Assessing Vaccine Effectiveness of R21/Matrix-M Across Malaria Transmission Settings (AVERT)
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age5-5
SponsorClinton Health Access Initiative Inc.
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
Caregiver is unable or unwilling to provide informed consent.
Severe non-malaria illness at presentation that would interfere with study participation.
Repeat presentation within the protocol-defined exclusion window after a previous enrollment: within 14 days after a microscopy-positive visit; or more than 7 but fewer than 14 days after a microscopy-negative visit. A microscopy-negative visit followed by a positive diagnosis within 7 days will be reclassified as positive rather than treated as a new enrollment.
Documented receipt of any RTS,S malaria vaccine dose.
Trial 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.
Trial design
Design model
Case-control
Time perspective
Prospective
Treatments tested in this trial
R21/Matris-M Malaria vaccine
Biological/VaccineR21/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.
Treatment groups
20,000 Participants
are divided into 2 treatment groupsGroup A: Suspected malaria cases that test positive using microscopy1 intervention
Group B: Suspected malaria cases that test negative using microscopy1 intervention
Trial outcomes
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.
Time frame
At the enrollment illness episode, during the approximately 7- to 8-month study recruitment periodSecondary outcomes
1
Effectiveness of R21/Matrix-M by time since vaccination
Adjusted vaccine effectiveness will be estimated by categorical and/or continuous time since the most recent eligible vaccine dose, including interactions between dose and time.
Time frame
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period2
Effect modification of vaccine effectiveness by malaria transmission intensity
Dose-specific vaccine effectiveness will be compared across prespecified malaria transmission levels within each country.
Time frame
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period3
Effect modification of vaccine effectiveness by sex
Dose-specific vaccine effectiveness will be estimated using vaccination-by-sex interaction terms and sex-stratified analyses.
Time frame
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period4
Effect modification by other malaria prevention interventions
Dose-specific vaccine effectiveness will be assessed in relation to seasonal malaria chemoprevention, insecticide-treated net use, and indoor residual spraying using interaction analyses.
Time frame
At the enrollment illness episode, during the approximately 7- to 8-month recruitment periodSponsors and contacts
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Clinton Health Access Initiative Inc.
Lead sponsor
University of California, San Francisco
Collaborator
Infectious Diseases Research Collaboration, Uganda
Collaborator
Institut de Recherche en Sciences de la Sante, Burkina Faso
Collaborator
Ministry of Health, Burkina Faso
Collaborator
Ministry of Health, Uganda
Collaborator
Source ClinicalTrials.gov