Clinical and Genomic Responses to Open Heart Surgery
25 de agosto de 2013 atualizado por: Brian McCrindle, The Hospital for Sick Children
Clinical and Genomic Responses to Open Heart Surgery: A Randomized Controlled Trial of the Effects of Remote Ischemic Preconditioning
This study will be the first large scale randomized study of remote ischemic preconditioning (RIPC) ever performed and will define the role of this novel therapy as a clinical tool.
This study will also be the first to define preoperative gene expression profiles associated with poor postoperative outcomes in a control (SHAM) population of children undergoing cardiac surgery.
Finally, the role of RIPC in modifying these gene expression profiles will be examined.
Therefore, mechanistic insight into the proven ability of RIPC to improve markers of tissue injury, and the expected improvement in clinically relevant endpoints, will be examined.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
Remote ischemic preconditioning (RIPC) is a powerful, innate mechanism of protection against ischemia-reperfusion (IR) injury. During the course of previous investigations, it was shown in animal models that transient limb ischemia (our stimulus for generating remote ischemic preconditioning) leads to induction of a portfolio of myocardial genomic responses concerned with stress-response and repair mechanisms, reduces myocardial infarction after prolonged coronary occlusion, protects against cardiopulmonary bypass-induced neural, pulmonary and myocardial damage, and when administered to the recipient, reduces IR injury in the transplanted heart.
In humans, it has been have shown that RIPC downregulates genes responsible for pro-inflammatory pathways concerned with TNFα-signaling, apoptosis and exocytosis in circulating leukocytes, reduces ischemia-induced endothelial dysfunction, and decreases markers of myocardial and lung injury in a pilot study of children undergoing open heart surgery. However, the latter study was not powered to demonstrate differences in anatomic and age-related subgroups, or clinically relevant 'hard' end-points such as ventilation time, intensive care, and length of hospital stay.
Thus, we are now proposing a large-scale clinical study examining genetic predictors of clinically relevant postoperative outcomes, and how they are modified by remote preconditioning.
Tipo de estudo
Intervencional
Inscrição (Real)
300
Estágio
- Fase 3
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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Ontario
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Toronto, Ontario, Canadá
- Brian W. McCrindle
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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
1 dia a 17 anos (Filho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Subject age birth (>36 weeks gestation) to 17 years.
- Underlying cardiac anatomy and planned primary repair with no anticipated residual shunting. Repair must necessitate use of cardiopulmonary bypass.
- Informed consent/assent of subject, parent(s) or legal guardian as appropriate.
Exclusion Criteria:
- Current or recent ischemic insult, defined as vascular occlusion or episode of cardiorespiratory collapse requiring medical intervention occurring within 7 days of enrollment.
- Evidence in any system for organ dysfunction that requires medical intervention.
- Current treatment with systemic anticoagulation therapy or the presence of a bleeding diathesis.
- Presence of important pulmonary or airway disease requiring medical intervention.
- Current or previous (within 10 days of screening) use of systemic corticosteroids.
- Recent (within 7 days of screening) or current documented systemic infection or sepsis.
- Anticipated unavailability of an uninstrumented limb with no anatomic or physiologic abnormality precluding administration of RIPC stimulus using a standard blood pressure cuff.
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
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Triplo
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: 1
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The RIPC stimulus will be delivered in the OR prep room after the induction of anesthesia (while the anesthesiologist and staff are inserting vascular cannulae and preparing the patient for surgery).
Whenever possible, the left lower limb will be selected for delivery of the stimulus.
An appropriate sized cuff will be selected and connected to a hand aneroid sphygmomanometer.
A second cuff and hand aneroid sphygmomanometer will be placed beside the one connected to the study subject.
The cuff on the limb will be inflated and deflated to provide a total of four cycles of limb ischemia and reperfusion.
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Comparador Ativo: 2
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For this group, the procedure will be identical for that described for the RIPC stimulus, with the exception that the blood pressure cuff placed on the subject will not be inflated, but the second cuff, that has been placed beside, will be inflated.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
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Impact of RIPC on length of hospital stay.
Prazo: Assessed through post-operative hospitalization.
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Assessed through post-operative hospitalization.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Gene expression patterns associated with effects of RIPC.
Prazo: Assessed and recorded during the first 24 hours after surgery.
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Assessed and recorded during the first 24 hours after surgery.
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Patterns of baseline gene expression predictive of the clinical and physiologic impact of cardiopulmonary bypass in children (SHAM group only).
Prazo: Assessed and recorded during the first 24 hours after surgery.
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Assessed and recorded during the first 24 hours after surgery.
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Impact of RIPC on clinical and physiologic markers related to ischemia-reperfusion injury after cardiac surgery in children.
Prazo: Assessed and recorded serially during the first 48 hours after surgery.
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Assessed and recorded serially during the first 48 hours after surgery.
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Neurodevelopmental Outcomes (Age < 2 years old at surgery)
Prazo: Follow-up at 12-18 months post-surgery
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Patients less than a two years of age at the time of surgery will return at 12 -18 months postoperative to be assessed using the BSID- III.
During the same visit, parents will complete questionnaires pertaining to their child's behavior and adaptive behavior; the parent version of the Child Behavior Checklist and the parent version of the Vineland Adaptive Behavior Scales - II.
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Follow-up at 12-18 months post-surgery
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Neurodevelopmental Outcomes (Age 2-6 years old at surgery)
Prazo: Follow-up at 12-18 months post-surgery
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Patients greater than two years of age at the time of surgery will be assessed using the Wechsler Preschool and Primary Scale of Intelligence-Revised, the Peabody Picture Vocabulary Test - IV and the Beery-Buktenica Developmental Test of Visual-Motor Integration, 5th Edition.
Parents will complete questionnaires pertaining to their child's behavior and adaptive behavior; the parent version of the Child Behavior Checklist and the parent version of the Vineland Adaptive Behavior Scales - II.
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Follow-up at 12-18 months post-surgery
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Investigador principal: Brian W. McCrindle, MD MPH, The Hospital for Sick Children
- Investigador principal: Andrew N. Redington, MB, The Hospital for Sick Children
Publicações e links úteis
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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
1 de março de 2008
Conclusão Primária (Real)
1 de dezembro de 2012
Conclusão do estudo (Real)
1 de dezembro de 2012
Datas de inscrição no estudo
Enviado pela primeira vez
27 de março de 2008
Enviado pela primeira vez que atendeu aos critérios de CQ
27 de março de 2008
Primeira postagem (Estimativa)
1 de abril de 2008
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
27 de agosto de 2013
Última atualização enviada que atendeu aos critérios de controle de qualidade
25 de agosto de 2013
Última verificação
1 de agosto de 2013
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 1000011898
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