NCT07749911

Brief Summary

The AVERT study is a prospective observational test-negative case control study evaluating the real-world effectiveness of the R21/Matrix-M malaria vaccine among children younger than 5 years in Burkina Faso and Uganda. Children who seek outpatient care with suspected malaria and are eligible for the national R21/Matrix-M vaccination program will be enrolled. Malaria infection will be determined by blood smear microscopy. Children with a positive microscopy result will be classified as cases and children with a negative result as controls. Vaccination history, including the number and timing of doses, will be obtained primarily from vaccination cards or other written records. Vaccine effectiveness will be estimated by comparing the odds of vaccination among cases and controls.

Trial Health

80
On Track

Trial Health Score

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

Enrollment
20,000

participants targeted

Target at P75+ for all trials

Timeline
12mo left

Started Jul 2026

Geographic Reach
2 countries

21 active sites

Status
recruiting

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

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress6%
Jul 2026Aug 2027

Study Start

First participant enrolled

July 14, 2026

Completed
20 days until next milestone

First Submitted

Initial submission to the registry

August 3, 2026

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 6, 2026

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2027

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2027

Last Updated

August 6, 2026

Status Verified

August 1, 2026

Enrollment Period

11 months

First QC Date

August 3, 2026

Last Update Submit

August 3, 2026

Conditions

Keywords

R21/Matrix-MMalaria vaccineVaccine effectivenessTest-negative designClinical malariaChildrenBurkina FasoUganda

Outcome Measures

Primary Outcomes (1)

  • Dose-specific effectiveness of R21/Matrix-M against microscopy-confirmed clinical malaria

    Adjusted vaccine effectiveness will be calculated as (1 - adjusted odds ratio) x 100%. The odds ratio will compare the odds of each documented R21/Matrix-M dose category among microscopy-positive malaria cases with the odds among microscopy-negative controls, using children with 0 doses as the primary reference group. Prespecified grouped dose categories will be used if individual dose categories do not have adequate statistical power.

    At the enrollment illness episode, during the approximately 7- to 8-month study recruitment period

Secondary Outcomes (6)

  • Effectiveness of R21/Matrix-M by time since vaccination

    At the enrollment illness episode, during the approximately 7- to 8-month recruitment period

  • Effect modification of vaccine effectiveness by malaria transmission intensity

    At the enrollment illness episode, during the approximately 7- to 8-month recruitment period

  • Effect modification of vaccine effectiveness by sex

    At the enrollment illness episode, during the approximately 7- to 8-month recruitment period

  • Effect modification by other malaria prevention interventions

    At the enrollment illness episode, during the approximately 7- to 8-month recruitment period

  • Effectiveness according to vaccine dose timing

    At the enrollment illness episode, during the approximately 7- to 8-month recruitment period

  • +1 more secondary outcomes

Study Arms (2)

Suspected malaria cases that test positive using microscopy

Eligible children with suspected malaria whose enrollment blood smear microscopy result is positive for P. falciparum infection

Biological: R21/Matris-M Malaria vaccine

Suspected malaria cases that test negative using microscopy

Eligible children with suspected malaria whose enrollment blood smear microscopy result is negative for P. falciparum infection

Biological: R21/Matris-M Malaria vaccine

Interventions

R21/Matrix-M vaccination received through routine national immunization programs. The study will record the number and dates of doses received. Children will be classified as having received 0, 1, 2, 3, or 4 eligible doses, with prespecified grouped classifications used if individual dose categories are underpowered. Doses given fewer than 14 days before malaria testing will not count toward the primary exposure classification.

Suspected malaria cases that test negative using microscopySuspected malaria cases that test positive using microscopy

Eligibility Criteria

Age5 Months - 5 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)
Sampling MethodNon-Probability Sample
Study Population

Children younger than 5 years who reside in the catchment areas of selected health facilities in R21/Matrix-M implementation districts in Burkina Faso or Uganda, are age-eligible for vaccination under the relevant national schedule, and present for outpatient care with suspected malaria. Participants are recruited from health facilities in moderate- to high-transmission settings.

You may qualify if:

  • Residence in an area where R21/Matrix-M is implemented and within the catchment area of a selected study facility.
  • Younger than 5 years and eligibleto receive R21/Matrix-M under the national vaccination schedule at rollout.
  • Meets the country definition of suspected malaria, generally axillary temperature of at least 37.5 degrees Celsius or a history of fever within the previous 24 hours, and is undergoing malaria testing.
  • Written informed consent provided by an adult caregiver aged 18 years or older.

You may not qualify if:

  • Caregiver is unable or unwilling to provide informed consent.
  • Severe non-malaria illness at presentation that would interfere with study participation.
  • Documented receipt of any RTS,S malaria vaccine dose.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

Boromo urbain 1

Boromo, Boucle Mouhoun, Burkina Faso

RECRUITING

Ouahabou

Boromo, Boucle Mouhoun, Burkina Faso

RECRUITING

Béréba

Houndé, Hauts-Bassins Region, Burkina Faso

RECRUITING

Dohoun

Houndé, Hauts-Bassins Region, Burkina Faso

RECRUITING

Kari

Houndé, Hauts-Bassins Region, Burkina Faso

RECRUITING

Déguélin

Karangasso-Vigué, Hauts-Bassins Region, Burkina Faso

RECRUITING

Karangasso-Vigué

Karangasso-Vigué, Hauts-Bassins Region, Burkina Faso

RECRUITING

Sourmousso

Karangasso-Vigué, Hauts-Bassins Region, Burkina Faso

RECRUITING

Wara

Karangasso-Vigué, Hauts-Bassins Region, Burkina Faso

RECRUITING

Mankarga T

Zorgo, Oubri, Burkina Faso

RECRUITING

Mankarga V3

Zorgo, Oubri, Burkina Faso

RECRUITING

Mankarga V6

Zorgo, Oubri, Burkina Faso

RECRUITING

Kitgum-Matidi HCIII

Kitgum, Acholi, Uganda

NOT YET RECRUITING

Namokora HCIV

Kitgum, Acholi, Uganda

NOT YET RECRUITING

Lalogi HCIV

Omoro, Acholi, Uganda

NOT YET RECRUITING

Rwenyawawa HCIII

Kikube, Bunyoro, Uganda

NOT YET RECRUITING

Nawaikoke HCIII

Kaliro, Busoga, Uganda

NOT YET RECRUITING

Kigandalo HCIV

Mayuge, Busoga, Uganda

NOT YET RECRUITING

Nadunget HCIII

Moroto, Karamoja, Uganda

NOT YET RECRUITING

Orum HCIV

Otuke, Lango, Uganda

NOT YET RECRUITING

Otwal HCIII

Oyam, Lango, Uganda

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Finger-prick dried blood spots, blood smears, and used positive malaria rapid diagnostic tests will be collected. Blood smears will confirm case or control status, and specimens may undergo serology. Malaria-positive specimens may undergo parasite genotyping. Samples may be stored for future ethically approved research where separate consent and local approvals permit.

MeSH Terms

Conditions

MalariaMalaria, Falciparum

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Study Officials

  • Isabel Rodriguez-Barraquer, MD, PhD

    University of California, San Francisco

    PRINCIPAL INVESTIGATOR
  • Halidou Tinto, PhD

    Institut de Recherche en Sciences de la Santé (Burkina Faso)

    PRINCIPAL INVESTIGATOR
  • Joaniter Nankabirwa, MD, PhD

    Infectious Diseases Research Collaboration, Kampala, Uganda

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 3, 2026

First Posted

August 6, 2026

Study Start

July 14, 2026

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

August 1, 2027

Last Updated

August 6, 2026

Record last verified: 2026-08

Locations