<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01680601</url>
  </required_header>
  <id_info>
    <org_study_id>GN12KH253</org_study_id>
    <nct_id>NCT01680601</nct_id>
  </id_info>
  <brief_title>Remote Ischaemic Preconditioning in Children Undergoing Cardiac Surgery</brief_title>
  <official_title>Effect of Remote Ischaemic Preconditioning in Cardiac Dysfunction and End-organ Injury Following Cardiac Surgery With Cardiopulmonary Bypass in Children.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NHS Greater Glasgow and Clyde</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NHS Greater Glasgow and Clyde</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Surgical correction of congenital heart defects in children requires the utilization of&#xD;
      cardiopulmonary bypass, a technique that temporarily substitutes heart and lung functions&#xD;
      during surgery. During this process the patient´s circulation is controlled by a bypass&#xD;
      machine which provides several functions:&#xD;
&#xD;
        1. Controls the patient's blood flow by pumping of blood in the patient's body.&#xD;
&#xD;
        2. Controls the correct oxygen levels in the patient's blood.&#xD;
&#xD;
        3. Regulates the temperature and fluid level of the blood. This process triggers negative&#xD;
           responses in the heart and throughout the whole body, potentially resulting in injury to&#xD;
           the heart and other organs such as brain, kidneys and lungs.&#xD;
&#xD;
      Remote ischaemic preconditioning (RIPC) describes a procedure that could potentially reduce&#xD;
      the injury to heart muscle during cardiac surgery. The procedure consists of the inflation of&#xD;
      a blood pressure cuff on the child's leg for three 5 minute cycles. This process acts by&#xD;
      briefly reducing blood flow to the leg muscle, which will then activate the body´s own&#xD;
      protective mechanisms and thereby reduce heart injury.&#xD;
&#xD;
      Several animal studies have been used to help the understanding of the mechanisms behind this&#xD;
      process, and trials in human adults have showed optimistic results; however evidence&#xD;
      regarding the paediatric population is limited and necessary since children present different&#xD;
      basal profiles, risks and requirements.&#xD;
&#xD;
      The investigators propose a randomized clinical trial assessing the efficacy of RIPC to&#xD;
      provide protection against injury to the heart and other organs in children going through&#xD;
      cardiac surgery using CPB at the Royal Hospital for Sick Children. The research project will&#xD;
      have a translational approach, integrating basic molecular mechanisms to clinical outcome.&#xD;
      The investigators hope it will allow the understanding and utilisation of the patient´s own&#xD;
      protective mechanisms, reducing CPB-related injury and ultimately improving patient outcome.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measurement of the final cardiac injury after cardiopulmonary bypass assessed by markers of cardiac injury and echocardiography.</measure>
    <time_frame>Pre and post operatively (immediately before and after surgery, 24 and 48 hours after surgery)</time_frame>
    <description>Echocardiography assessment will take place before surgery, 24 and 48 hours after surgery. Blood markers of cardiac injury: B-type natriuretic peptide and Troponin will be measured before surgery, immediately after surgery, 24 and 48 hours after surgery in order to establish changes in the markers between the mentioned pre and post-operative time points.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Protein and mRNA expression in the cardiac tissue related to the preconditioning process.</measure>
    <time_frame>Expression assessed at the time of tissue extraction</time_frame>
    <description>Cardiac tissue will be obtained only from patients who require tissue excision as part of the surgical procedure. Protein and mRNA expression will be assessed after extraction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>End organ damage assessment by measurement of markers relevant to lung and kidney function and evaluate a possible benefit from preconditioning.</measure>
    <time_frame>Pre and post operatively (immediately before and after surgery, 24 and 48 hours after surgery)</time_frame>
    <description>Blood markers (creatinin, cystatin C, Neutrophil gelatinase associated lipocalin,cGMP and Phosphodiesterase 5)will be measured before surgery, immediately after surgery, 24 and 48 hours after surgery in order to establish changes in the markers between the mentioned pre and post-operative time points.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic immune response assessment by measurement of inflammatory mediators such as cytokines and nitric oxide metabolites.</measure>
    <time_frame>Pre and postoperatively (immediately before and after surgery, 24 and 48 hours after surgery)</time_frame>
    <description>Inflammatory blood markers (MDA, isoprostanes, NO metabolites, Cytokines, adhesion molecules, among others)will be measured before surgery, immediately after surgery, 24 and 48 hours after surgery in order to establish changes in the markers between the mentioned pre and post-operative time points</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">51</enrollment>
  <condition>Ischaemic Reperfusion Injury</condition>
  <arm_group>
    <arm_group_label>RIPC group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients assigned to this arm will go through a remote ischaemic preconditioning (RIPC)protocol</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients assigned to this arm will not receive the intervention, however the protocol will be applied to a wooden block in order to maintain blinding to relatives and investigators.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Remote ischaemic preconditioning (RIPC)</intervention_name>
    <description>RIPC will be performed by 3 cycles of 5 minute leg ischaemia induced by inflation of a blood pressure cuff to 40 mmHg above the patient's systolic pressure. This protocol will be performed at two phases: 24 hours before surgery and during anaesthesia immediately prior to surgery.</description>
    <arm_group_label>RIPC group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children undergoing cardiac surgery for correction of congenital heart defects&#xD;
             utilizing cardiopulmonary bypass and cold blood cardioplegia strategy of myocardial&#xD;
             protection.&#xD;
&#xD;
          -  Children whose parents understand the child's condition, the purpose of the study and&#xD;
             are willing to participate.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Children whose parents either are unwilling or do not have sufficient understanding of&#xD;
             the study.&#xD;
&#xD;
          -  Emergency operations, where there is insufficient time to establish the study&#xD;
             protocol.&#xD;
&#xD;
          -  Premature children presenting a corrected gestational age under 35 weeks.&#xD;
&#xD;
          -  Presence of extracardiac abnormalities, apart from cases of Down and DiGeorge&#xD;
             syndromes which will be included.&#xD;
&#xD;
          -  Patients with known viral blood infections (e.g. HIV, Hepatitis B) or severe&#xD;
             congenital infection.&#xD;
&#xD;
          -  Patients with severe preoperative brain injury.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Days</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Royal Hospital for Sick Children - Yorkhill</name>
      <address>
        <city>Glasgow</city>
        <zip>G3 8SJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>September 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <last_update_submitted>April 17, 2015</last_update_submitted>
  <last_update_submitted_qc>April 17, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 20, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Glasgow</investigator_affiliation>
    <investigator_full_name>Maribel Verdesoto</investigator_full_name>
    <investigator_title>PhD student</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Reperfusion Injury</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01680601
org study id: GN12KH253
nct id: NCT01680601
lead sponsor: 
has dmc: No
Surgical correction of congenital heart defects in children requires the utilization of
      cardiopulmonary bypass, a technique that temporarily substitutes heart and lung functions
      during surgery. During this process the patient´s circulation is controlled by a bypass
      machine which provides several functions:

        1. Controls the patient's blood flow by pumping of blood in the patient's body.

        2. Controls the correct oxygen levels in the patient's blood.

        3. Regulates the temperature and fluid level of the blood. This process triggers negative
           responses in the heart and throughout the whole body, potentially resulting in injury to
           the heart and other organs such as brain, kidneys and lungs.

      Remote ischaemic preconditioning (RIPC) describes a procedure that could potentially reduce
      the injury to heart muscle during cardiac surgery. The procedure consists of the inflation of
      a blood pressure cuff on the child's leg for three 5 minute cycles. This process acts by
      briefly reducing blood flow to the leg muscle, which will then activate the body´s own
      protective mechanisms and thereby reduce heart injury.

      Several animal studies have been used to help the understanding of the mechanisms behind this
      process, and trials in human adults have showed optimistic results; however evidence
      regarding the paediatric population is limited and necessary since children present different
      basal profiles, risks and requirements.

      The investigators propose a randomized clinical trial assessing the efficacy of RIPC to
      provide protection against injury to the heart and other organs in children going through
      cardiac surgery using CPB at the Royal Hospital for Sick Children. The research project will
      have a translational approach, integrating basic molecular mechanisms to clinical outcome.
      The investigators hope it will allow the understanding and utilisation of the patient´s own
      protective mechanisms, reducing CPB-related injury and ultimately improving patient outcome.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Investigator)
measure: Measurement of the final cardiac injury after cardiopulmonary bypass assessed by markers of cardiac injury and echocardiography.
time frame: Pre and post operatively (immediately before and after surgery, 24 and 48 hours after surgery)
description: Echocardiography assessment will take place before surgery, 24 and 48 hours after surgery. Blood markers of cardiac injury: B-type natriuretic peptide and Troponin will be measured before surgery, immediately after surgery, 24 and 48 hours after surgery in order to establish changes in the markers between the mentioned pre and post-operative time points.
measure: Protein and mRNA expression in the cardiac tissue related to the preconditioning process.
time frame: Expression assessed at the time of tissue extraction
description: Cardiac tissue will be obtained only from patients who require tissue excision as part of the surgical procedure. Protein and mRNA expression will be assessed after extraction.
measure: End organ damage assessment by measurement of markers relevant to lung and kidney function and evaluate a possible benefit from preconditioning.
time frame: Pre and post operatively (immediately before and after surgery, 24 and 48 hours after surgery)
description: Blood markers (creatinin, cystatin C, Neutrophil gelatinase associated lipocalin,cGMP and Phosphodiesterase 5)will be measured before surgery, immediately after surgery, 24 and 48 hours after surgery in order to establish changes in the markers between the mentioned pre and post-operative time points.
measure: Systemic immune response assessment by measurement of inflammatory mediators such as cytokines and nitric oxide metabolites.
time frame: Pre and postoperatively (immediately before and after surgery, 24 and 48 hours after surgery)
description: Inflammatory blood markers (MDA, isoprostanes, NO metabolites, Cytokines, adhesion molecules, among others)will be measured before surgery, immediately after surgery, 24 and 48 hours after surgery in order to establish changes in the markers between the mentioned pre and post-operative time points
arm group label: RIPC group
arm group type: Experimental
description: Patients assigned to this arm will go through a remote ischaemic preconditioning (RIPC)protocol
arm group label: Control
arm group type: Placebo Comparator
description: Patients assigned to this arm will not receive the intervention, however the protocol will be applied to a wooden block in order to maintain blinding to relatives and investigators.
intervention type: Procedure
intervention name: Remote ischaemic preconditioning (RIPC)
description: RIPC will be performed by 3 cycles of 5 minute leg ischaemia induced by inflation of a blood pressure cuff to 40 mmHg above the patient's systolic pressure. This protocol will be performed at two phases: 24 hours before surgery and during anaesthesia immediately prior to surgery.
arm group label: RIPC group
intervention type: Procedure
intervention name: Placebo
arm group label: Control
criteria: 
gender: All
minimum age: 2 Days
maximum age: 16 Years
healthy volunteers: No
facility: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: University of Glasgow
investigator full name: Maribel Verdesoto
investigator title: PhD student
mesh term: Reperfusion Injury
mesh term: Ischemia