Trial of Additional Measles Vaccine to Reduce Child Mortality

Measles Vaccine Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01644721
• Other study ID #: OPTIMUNISE_BHP_early MV
• Status: Recruiting
• Phase: Phase 4
• First received: July 17, 2012
• Last updated: August 6, 2014
• Start date: July 2012
• Est. completion date: May 2016

Study information

• Verified date: August 2014
• Source: Bandim Health Project
• Contact: Cesario Martins, MD, PhD
• Email: c.martins[@]bandim.org
• Is FDA regulated: No
• Health authority: Guinea-Bissau: Ministry of HealthDenmark: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3750
• Est. completion date: May 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Months to 6 Months

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Measles
• Measles Vaccine

Intervention

Biological:
• Early measles vaccine
Standard Edmonston-Zagreb measles vaccine

Locations

Country	Name	City	State
Guinea-Bissau	Bandim Health Project	Bissau

Sponsors (5)

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

Country where clinical trial is conducted

Guinea-Bissau, 

References & Publications (1)

Aaby P, Martins CL, Garly ML, Balé 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Immunological markers	Provided funding becomes available
Primary	Mortality	Overall mortality from 4 months to 3 years by sex and age at enrolment	4 months - 3 years	No
Secondary	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	No
Secondary	Morbidity	Hospital admissions, consultations, specific morbidity and measles infection	4 months - 3 years of age	No
Secondary	Growth
Secondary	Antibody titres