MalariaAVERTNCT07749911
Assessing Vaccine Effectiveness of R21/Matrix-M Across Malaria Transmission Settings (AVERT)
An observational study of Malaria and PLASMODIUM FALCIPARUM MALARIA, run by Clinton Health Access Initiative Inc. at 21 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 months to 5 years
- Conditions the study is for
- Malaria, PLASMODIUM FALCIPARUM MALARIA
- What is being tested?
- R21/Matris-M Malaria vaccine
- Type of treatment
- Vaccines
- How many people
- 20,000 participants
- Where
- 21 sitesin 2 countries
- Study dates
- 14 Jul 2026to Aug 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 months to 5 years
- All sexes
- No healthy volunteers
- Child
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.
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
21 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
21 sites in 2 countries
Burkina Faso12 sites, 12 recruiting
- Recruiting
Boromo urbain 1
Boromo, Boucle Mouhoun
Halidou Tinto, PhD, +226 25 40 92 12, tintoh@crun.bf
- Recruiting
Ouahabou
Boromo, Boucle Mouhoun
h Tinto, PhD, +226 25 40 92 12, tintoh@crun.bf
- Recruiting
Béréba
Houndé, Hauts-Bassins Region
Halidou Tinto, PhD, +226 25 40 92 12, tintoh@crun.bf
- Recruiting
Dohoun
Houndé, Hauts-Bassins Region
Halidou Tinto, PhD, +226 25 40 92 12, tintoh@crun.bf
- Recruiting
Kari
Houndé, Hauts-Bassins Region
Halidou Tinto, +226 25 40 92 12, tintoh@crun.bf
- Recruiting
Déguélin
Karangasso-Vigué, Hauts-Bassins Region
Halidou Tinto, PhD, +226 25 40 92 12, tintoh@crun.bf
- Recruiting
Karangasso-Vigué
Karangasso-Vigué, Hauts-Bassins Region
Halidou Tinto, PhD, +226 25 40 92 12, tintoh@crun.bf
- Recruiting
Sourmousso
Karangasso-Vigué, Hauts-Bassins Region
Halidou Tinto, PhD, +226 25 40 92 12, tintoh@crun.bf
- Recruiting
Wara
Karangasso-Vigué, Hauts-Bassins Region
Halidou Tinto, PhD, +226 25 40 92 12, tintoh@crun.bf
- Recruiting
Mankarga T
Zorgo, Oubri
Halidou Tinto, PhD, +226 25 40 92 12, tintoh@crun.bf
- Recruiting
Mankarga V3
Zorgo, Oubri
Halidou Tinto, PhD, +226 25 40 92 12, tintoh@crun.bf
- Recruiting
Mankarga V6
Zorgo, Oubri
Halidou Tinto, PhD, +226 25 40 92 12, tintoh@crun.bf
Uganda9 sites, 9 recruiting
- Not yet recruiting
Nawaikoke HCIII
Kaliro, Busoga
Joaniter Nankabirwa, MD, PhD, 256 (0) 312 281 479, jnankabirwa@idrc-uganda.org
- Not yet recruiting
Rwenyawawa HCIII
Kikube, Bunyoro
Joaniter Nankabirwa, MD, PhD, 256 (0) 312 281 479, jnankabirwa@idrc-uganda.org
- Not yet recruiting
Kitgum-Matidi HCIII
Kitgum, Acholi
Joaniter Nankabirwa, MD, PhD, 256 (0) 312 281 479, jnankabirwa@idrc-uganda.org
- Not yet recruiting
Namokora HCIV
Kitgum, Acholi
Joaniter Nankabirwa, MD, PhD, 256 (0) 312 281 479, jnankabirwa@idrc-uganda.org
- Not yet recruiting
Kigandalo HCIV
Mayuge, Busoga
Joaniter Nankabirwa, MD, PhD, 256 (0) 312 281 479, jnankabirwa@idrc-uganda.org
- Not yet recruiting
Nadunget HCIII
Moroto, Karamoja
Joaniter Nankabirwa, MD, PhD, 256 (0) 312 281 479, jnankabirwa@idrc-uganda.org
- Not yet recruiting
Lalogi HCIV
Omoro, Acholi
Joaniter Nankabirwa, MD, PhD, 256 (0) 312 281 479, jnankabirwa@idrc-uganda.org
- Not yet recruiting
Orum HCIV
Otuke, Lango
Joaniter Nankabirwa, MD, PhD, 256 (0) 312 281 479, jnankabirwa@idrc-uganda.org
- Not yet recruiting
Otwal HCIII
Oyam, Lango
Joaniter Nankabirwa, MD, PhD, 256 (0) 312 281 479, jnankabirwa@idrc-uganda.org
About this study
Official title: Real-World Effectiveness of the R21/Matrix-M Malaria Vaccine in Children in Burkina Faso and Uganda
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.
Read the detailed description
R21/Matrix-M has been introduced through national immunization programs, but its effectiveness under routine conditions may differ from efficacy observed in clinical trials because children may receive different numbers of doses, doses may be delayed, protection may wane, and malaria transmission and other prevention measures vary across settings.
AVERT will use a prospective test-negative case-control design at approximately 22 outpatient health facilities in moderate- to high-transmission areas of Burkina Faso and Uganda. Consecutive children younger than 5 years who meet country definitions for suspected malaria, are eligible for R21/Matrix-M vaccination, and have caregiver consent will be enrolled. All participants will undergo malaria testing as part of routine care, with study blood smear microscopy used to assign case or control status. A structured caregiver questionnaire will collect demographic, clinical, residential, socioeconomic, health-care access, and malaria-prevention information. R21/Matrix-M dose number and vaccination dates will be verified primarily from vaccination cards, individual health records, or facility vaccination registers.
Cases and controls will be matched, when feasible, by geographic area and calendar time. Conditional or standard logistic regression will estimate adjusted odds ratios comparing vaccinated and unvaccinated children, and vaccine effectiveness will be calculated as (1 - adjusted odds ratio) x 100%. Analyses will be conducted separately by country and will assess effectiveness by dose, time since vaccination, dose spacing, transmission intensity, sex, and use of seasonal malaria chemoprevention, insecticide-treated nets, and indoor residual spraying. A health-system-perspective economic evaluation will estimate incremental cost per uncomplicated clinical malaria case averted.
- Conditions
- Malaria, PLASMODIUM FALCIPARUM MALARIA
- Being tested
- R21/Matris-M Malaria vaccine
- Keywords
- R21/Matrix-M, Malaria vaccine, Vaccine effectiveness, Test-negative design, Clinical malaria, Children, Burkina Faso, Uganda
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
R21/Matris-M Malaria vaccineBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Biological: R21/Matris-M Malaria vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effect modification of vaccine effectiveness by malaria transmission intensity
Dose-specific vaccine effectiveness will be compared across prespecified malaria transmission levels within each country.
Measured: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effect modification of vaccine effectiveness by sex
Dose-specific vaccine effectiveness will be estimated using vaccination-by-sex interaction terms and sex-stratified analyses.
Measured: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
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.
Measured: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effectiveness according to vaccine dose timing
Among vaccinated children, effectiveness will be compared for on-time and late vaccination and in analyses restricted to doses spaced 3 to 5 weeks apart. A late dose is defined as a dose received at least 2 weeks after the scheduled date.
Measured: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effectiveness of the fourth dose relative to the three-dose primary series
Adjusted vaccine effectiveness of 4 doses compared with 3 doses will be estimated using the odds of microscopy-confirmed malaria.
Measured: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2026
- Study start14 Jul 2026
- Primary completionJun 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 20,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinton Health Access Initiative Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, San Francisco, Infectious Diseases Research Collaboration, Uganda, Institut de Recherche en Sciences de la Sante, Burkina Faso, Ministry of Health, Burkina Faso, Ministry of Health, Uganda
- Responsible party
- Sponsor
- Investigators
- Isabel Rodriguez-Barraquer, MD, PhD, Principal investigator, University of California, San FranciscoHalidou Tinto, PhD, Principal investigator, Institut de Recherche en Sciences de la Santé (Burkina Faso)Joaniter Nankabirwa, MD, PhD, Principal investigator, Infectious Diseases Research Collaboration, Kampala, Uganda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07749911
- Sponsor's protocol ID
- AVERT-2026-01
- Other IDs
- INV-097482, 2026-06-05
- Acronym
- AVERT
- Status last verified
- Aug 2026
- First submitted
- 3 Aug 2026
- Last updated
- 6 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Real-World Effectiveness of the R21/Matrix-M Malaria Vaccine in Children in Burkina Faso and Uganda
- ClinicalTrials.gov ID
- NCT07749911
- Acronym / sponsor ID
- AVERT / AVERT-2026-01
- Conditions
- Malaria, PLASMODIUM FALCIPARUM MALARIA
- Keywords
- R21/Matrix-M, Malaria vaccine, Vaccine effectiveness, Test-negative design, Clinical malaria, Children, Burkina Faso, Uganda
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 20,000 participants (estimated)
- Lead sponsor
- Clinton Health Access Initiative Inc.University, hospital or other
- Collaborators
- University of California, San Francisco, Infectious Diseases Research Collaboration, Uganda, Institut de Recherche en Sciences de la Sante, Burkina Faso, Ministry of Health, Burkina Faso, Ministry of Health, Uganda
- Study start
- 14 Jul 2026 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 6 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
R21/Matrix-M has been introduced through national immunization programs, but its effectiveness under routine conditions may differ from efficacy observed in clinical trials because children may receive different numbers of doses, doses may be delayed, protection may wane, and malaria transmission and other prevention measures vary across settings.
AVERT will use a prospective test-negative case-control design at approximately 22 outpatient health facilities in moderate- to high-transmission areas of Burkina Faso and Uganda. Consecutive children younger than 5 years who meet country definitions for suspected malaria, are eligible for R21/Matrix-M vaccination, and have caregiver consent will be enrolled. All participants will undergo malaria testing as part of routine care, with study blood smear microscopy used to assign case or control status. A structured caregiver questionnaire will collect demographic, clinical, residential, socioeconomic, health-care access, and malaria-prevention information. R21/Matrix-M dose number and vaccination dates will be verified primarily from vaccination cards, individual health records, or facility vaccination registers.
Cases and controls will be matched, when feasible, by geographic area and calendar time. Conditional or standard logistic regression will estimate adjusted odds ratios comparing vaccinated and unvaccinated children, and vaccine effectiveness will be calculated as (1 - adjusted odds ratio) x 100%. Analyses will be conducted separately by country and will assess effectiveness by dose, time since vaccination, dose spacing, transmission intensity, sex, and use of seasonal malaria chemoprevention, insecticide-treated nets, and indoor residual spraying. A health-system-perspective economic evaluation will estimate incremental cost per uncomplicated clinical malaria case averted.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Suspected malaria cases that test positive using microscopy | – | Biological: R21/Matris-M Malaria vaccineEligible children with suspected malaria whose enrollment blood smear microscopy result is positive for P. falciparum infection |
| Suspected malaria cases that test negative using microscopy | – | Biological: R21/Matris-M Malaria vaccineEligible children with suspected malaria whose enrollment blood smear microscopy result is negative for P. falciparum infection |
Who may qualify
- Ages
- 5 months to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| R21/Matris-M Malaria 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. | Biological | Suspected malaria cases that test negative using microscopy, Suspected malaria cases that test positive using microscopy |
Primary outcome
Dose-specific effectiveness of R21/Matrix-M against microscopy-confirmed clinical malaria
Time frame: At the enrollment illness episode, during the approximately 7- to 8-month study recruitment period
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.
6 secondary outcomes
Effectiveness of R21/Matrix-M by time since vaccination
Time frame: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effect modification of vaccine effectiveness by malaria transmission intensity
Time frame: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effect modification of vaccine effectiveness by sex
Time frame: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effect modification by other malaria prevention interventions
Time frame: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effectiveness according to vaccine dose timing
Time frame: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effectiveness of the fourth dose relative to the three-dose primary series
Time frame: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Isabel Rodriguez-Barraquer, MD, PhD principal investigator
University of California, San Francisco
Halidou Tinto, PhD principal investigator
Institut de Recherche en Sciences de la Santé (Burkina Faso)
Joaniter Nankabirwa, MD, PhD principal investigator
Infectious Diseases Research Collaboration, Kampala, Uganda
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malaria and PLASMODIUM FALCIPARUM MALARIA, run by Clinton Health Access Initiative Inc. at 21 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Burkina Faso, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-specific effectiveness of R21/Matrix-M against microscopy-confirmed clinical malaria (time frame: At the enrollment illness episode, during the approximately 7- to 8-month study recruitment period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026.