibody titres
- Immunological markersProvided funding becomes available
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Experimental: Early measles vaccine
An additional measles vaccine at 4 months of age, at least 28 days after the third dose of pentavalent vaccine
Biological: Early measles vaccine
Standard Edmonston-Zagreb measles vaccine
No Intervention: Control
Follows the normal vaccination schedule
Please refer to this study by its ClinicalTrials.gov identifier: NCT01644721
|Contact: Cesario Martins, MD, PhDemail@example.com|
|Contact: Amabelia Rodrigues, PhDfirstname.lastname@example.org|
|Bandim Health Project||Recruiting|
|Contact: Cesario Martins, MD, PhD email@example.com|
|Contact: Amabelia Rodrigues, PhD firstname.lastname@example.org|
|Principal Investigator:||Cesario Martins, MD,PhD||Bandim Health Project|
|Principal Investigator:||Amabelia Rodrigues, DMSc||Bandim Health Project|
|Study Director:||Peter Aaby, DMSc||Bandim Health Project|