Clinical trial NCT01644721: Trial of Additional Measles Vaccine to Reduce Child Mortality
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Measles Vaccine
Keywords: Child mortality
Measles vaccine
Non-specific effects
Lead sponsor: Bandim Health Project
Sponsor class: OTHER
Collaborators: name: Centre de Recherche en Sante de Nouna, Burkina Faso
name: Navrongo Health Research Centre, Ghana
name: Heidelberg University
name: National Institute for Public Health and the Environment, RIVM, Holland
First posted: 2012-07-19
Enrollment: 3750
Sex: ALL
Minimum age (years): 4
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Mortality
timeFrame: 4 months - 3 years
Secondary outcomes:
measure: Mortality
timeFrame: 4 to 9 months of age and from 9 months to 3 years of age
measure: Morbidity
timeFrame: 4 months - 3 years of age
measure: Growth
measure: Antibody titres
Other outcomes:
measure: Immunological markers
Locations:
city: Bissau
country: Guinea-Bissau
facility: Bandim Health Project
Study officials:
affiliation: Bandim Health Project
name: Cesario Martins, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bandim Health Project
name: Amabelia Rodrigues, DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Bandim Health Project
name: Peter Aaby, DMSc
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.