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Clinical and Genomic Responses to Open Heart Surgery

25. august 2013 oppdatert av: 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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Faktiske)

300

Fase

  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Canada
    • Ontario
      • Toronto, Ontario, Canada
        • Brian W. McCrindle

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

1 dag til 17 år (Barn)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Trippel

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 1
Fremgangsmåte: Remote ischemic preconditioning (RIPC)
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.
Aktiv komparator: 2
Fremgangsmåte: SHAM
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.

Hva måler studien?

Primære resultatmål

Resultatmål
Tidsramme
Impact of RIPC on length of hospital stay.
Tidsramme: Assessed through post-operative hospitalization.
Assessed through post-operative hospitalization.

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Gene expression patterns associated with effects of RIPC.
Tidsramme: Assessed and recorded during the first 24 hours after surgery.
Assessed and recorded during the first 24 hours after surgery.
Patterns of baseline gene expression predictive of the clinical and physiologic impact of cardiopulmonary bypass in children (SHAM group only).
Tidsramme: Assessed and recorded during the first 24 hours after surgery.
Assessed and recorded during the first 24 hours after surgery.
Impact of RIPC on clinical and physiologic markers related to ischemia-reperfusion injury after cardiac surgery in children.
Tidsramme: Assessed and recorded serially during the first 48 hours after surgery.
Assessed and recorded serially during the first 48 hours after surgery.
Neurodevelopmental Outcomes (Age < 2 years old at surgery)
Tidsramme: Follow-up at 12-18 months post-surgery
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.
Follow-up at 12-18 months post-surgery
Neurodevelopmental Outcomes (Age 2-6 years old at surgery)
Tidsramme: Follow-up at 12-18 months post-surgery
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.
Follow-up at 12-18 months post-surgery

Samarbeidspartnere og etterforskere

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Sponsor

The Hospital for Sick Children

Etterforskere

  • Hovedetterforsker: Brian W. McCrindle, MD MPH, The Hospital for Sick Children
  • Hovedetterforsker: Andrew N. Redington, MB, The Hospital for Sick Children

Publikasjoner og nyttige lenker

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Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. mars 2008

Primær fullføring (Faktiske)

1. desember 2012

Studiet fullført (Faktiske)

1. desember 2012

Datoer for studieregistrering

Først innsendt

27. mars 2008

Først innsendt som oppfylte QC-kriteriene

27. mars 2008

Først lagt ut (Anslag)

1. april 2008

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

27. august 2013

Siste oppdatering sendt inn som oppfylte QC-kriteriene

25. august 2013

Sist bekreftet

1. august 2013

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 1000011898

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Kliniske studier på Ischemia-reperfusion (IR) Injury

Kliniske studier på Remote ischemic preconditioning (RIPC)

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