Cette page a été traduite automatiquement et l'exactitude de la traduction n'est pas garantie. Veuillez vous référer au version anglaise pour un texte source.

Assessing Vaccine Effectiveness of R21/Matrix-M Across Malaria Transmission Settings (AVERT) (AVERT)

3 août 2026 mis à jour par: Clinton Health Access Initiative Inc.

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.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Observationnel

Inscription (Estimé)

20000

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Burkina Faso
    • Boucle Mouhoun
      • Boromo, Boucle Mouhoun, Burkina Faso
        • Recrutement
        • Boromo urbain 1
        • Contact:
          • Halidou Tinto, PhD
          • Numéro de téléphone: +226 25 40 92 12
          • E-mail: tintoh@crun.bf
      • Boromo, Boucle Mouhoun, Burkina Faso
        • Recrutement
        • Ouahabou
        • Contact:
          • h Tinto, PhD
          • Numéro de téléphone: +226 25 40 92 12
          • E-mail: tintoh@crun.bf
    • Hauts-Bassins Region
      • Houndé, Hauts-Bassins Region, Burkina Faso
        • Recrutement
        • Béréba
        • Contact:
          • Halidou Tinto, PhD
          • Numéro de téléphone: +226 25 40 92 12
          • E-mail: tintoh@crun.bf
      • Houndé, Hauts-Bassins Region, Burkina Faso
        • Recrutement
        • Dohoun
        • Contact:
          • Halidou Tinto, PhD
          • Numéro de téléphone: +226 25 40 92 12
          • E-mail: tintoh@crun.bf
      • Houndé, Hauts-Bassins Region, Burkina Faso
        • Recrutement
        • Kari
        • Contact:
          • Halidou Tinto
          • Numéro de téléphone: +226 25 40 92 12
          • E-mail: tintoh@crun.bf
      • Karangasso-Vigué, Hauts-Bassins Region, Burkina Faso
        • Recrutement
        • Déguélin
        • Contact:
          • Halidou Tinto, PhD
          • Numéro de téléphone: +226 25 40 92 12
          • E-mail: tintoh@crun.bf
      • Karangasso-Vigué, Hauts-Bassins Region, Burkina Faso
        • Recrutement
        • Karangasso-Vigué
        • Contact:
          • Halidou Tinto, PhD
          • Numéro de téléphone: +226 25 40 92 12
          • E-mail: tintoh@crun.bf
      • Karangasso-Vigué, Hauts-Bassins Region, Burkina Faso
        • Recrutement
        • Sourmousso
        • Contact:
          • Halidou Tinto, PhD
          • Numéro de téléphone: +226 25 40 92 12
          • E-mail: tintoh@crun.bf
      • Karangasso-Vigué, Hauts-Bassins Region, Burkina Faso
        • Recrutement
        • Wara
        • Contact:
          • Halidou Tinto, PhD
          • Numéro de téléphone: +226 25 40 92 12
          • E-mail: tintoh@crun.bf
    • Oubri
      • Zorgo, Oubri, Burkina Faso
        • Recrutement
        • Mankarga T
        • Contact:
          • Halidou Tinto, PhD
          • Numéro de téléphone: +226 25 40 92 12
          • E-mail: tintoh@crun.bf
      • Zorgo, Oubri, Burkina Faso
        • Recrutement
        • Mankarga V3
        • Contact:
          • Halidou Tinto, PhD
          • Numéro de téléphone: +226 25 40 92 12
          • E-mail: tintoh@crun.bf
      • Zorgo, Oubri, Burkina Faso
        • Recrutement
        • Mankarga V6
        • Contact:
          • Halidou Tinto, PhD
          • Numéro de téléphone: +226 25 40 92 12
          • E-mail: tintoh@crun.bf
  • Ouganda
    • Acholi
      • Kitgum, Acholi, Ouganda
        • Pas encore de recrutement
        • Kitgum-Matidi HCIII
        • Contact:
      • Kitgum, Acholi, Ouganda
        • Pas encore de recrutement
        • Namokora HCIV
        • Contact:
      • Omoro, Acholi, Ouganda
        • Pas encore de recrutement
        • Lalogi HCIV
        • Contact:
    • Bunyoro
      • Kikube, Bunyoro, Ouganda
        • Pas encore de recrutement
        • Rwenyawawa HCIII
        • Contact:
    • Busoga
      • Kaliro, Busoga, Ouganda
        • Pas encore de recrutement
        • Nawaikoke HCIII
        • Contact:
      • Mayuge, Busoga, Ouganda
        • Pas encore de recrutement
        • Kigandalo HCIV
        • Contact:
    • Karamoja
      • Moroto, Karamoja, Ouganda
        • Pas encore de recrutement
        • Nadunget HCIII
        • Contact:
    • Lango
      • Otuke, Lango, Ouganda
        • Pas encore de recrutement
        • Orum HCIV
        • Contact:
      • Oyam, Lango, Ouganda
        • Pas encore de recrutement
        • Otwal HCIII
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Enfant

Accepte les volontaires sains

Non

Méthode d'échantillonnage

Échantillon non probabiliste

Population étudiée

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.

La description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

Cohortes et interventions

Groupe / Cohorte
Intervention / Traitement
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
Biologique: R21/Matris-M Malaria vaccine
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 microscopy
Eligible children with suspected malaria whose enrollment blood smear microscopy result is negative for P. falciparum infection
Biologique: R21/Matris-M Malaria vaccine
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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Dose-specific effectiveness of R21/Matrix-M against microscopy-confirmed clinical malaria
Délai: 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.
At the enrollment illness episode, during the approximately 7- to 8-month study recruitment period

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Effectiveness of R21/Matrix-M by time since vaccination
Délai: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
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.
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effect modification of vaccine effectiveness by malaria transmission intensity
Délai: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Dose-specific vaccine effectiveness will be compared across prespecified malaria transmission levels within each country.
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effect modification of vaccine effectiveness by sex
Délai: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Dose-specific vaccine effectiveness will be estimated using vaccination-by-sex interaction terms and sex-stratified analyses.
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effect modification by other malaria prevention interventions
Délai: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Dose-specific vaccine effectiveness will be assessed in relation to seasonal malaria chemoprevention, insecticide-treated net use, and indoor residual spraying using interaction analyses.
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effectiveness according to vaccine dose timing
Délai: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
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.
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
Délai: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Adjusted vaccine effectiveness of 4 doses compared with 3 doses will be estimated using the odds of microscopy-confirmed malaria.
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Clinton Health Access Initiative Inc.

Collaborateurs

University of California, San Francisco
Institut de Recherche en Sciences de la Sante, Burkina Faso
Ministry of Health, Uganda
Ministry of Health, Burkina Faso
Infectious Diseases Research Collaboration, Uganda

Les enquêteurs

  • Chercheur principal: Isabel Rodriguez-Barraquer, MD, PhD, University of California, San Francisco
  • Chercheur principal: Halidou Tinto, PhD, Institut de Recherche en Sciences de la Santé (Burkina Faso)
  • Chercheur principal: Joaniter Nankabirwa, MD, PhD, Infectious Diseases Research Collaboration, Kampala, Uganda

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

14 juillet 2026

Achèvement primaire (Estimé)

1 juin 2027

Achèvement de l'étude (Estimé)

1 août 2027

Dates d'inscription aux études

Première soumission

3 août 2026

Première soumission répondant aux critères de contrôle qualité

3 août 2026

Première publication (Réel)

6 août 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

6 août 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

3 août 2026

Dernière vérification

1 août 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • AVERT-2026-01
  • INV-097482 (Autre subvention/numéro de financement: Gates Foundation)
  • 2026-06-05 (Autre subvention/numéro de financement: Givewell)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

INDÉCIS

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

S'abonner