Trial of Additional Measles Vaccine to Reduce Child Mortality. Burkina Faso.

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

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 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, Burkina Faso: Newborns are followed through the Health and Demographic Surveillance System (HDSS) of the Centre de Recherche en Sante de Nouna. 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 43% reduction in overall mortality at each site the investigators intend to enroll at least 4050 children in Burkina Faso. 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 Overview

• Status: Unknown
• Conditions: Measles Vaccine
• Intervention / Treatment: Biological: Early measles vaccine

• Study Type: Interventional
• Enrollment (Anticipated): 4050
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ali Sié, MD; Phone Number: +22620537043; Email: alisie.crsn@fasonet.bf
• Study Contact Backup: Name: Maurice Yé, MD; Phone Number: +22670244811; Email: yemaure@yahoo.fr

Study Locations

• Burkina Faso
  • Nouna, Burkina Faso
    • Recruiting
    • Centre de recherche en Santé de nouna
    • Contact: Ali Sie, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 6 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Control
EXPERIMENTAL: Early measles vaccine; The intervention is about to administer an early standard dose of Edmonston-Zagreb (EZ) measles vaccine in addition to the conventional dose. As such children will be randomised to receive either an early measles vaccine at 4 months after DTP3 or not. Thereafter both groups of children will receive the recommended EZ measles vaccine at 9 months of age according to WHO policy.	Biological: Early measles vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mortality	4 months - 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality	4 to 9 months of age and from 9 months to 3 years of age
Morbidity	4 months - 3 years of age
Growth	4 months to 3 years of age
Antibody titres	9 months to 3 years of age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological markers	Provided funding becomes available	9 months to 3 years of age

Collaborators and Investigators

• Sponsor: Bandim Health Project
• Collaborators: Heidelberg University; Centre de Recherche en Sante de Nouna, Burkina Faso; Navrongo Health Research Centre, Ghana; National Institute for Public Health and the Environment, RIVM, Holland

Publications and helpful links

General Publications

• Aaby P, Martins CL, Garly ML, Bale C, Andersen A, Rodrigues A, Ravn H, Lisse IM, Benn CS, Whittle HC. Non-specific effects of standard measles vaccine at 4.5 and 9 months of age on childhood mortality: randomised controlled trial. BMJ. 2010 Nov 30;341:c6495. doi: 10.1136/bmj.c6495.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ANTICIPATED): December 1, 2015
• Study Completion (ANTICIPATED): March 1, 2016

Study Registration Dates

• First Submitted: August 16, 2012
• First Submitted That Met QC Criteria: August 16, 2012
• First Posted (ESTIMATE): August 20, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): August 7, 2014
• Last Update Submitted That Met QC Criteria: August 6, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Measles vaccine; Non-specific effects; Child mortality
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; Measles
• Other Study ID Numbers: OPTIMUNISE_NOUNA_early MV