Increasing Measles Vaccination Coverage Through Supplementation With an SQ-LNS Incentive in Children Aged 6-23 Months

NutriVax-Measles: Increasing Measles Vaccination Coverage Through Supplementation With an SQ-LNS Incentive in Children Aged 6-23 Months, a Pragmatic Parallel Cluster-randomized Controlled Trial in Yobe State, Northern Nigeria

Provision of SQ-LNS also holds promise in incentivizing vaccination as well as other health services.

The investigators will estimate 1) the effectiveness of a SQ-LNS mass supplementation program added to routine immunization program compared to routine immunization program alone in terms of measles vaccine coverage, after 12 months of program implementation, 1) in children aged 12-23 months in the end line cross-sectional household survey, 2) in children aged 6-12 months at inclusion, in a longitudinal 12 months follow-up survey.

Secondary objectives are to assess the barriers and facilitators from the perspectives of parents/legal guardian of children, health care providers and community health workers and to assess the cost-efficiency of the

This study will be implemented in 20 wards covering the Karasuwa and Nguru Local Government Areas (LGAs) in Yobe state, Northeast Nigeria.

This is a pragmatic parallel cluster randomized trial (PCT) with baseline measure with different populations and data collection modes: 1) baseline and end line cross-sectional household surveys of children aged 12-23 months, 2) a longitudinal follow-up survey (LS) of children aged 6-12 months at inclusion, 3) a qualitative feasibility and acceptability survey of parents of children aged 6-23 months, of health providers, of community health workers and community representatives and 4) a cost survey of parents/legal guardian of children from the longitudinal follow-up cohort, and 5) a health facility cost survey of a randomized subsample of health facilities.

Clusters will be randomly allocated at a ratio of 1:1 either to the standard arm or to the NutriVax arm:

• The standard Expanded Program on Immunization (EPI) in children aged 6-23 months delivered according to the Ministry of Health's routine plans in the community and at health centres and health posts, named the standard EPI arm;
• The NutriVax program combining the EPI in children aged 6-23 months according to the Ministry of Health's routine plans in the community and at health centres (i.e. PHCCs) and health posts associated with SQ-LNS mass supplementation integrated into pre-existing services delivered at health centres (i.e. PHCCs) for children 6-23 months of age, named the NutriVax arm.

Study Overview

• Status: Not yet recruiting
• Conditions: Nutrition; Vaccination; Immunization Coverage
• Intervention / Treatment: Dietary supplement: Small-quantity lipid-based nutrition supplements (SQ-LNS) NutriVax

Detailed Description

Background/ Rational

Every year, hundreds of thousands of children are treated for severe wasting while experiencing repeated and prolonged outbreaks of vaccine-preventable illnesses, most notably measles. At least 20 million children annually still do not receive immunizations. Northeast Nigeria is at the epicentre of this dynamic, recording some of the worst malnutrition indicators and lowest vaccination coverage rates in the world.

Small-quantity lipid-based nutrient supplements (SQ-LNS) are a class of ready-to-use food supplements which are highly nutrient-dense and fortified designed for preventing malnutrition and improving child survival, growth, and development. A recent meta-analysis on SQ-LNS reveals that feeding a child just one sachet of SQ-LNS a day for a year can reduce their risk of mortality by 27%, and reduce cases of severe wasting by 31% and severe stunting by 17%. The overall strength of evidence on SQ-LNS benefits led the authors of a 2021 Lancet review to call scaling-up SQ-LNS a priority action.

Provision of SQ-LNS also holds promise in incentivizing vaccination as well as other health services.

Primary objective

To estimate the effectiveness of a SQ-LNS mass supplementation program added to routine immunization program compared to routine immunization program alone in terms of measles vaccine coverage, after 12 months of program implementation, in children aged 12-23 months in the end line cross-sectional household survey.

Main secondary objective

To estimate the effectiveness of a SQ-LNS mass supplementation program added to routine immunization program compared to routine immunization program alone in terms of measles vaccine coverage, after 12 months of program implementation, in children aged 6-12 months at inclusion in the longitudinal 12 months follow-up survey.

Secondary objectives

• To estimate the effectiveness of a SQ-LNS mass supplementation program added to routine immunization program compared to routine immunization program alone in children aged 6-23 months, after 12 months of program implementation, in terms of 1) all other infant vaccines' uptake, 2) timeliness of age-eligible vaccinations; 3) anthropometric status, 4) uptake of paediatric curative and preventive health consultations and activities.
• To assess the barriers and facilitators to SQ-LNS mass supplementation implemented as part of a routine immunization program in health facilities, from the perspectives of parents/legal guardian of children aged 6-23 months, health care providers and community health workers.
• To assess the cost-efficiency of a SQ-LNS mass supplementation program compared to routine immunization program in terms of cost per child supplemented and vaccinated.

Study sites : 20 wards covering the Karasuwa and Nguru Local Government Areas (LGAs) in Yobe state, Northeast Nigeria

Study design

A pragmatic parallel cluster randomized trial (PCT) with baseline measure with different populations and data collection modes: 1) baseline and end line cross-sectional household surveys of children aged 12-23 months, 2) a longitudinal follow-up survey (LS) of children aged 6-12 months at inclusion, 3) a qualitative feasibility and acceptability survey of parents of children aged 6-23 months, of health providers, of community health workers and community representatives and 4) a cost survey of parents/legal guardian of children from the longitudinal follow-up cohort, and 5) a health facility cost survey of a randomized subsample of health facilities.

Interventions compared

1. The standard Expanded Program on Immunization (EPI) in children aged 6-23 months delivered according to the Ministry of Health's routine plans in the community and at health centres and health posts, named the standard EPI arm.
2. The NutriVax program combining the EPI in children aged 6-23 months according to the Ministry of Health's routine plans in the community and at health centres (i.e. PHCCs) and health posts associated with SQ-LNS mass supplementation integrated into pre-existing services delivered at health centres (i.e. PHCCs) for children 6-23 months of age, named the NutriVax arm.

The unit of randomization (cluster) will be the ward and its catchment area. Clusters will be randomly allocated at a ratio of 1:1 either to the standard EPI arm or to the NutriVax arm.

Statistical analyses

Differences in measles vaccine coverage (dose 1) between control and intervention arms at end line will be assessed using multilevel regression models.

The study will be conducted in compliance with the protocol, the Declaration of Helsinki, the GCP guidelines and the Nigerian National Code for Health Research Ethics

Timeline : 2 years (December 2023-December 2025)

• Study Type: Interventional
• Enrollment (Estimated): 3720
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cécile Cazes, PhD; Phone Number: +33 7 80 58 97 42; Email: cecile.cazes@coral.alima.ngo
• Study Contact Backup: Name: Kevin Phelan, MSc; Email: kevin.phelan@alima.ngo

Study Locations

• Nigeria
  • Yobe
    • Damaturu, Yobe, Nigeria
      • Yobe State University Teaching Hospital
      • Contact: Baba Goni Waru, Dr; Email: babawaru@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

• Baseline and endline cross-sectional household surveys Inclusion criteria

  • Aged 12-23 months;
  • With oral informed consent of parent or legal guardian;
  • Residing in the catchment settlements of wards included in the study. Exclusion criteria
  • Included in the longitudinal follow-up.

• Longitudinal follow-up survey Inclusion criteria

  • Aged 6-12 months;
  • With written informed consent of parent or legal guardian;
  • Residing in the catchment settlements of wards included in the study. Exclusion criteria
  • Acute malnutrition criteria as per the WHO definition (i.e. MUAC< 125 or WHZ < -2 or nutritional edema);
  • - Known medical complication that requires referral for hospitalization;
  • Known allergies to SQ-LNS or SQ-LNS contraindication;
  • Any other condition interfering with protocol adherence or the ability to give informed consent, in the judgment of the Field Investigator Sampling for HHS and LS will be carried out in three stages in each LGA using probability proportional to size (PPS).

• Qualitative feasibility and acceptability survey Inclusion

  • Parent or legal guardian of a child aged 6-23 months and residing in the catchment settlements of wards included in the study, or Health worker of the ministry of health involved in the study,or Community representative or Community health workers;
  • With written informed consent. Exclusion criteria
  • None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard Expanded program on immunization; The standard Expanded Program on Immunization (EPI) in children aged 6-23 months delivered according to the Ministry of Health's routine plans in the community and at health centres and health posts.
Experimental: NutriVax; The NutriVax strategy combines the EPI in children aged 6-23 months according to the Ministry of Health's routine plans in the community and at health centres and health posts associated with SQ-LNS mass supplementation integrated into pre-existing services delivered at health centres for children 6-23 months of age.	Dietary supplement: Small-quantity lipid-based nutrition supplements (SQ-LNS) NutriVax; The intervention tested combines the delivery of the Expanded Program on Immunization (EPI) in children aged 6-23 months according to the Ministry of Health's routine plans in the community and at health centres associated with SQ-LNS mass supplementation integrated into pre-existing services delivered at health centres for children 6-23 months of age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measles vaccine coverage in children aged 12-23 months	The proportion of children aged 12-23 months in the endline survey who have received at least one dose of measles vaccine, as reported on their vaccination card.	Measured after one year after of intervention implementation.
Measles vaccine coverage in children 6-12 months at inclusion	The proportion of children aged 6-12 months at inclusion in the longitudinal follow-up survey, who have received at least one additional dose of measles vaccine, as reported on their vaccination card, administered between inclusion and the end of follow-up.	Measured after one year after of intervention implementation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measles vaccine coverage: at least one dose	The proportion of children with at least one measles vaccine as reported on a vaccination card or by recall.	Measured after one year after of intervention implementation.
Measles vaccine coverage : two doses	The proportion of children with a measles 2 vaccine as reported on a vaccination card or by recall	Measured after one year after of intervention implementation.
Timeliness of measles 1 vaccination	Proportion of children with Measles 1 vaccine received within 30 days of turning 9 months by card	Measured after one year after of intervention implementation.
Other infant vaccines coverage	Proportion of children with Pentavalent 1 and 3, yellow fever, meningitis vaccine as reported on a vaccination card or by recall	Measured after one year after of intervention implementation.
Zero-dose	Proportion of children with No measles + pentavalent + yellow fever + meningitis vaccines reported on a vaccination card or by recall.	Measured after one year after of intervention implementation.
Fully immunization	Proportion of children who had received all childhood vaccinations recommended by the Nigeria MOH.	Measured after one year after of intervention implementation.
Acceptability	Barriers and facilitators to access health care centres and receive SQ-LNS mass supplementation implemented as a routine preventive program nested in health facilities activities	Measured after 2 months and one year after of intervention implementation.
Cost-efficiency	• Cost per child vaccinated and supplemented compared to cost per child vaccinated only, using a facility and caregiver perspectiveto identify all provider and caregiver costs associated with treatment.	Measured after one year after of intervention implementation.

Collaborators and Investigators

• Sponsor: Alliance for International Medical Action
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Programme PAC-CI, Site ANRS-MIE de Côte d'Ivoire; Gavi, The Vaccine Alliance; Eleanor Crook Foundation; Yobe State Ministry of Health, Nigeria
• Investigators: Principal Investigator: Renaud Becquet, PhD, Institut National de la Santé Et de la Recherche Médicale, France

Publications and helpful links

Helpful Links

• Why ECF and Gavi are joining forces to explore pairing nutritional supplement and vaccine delivery to save more lives

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): June 15, 2025
• Study Completion (Estimated): June 15, 2025

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Child; Cost-effectiveness; Africa; Measles; Acceptability; Nigeria; Incentives; Vaccination coverage; Small quantity of Lipid Based Nutrients (SQ-LNS); Malnutrition, prevention
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; Measles
• Other Study ID Numbers: NutriVax-Measles

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Possible data sharing agreement, possible one year after publication of the main results.
• IPD Sharing Time Frame: Before (protocol, ICF) and during data collection (SAP)
• IPD Sharing Access Criteria: Protocol, ICF and SAP on clinicaltrials.gov
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No