NCT01644721

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3,750

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jul 2012

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2012

Completed
16 days until next milestone

First Submitted

Initial submission to the registry

July 17, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 19, 2012

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2016

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2016

Completed
Last Updated

February 11, 2026

Status Verified

February 1, 2026

Enrollment Period

3.9 years

First QC Date

July 17, 2012

Last Update Submit

February 9, 2026

Conditions

Measles Vaccine

Keywords

Child mortalityMeasles vaccineNon-specific effects

Outcome Measures

Primary Outcomes (1)

  • Mortality

    Overall mortality from 4 months to 3 years by sex and age at enrolment

    4 months - 3 years

Secondary Outcomes (4)

  • Mortality

    4 to 9 months of age and from 9 months to 3 years of age

  • Morbidity

    4 months - 3 years of age

  • Growth

  • Antibody titres

Other Outcomes (1)

  • Immunological markers

Study Arms (2)

Early measles vaccine

EXPERIMENTAL

An additional measles vaccine at 4 months of age, at least 28 days after the third dose of pentavalent vaccine

Biological: Early measles vaccine

Control

NO INTERVENTION

Follows the normal vaccination schedule

Interventions

Early measles vaccineBIOLOGICAL

Standard Edmonston-Zagreb measles vaccine

Early measles vaccine

Eligibility Criteria

Age4 Months - 6 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Bandim Health Project

Bissau, Guinea-Bissau

Location

Related Publications (4)

  • 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.

    PMID: 21118875BACKGROUND

  • Steiniche MM, Thysen SM, Jensen AKG, Rodrigues A, Martins C, Meyrowitsch DW, Aaby P, Fisker AB. The effect of early measles vaccination on morbidity and growth: A randomised trial from Guinea-Bissau. Vaccine. 2020 Mar 4;38(11):2487-2494. doi: 10.1016/j.vaccine.2020.01.096. Epub 2020 Feb 13.

    PMID: 32061387RESULT

  • Fisker AB, Nebie E, Schoeps A, Martins C, Rodrigues A, Zakane A, Kagone M, Byberg S, Thysen SM, Tiendrebeogo J, Coulibaly B, Sankoh O, Becher H, Whittle HC, van der Klis FRM, Benn CS, Sie A, Muller O, Aaby P. A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine: Effects on Mortality and Measles Antibody Levels. Clin Infect Dis. 2018 May 2;66(10):1573-1580. doi: 10.1093/cid/cix1033.

    PMID: 29177407RESULT

  • Schoeps A, Nebie E, Fisker AB, Sie A, Zakane A, Muller O, Aaby P, Becher H. No effect of an additional early dose of measles vaccine on hospitalization or mortality in children: A randomized controlled trial. Vaccine. 2018 Apr 5;36(15):1965-1971. doi: 10.1016/j.vaccine.2018.02.104. Epub 2018 Mar 6.

    PMID: 29523450DERIVED

Study Officials

  • Cesario Martins, MD,PhD

    Bandim Health Project

    PRINCIPAL INVESTIGATOR

  • Amabelia Rodrigues, DMSc

    Bandim Health Project

    PRINCIPAL INVESTIGATOR

  • Peter Aaby, DMSc

    Bandim Health Project

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 17, 2012

First Posted

July 19, 2012

Study Start

July 1, 2012

Primary Completion

June 1, 2016

Study Completion

October 1, 2016

Last Updated

February 11, 2026

Record last verified: 2026-02

Locations

GU(1)