Trial of Additional Measles Vaccine to Reduce Child Mortality

Summary

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.

Conditions

• Measles Vaccine

Interventions

BIOLOGICAL

Early measles vaccine

Standard Edmonston-Zagreb measles vaccine

Sponsors & Collaborators

• Centre de Recherche en Sante de Nouna, Burkina Faso

  collaborator OTHER_GOV

• Navrongo Health Research Centre, Ghana

  collaborator OTHER

• Heidelberg University

  collaborator OTHER

• National Institute for Public Health and the Environment, RIVM, Holland

  collaborator UNKNOWN

• Bandim Health Project

  lead OTHER

Principal Investigators

• Cesario Martins, MD,PhD · Bandim Health Project

• Amabelia Rodrigues, DMSc · Bandim Health Project

• Peter Aaby, DMSc · Bandim Health Project

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

4 Months

Max Age

6 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-07-31

Primary Completion

2016-06-30

Completion

2016-10-31

Countries

• Guinea-Bissau

Study Locations