CMV Antiviral Prevention Strategies in D+R-Liver Transplants ("CAPSIL")
29 de julho de 2021 atualizado por: National Institute of Allergy and Infectious Diseases (NIAID)
Prophylaxis Versus Preemptive Therapy for the Prevention of CMV in High-Risk R-D+ Liver Transplant Recipients
This is a trial of preemptive therapy vs. prophylaxis for prevention of Cytomegalovirus (CMV) disease in R-D+ liver transplant patients.
Subjects will be randomized within 10 days of transplant to receive in an open label design, either antiviral prophylaxis with valganciclovir, 900 mg orally once daily or preemptive therapy (weekly monitoring for CMV viremia by plasma PCR) for 100 days post-randomization with initiation of oral valganciclovir 900mg orally twice daily at onset of CMV viremia and continued until plasma PCR is negative on two consecutive weekly PCR tests).
A minimum of 176 subjects will be enrolled in the study.
The study duration is 7 years.
The primary objective of this study is to compare prophylaxis versus preemptive therapy using valganciclovir for the prevention of CMV disease in R-/D+ liver transplant recipients.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
This is a prospective, randomized, multicenter trial of preemptive therapy vs. prophylaxis for prevention of Cytomegalovirus (CMV) disease in seronegative recipient- seropositive donor (R-D+) liver transplant patients.Subjects will be randomized within 10 days of transplant to receive in an open label design, either antiviral prophylaxis with valganciclovir 900 mg orally once daily or preemptive therapy for 100 days post-randomization with initiation of oral valganciclovir 900mg orally twice daily at onset of CMV viremia (monitored weekly) and continued until plasma PCR is negative on two consecutive weekly PCR tests.
Study participants will be followed during the intervention period (100 days post randomization) and until 12 months post-transplant for CMV disease, toxicity, and clinical outcomes (opportunistic infections, rejection, graft loss and mortality).
Drug safety labs will be assessed and recorded for the entire treatment period in both the prophylaxis and preemptive group.
Re-transplantation and all-cause mortality will also be assessed at study closure and no longer than 5 years after enrollment.
Additionally, the impact of the two CMV prevention strategies on CMV-specific cellular and humoral immune responses will be evaluated at 100 days after randomization, and 6 and 12 months post-transplant.
A minimum of 176 subjects will be enrolled in the study.
Allowing for over-enrollment to replace dropouts, up to 205 subjects may be enrolled to achieve the target enrollment of 176.
Subjects will be randomized into one of the two groups in 1:1 ratio.
The study duration is 7 years.
The primary objective of this study is to compare prophylaxis versus preemptive therapy using valganciclovir for the prevention of CMV disease in R-/D+ liver transplant recipients.
The secondary objectives are:1) to assess the two preventive strategies for clinical outcomes (major bacterial, fungal and non-CMV viral infections, rejection, graft loss and mortality) at one year post transplantation; 2) to assess the two preventive strategies for hematologic toxicity (assessment of neutropenia and receipt of hematopoietic growth factor during study days 1-107).
Tipo de estudo
Intervencional
Inscrição (Real)
205
Estágio
- Fase 4
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
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California
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Los Angeles, California, Estados Unidos, 90095-8358
- Ronald Reagan University of California Los Angeles Medical Center
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322-1013
- Emory Clinic - Transplant Center
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55905-0001
- Mayo Clinic, Rochester - Infectious Diseases
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New York
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New York, New York, Estados Unidos, 10029-6504
- Mount Sinai School of Medicine - Medicine - Infectious Diseases
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Pennsylvania
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Pittsburgh, Pennsylvania, Estados Unidos, 15213-3403
- University of Pittsburgh - Medicine - Infectious Diseases
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Washington
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Seattle, Washington, Estados Unidos, 98195-7110
- University of Washington - Medicine
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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
18 anos a 99 anos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Be > / = 18 years of age.
- Have negative Cytomegalovirus (CMV) serology (confirmed within 6 months of transplant) and receive a liver from a donor with positive CMV serology (R-/D+).
- Have received their first orthotopic liver transplant (the transplanted liver may be deceased donor or live donor graft) within 10 days prior.
- Have absolute neutrophil count > 1000/µL at randomization.
- If female, and not postmenopausal or surgically sterile, must have negative pregnancy test (serum or urine) within 48 hours prior to randomization and must also agree to use medically approved method of contraception. Acceptable methods include: barrier method, intrauterine device (hormonal or non-hormonal), oral hormonal contraceptives, abstinence for 100 days after randomization and 3 months after valganciclovir cessation.
-- If male, and has not had a vasectomy, he must agree to practice barrier method of contraception for 100 days after randomization and 3 months after valganciclovir cessation.
- Subject or legally authorized representative has provided written informed consent.
Exclusion Criteria:
- Currently enrolled in any interventional trial of an investigational therapeutic agent unless co-enrollment has been approved by study Principal Investigators (PIs) and the DMID prior to enrollment.
- Have hypersensitivity to acyclovir, ganciclovir or valganciclovir.
- Be breast-feeding mother.
- Have known Human immunodeficiency virus (HIV) infection (based on testing performed during the transplant evaluation process).
- Be undergoing multi organ transplant or have undergone prior organ transplant.
- Have expected life expectancy of less than 72 hours.
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: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Preemptive Therapy
900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test.
All dosages adjusted for renal dysfunction.
n=88
|
Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 100 days post transplantation as prophylaxis.
Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.
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Comparador Ativo: Prophylaxis
900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation.
All dosages adjusted for renal dysfunction.
n=88
|
Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 100 days post transplantation as prophylaxis.
Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Incidence of Cytomegalovirus (CMV) Disease.
Prazo: 365 days post-transplant
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CMV disease as verified by an independent end point committee
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365 days post-transplant
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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All-cause Mortality
Prazo: Up to 365 days post-transplant
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Survival probability at 1 year
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Up to 365 days post-transplant
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Incidence of Allograft Rejection
Prazo: Up to 365 days post-transplant
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Number of subjects with allograft rejection
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Up to 365 days post-transplant
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Graft Loss
Prazo: Up to 365 days post-transplant
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Incidence of graft loss (re-transplantation)
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Up to 365 days post-transplant
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Late-onset CMV Disease
Prazo: Up to 365 days post-transplant
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Incidence of late-onset CMV disease (occurring after 100 days post-randomization) as adjudicated by end point committee
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Up to 365 days post-transplant
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Bacterial Infections
Prazo: Up to 365 days post-transplant
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Incidence of bacterial opportunistic infections
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Up to 365 days post-transplant
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Major Fungal Infections
Prazo: Up to 365 days post-transplant
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Opportunistic fungal infections
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Up to 365 days post-transplant
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Major Non-CMV Viral Infections
Prazo: Up to 365 days post-transplant
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Incidence of non-CMV viral infections
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Up to 365 days post-transplant
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Neutropenia
Prazo: Day 1 through Day 107
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Incidence of neutropenia less than 1000/µL while on valganciclovir treatment
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Day 1 through Day 107
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Neutropenia Less Than 500
Prazo: prior to day 107
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ANC less than 500 while on valganciclovir
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prior to day 107
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Hematopoietic Growth Factors
Prazo: Day 1 through Day 107
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Hematopoietic growth factor receipt for ANC less than 500 during valganciclovir treatment.
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Day 1 through Day 107
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Publicações e links úteis
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Publicações Gerais
- Singh N, Winston DJ, Razonable RR, Lyon GM, Silveira FP, Wagener MM, Limaye AP. Risk Factors for Cytomegalovirus Viremia following Liver Transplantation With a Seropositive Donor and Seronegative Recipient Receiving Antiviral Therapy. J Infect Dis. 2021 Mar 29;223(6):1073-1077. doi: 10.1093/infdis/jiaa470.
- Singh N, Winston DJ, Razonable RR, Lyon GM, Silveira FP, Wagener MM, Stevens-Ayers T, Edmison B, Boeckh M, Limaye AP. Effect of Preemptive Therapy vs Antiviral Prophylaxis on Cytomegalovirus Disease in Seronegative Liver Transplant Recipients With Seropositive Donors: A Randomized Clinical Trial. JAMA. 2020 Apr 14;323(14):1378-1387. doi: 10.1001/jama.2020.3138.
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)
29 de outubro de 2012
Conclusão Primária (Real)
22 de junho de 2018
Conclusão do estudo (Real)
22 de junho de 2018
Datas de inscrição no estudo
Enviado pela primeira vez
2 de março de 2012
Enviado pela primeira vez que atendeu aos critérios de CQ
8 de março de 2012
Primeira postagem (Estimativa)
13 de março de 2012
Atualizações de registro de estudo
Última Atualização Postada (Real)
26 de agosto de 2021
Última atualização enviada que atendeu aos critérios de controle de qualidade
29 de julho de 2021
Última verificação
22 de março de 2018
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 11-0073
Informações sobre medicamentos e dispositivos, documentos de estudo
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Sim
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produto fabricado e exportado dos EUA
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