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Vacina contra influenza de dose alta versus padrão em receptores pediátricos de SOT (PSOT)

26 de outubro de 2026 atualizado por: National Institute of Allergy and Infectious Diseases (NIAID)

Comparação de vacinas contra influenza de dose alta versus padrão em receptores pediátricos de transplante de órgãos sólidos

Influenza virus is a significant pathogen in pediatric solid organ transplant (SOT) recipients. However, these individuals respond poorly to standard-dose (SD) inactivated influenza vaccine (IIV). Recent studies have investigated two strategies to overcome poor immune responses in SOT recipients: (1) administration of high-dose (HD)-IIV compared to SD-IIV and (2) two doses of SD-IIV compared to one dose of SD-IIV in the same influenza season. One study compared HD-IIV vs. SD-IIV in adult SOT recipients and noted that HD-IIV was safe and more immunogenic; however, the median post-transplant period was 38 months. A phase I pediatric study comparing a single dose of HD-IIV vs. SD-IIV was safe with higher immunogenicity, but the study was limited by small sample size and median post-transplant vaccine administration was 26 months. In another phase II trial of adult SOT recipients, two doses of SD-IIV one month apart compared to one-dose of SD-IIV revealed modestly increased immunogenicity when given at a median of 18 months post-transplant. Therefore, these studies lack both evaluation in the early post-transplant period and substantive pediatric populations. Additionally, the administration of two-doses of HD-IIV in the same influenza season has not been evaluated in pediatric SOT recipients. Thus, the optimal immunization strategy for pediatric SOT recipients less than 24 months post-transplant is unknown. In addition, immunologic predictors and correlates of influenza vaccine immunogenicity in pediatric SOT recipients have not been well-defined.

The central hypothesis of our proposal is that pediatric SOT recipients 1-23 months post-transplant who receive two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have similar safety but higher Hemagglutination Inhibition (HAI) geometric mean titers (GMTs) to influenza antigens compared to pediatric SOT recipients receiving two doses of SD-QIV.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

Study design: This is a phase II, multi-center, double-blind, randomized controlled immunogenicity and safety trial comparing two doses of HD-QIV or two doses of SD-QIV in pediatric SOT recipients.

Hypotheses:

  1. Pediatric SOT recipients who are 1-23 months out from transplant and are administered two doses of HD-QIV will develop higher Hemagglutination Inhibition (HAI) geometric mean titer (GMT) to influenza antigens compared to pediatric SOT recipients receiving two doses of SD-QIV, with Geometric Mean Titer Ratio (GMR) HD-QIV/SD-QIV greater than 1.0.
  2. Administration of HD-QIV in pediatric SOT recipients will be well tolerated and the safety profile will be similar to SD-QIV with regards to solicited local and systemic post-administration reactions.
  3. Baseline immunophenotypic markers of exhaustion, immune senescence, and immune activation at the pre-vaccine timepoint will correlate with post-vaccine HAI titers.

Study population: The study plans to enroll a total of approximately 312 pediatric heart, liver, and/or kidney transplant recipients between 1 and 23 months post-transplantation.

Study enrollment: The enrollment period will be over three-years. Participants will be randomized into one of two groups. Group 1 will receive two doses of SD-QIV (0.5 mL; 15μg of each influenza antigen) whereas Group 2 will receive two doses HD-QIV (0.7 mL; 60μg of each influenza antigen).

Influenza surveillance: Active surveillance for influenza-like symptoms will begin when influenza season starts in each site's community, defined in previous trials as identification of at least two positive respiratory tests for influenza, with at least 10% of diagnostic tests positive during two consecutive weeks in the local clinical or research laboratory. Enrollment will continue during influenza season with nasal swabs obtained at all main visits to document the occurrence of influenza virus both prior to and after vaccination. During the influenza season, the study staff will attempt to do a weekly telephone and/or electronic communication with the participants to detect and document any influenza-like illness (ILI) and any specific coronavirus disease of 2019 (COVID-19) like symptoms.

If participants meet ILI criteria and/or any specific coronavirus disease of 2019 (COVID-19) like symptoms (see below), an additional nasal swab will be collected*.

ILI criteria are met by occurrence of one of the conditions below:

  • Fever: ≥38°C (100.4°F)

  • Two or more of any of the following: respiratory symptoms (rhinorrhea, sinus congestion, post-nasal drip, shortness of breath, cough, wheezing, sputum production, sore throat, sneezing, watery eyes, ear pain, hoarseness); or systemic symptoms (myalgias, chills, chest pain, or headache); or new loss of taste or new loss of smell; or gastrointestinal symptoms (diarrhea or vomiting).

    • Per investigators' discretion at each individual site, a swab is not needed if there is a known non-respiratory cause of symptoms.

Tipo de estudo

Intervencional

Inscrição (Estimado)

312

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Estados Unidos
    • California
      • Stanford, California, Estados Unidos, 94305
        • Recrutamento
        • Stanford University
        • Contato:
    • Georgia
      • Atlanta, Georgia, Estados Unidos, 30322
    • Illinois
      • Chicago, Illinois, Estados Unidos, 60614
        • Recrutamento
        • Ann Robert H. Lurie Children's Hospital of Chicago
        • Contato:
    • Indiana
      • Indianapolis, Indiana, Estados Unidos, 46202
        • Recrutamento
        • Indiana University School of Medicine/Riley Hospital for Children
        • Contato:
    • Missouri
      • Kansas City, Missouri, Estados Unidos, 64108
        • Recrutamento
        • Children's Mercy Hospital
        • Contato:
    • Ohio
      • Cincinnati, Ohio, Estados Unidos, 45229
        • Recrutamento
        • Cincinnati Children's Hospital Medical Center
        • Contato:
    • Pennsylvania
      • Philadelphia, Pennsylvania, Estados Unidos, 19104
        • Recrutamento
        • Children's Hospital of Philadelphia
        • Contato:
      • Pittsburgh, Pennsylvania, Estados Unidos, 15224
        • Recrutamento
        • UPMC Children's Hospital of Pittsburgh
        • Contato:
    • Tennessee
      • Nashville, Tennessee, Estados Unidos, 37232
        • Recrutamento
        • Monroe Carell Jr. Children's Hospital at Vanderbilt
        • Contato:
    • Texas
      • Houston, Texas, Estados Unidos, 77030
        • Recrutamento
        • Texas Children's Hospital
        • Contato:
          • Christopher Williams
          • Número de telefone: 832-824-1580
          • E-mail: cwillia4@bcm.edu
    • Washington

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

3 anos a 17 anos (Filho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  1. Male or female, 3-17 years of age at time of enrollment

  2. Pediatric kidney, heart, and/or liver transplant recipient ≥1 month and <24 months post-transplant at the time of study immunization

    • Note: Inclusion of recipients of multiple organs is permitted but is limited to recipients of any combination of organs including kidney, heart and/or liver
    • Note: Participants undergoing re-transplantation are permitted

  3. Anticipated to be available for duration of the study

  4. Available by telephone, email, or text message

Exclusion Criteria:

  1. Inability (i.e. not able to understand and provide consent) or unwillingness of a participant/parent/legal guardian to give written informed consent or comply with study protocol
  2. History of severe hypersensitivity to influenza vaccination or anaphylaxis to eggs/egg protein
  3. History of severe latex hypersensitivity
  4. History of Guillain-Barre syndrome
  5. History of lung or intestine transplant
  6. HIV positive patients (testing within 24 months of enrollment)
  7. Receipt of current season's influenza vaccine post-transplant prior to enrollment in the study
  8. Currently pregnant or lactating (females of childbearing age may be enrolled based on self-report, urine pregnancy test must be performed prior to each influenza vaccine)
  9. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Prevenção
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Quadruplicar

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Two Doses Standard Dose Quadrivalent Inactivated Influenza Vaccine

Two doses of SD-QIV (0.5 mL; 15µg of each influenza antigen) 28-42 days apart
Biológico: Standard Dose Quadrivalent Inactivated Influenza Vaccine

Fluzone ® Quadrivalent is a vaccine indicated for active immunization for the prevention of influenza disease caused by two influenza A subtype viruses and two type B viruses contained in the vaccine.

Outros nomes:
  • Fluzone
Experimental: Two Doses High Dose Quadrivalent Inactivated Influenza Vaccine

Two doses of HD-QIV (0.7 mL; 60µg of each influenza antigen) 28-42 days apart
Biológico: High Dose Quadrivalent Inactivated Influenza Vaccine

Fluzone High-Dose (Influenza Vaccine) for intramuscular injection is an inactivated influenza vaccine, prepared from influenza viruses propagated in embryonated chicken eggs. The virus-containing allantoic fluid is harvested and inactivated with formaldehyde. Influenza virus is concentrated and purified in a linear sucrose density gradient solution using a continuous flow centrifuge. The virus is then chemically disrupted using a non-ionic surfactant, octylphenol ethoxylate (Triton® X-100), producing a "split virus". The split virus is further purified and then suspended in sodium phosphatebuffered isotonic sodium chloride solution. The Fluzone High-Dose process uses an additional concentration factor after the ultrafiltration step in order to obtain a higher hemagglutinin (HA) antigen concentration.

Outros nomes:
  • Fluzone Alta Dose

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Immunogenicity: Hemagglutination Inhibition (HAI) titers
Prazo: 4 weeks following the 2nd study vaccine

Antibody titers will be measured by hemagglutination inhibition assay.
4 weeks following the 2nd study vaccine
Safety: solicited local and systemic post-administration reactions
Prazo: in the first 7 days following each study vaccine

Post-vaccination local adverse events (pain, tenderness, swelling/induration, erythema/redness, swelling/induration size, and erythema/redness size) and systemic adverse events (Fatigue/malaise, headache, nausea, body ache/myalgia (not at the injection site), general activity level, vomiting, and fever).
in the first 7 days following each study vaccine

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Immunogenicity: Hemagglutination Inhibition (HAI) titers
Prazo: 4 weeks following 1st and 2nd doses of each study vaccine

Antibody titers will be measured by hemagglutination inhibition assay.
4 weeks following 1st and 2nd doses of each study vaccine
The number of participants achieving seroprotection and seroconversion for influenza virus.
Prazo: 4 weeks following the 1st and 2nd study vaccination

Antibody titers will be measured by hemagglutination inhibition assay. Seroconversion is defined as ≥ 4-fold rise in hemagglutination inhibition assay titers. Seroprotection is defined as ≥1:40 hemagglutination inhibition assay titer.
4 weeks following the 1st and 2nd study vaccination
Durability of immunogenicity
Prazo: 180 days after vaccine 2

Measured as Hemagglutination Inhibition (HAI) titer at end of season
180 days after vaccine 2

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

National Institute of Allergy and Infectious Diseases (NIAID)

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

26 de setembro de 2024

Conclusão Primária (Estimado)

1 de julho de 2027

Conclusão do estudo (Estimado)

1 de setembro de 2027

Datas de inscrição no estudo

Enviado pela primeira vez

1 de março de 2023

Enviado pela primeira vez que atendeu aos critérios de CQ

11 de julho de 2023

Primeira postagem (Real)

17 de julho de 2023

Atualizações de registro de estudo

Última Atualização Postada (Real)

28 de outubro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

26 de outubro de 2026

Última verificação

1 de outubro de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • DAIT RTB-019

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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