xml: <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/NCT05996120</url>
    </required_header>
    <id_info>
      <org_study_id>0910</org_study_id>
      <secondary_id>IRAS</secondary_id>
      <nct_id>NCT05996120</nct_id>
    </id_info>
    <brief_title>Study on Optimal Temperature During Cardiopulmonary Bypass (THERMIC-4)</brief_title>
    <acronym>THERMIC-4</acronym>
    <official_title>Normothermic Versus Hypothermic Cardiopulmonary Bypass in Adult Cardiac Surgery: a Multicentre Feasibility Randomised Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Leicester</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>NHS National Waiting Times Centre Board</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Sheffield Teaching Hospitals NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Oxford University Hospitals NHS Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Guy's and St Thomas' NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Hull University Teaching Hospitals NHS Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>University Hospitals Bristol and Weston NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Blackpool Teaching Hospitals NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>University Hospitals, Leicester</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Leicester</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        In order to perform heart surgery, a machine called cardiopulmonary bypass (CPB), or more&#xD;
        commonly known as a heart-lung machine, is used to maintain the circulation of oxygenated&#xD;
        blood needed by the rest of the body and its organs.&#xD;
  &#xD;
        Historically, when a patient is connected to CPB, their body is cooled below the normal body&#xD;
        temperature. This is known as hypothermia. This is because scientific studies have previously&#xD;
        shown that reduced body temperature lowers metabolism and therefore offers more protection to&#xD;
        the brain and other organs due to the reduced oxygen requirement. The evidence supporting&#xD;
        this practice, however, has been challenged throughout the history of cardiac surgery, with&#xD;
        studies supporting that normothermia, or normal body temperature, is a safe alternative.&#xD;
        Despite this, the practice of hypothermia has persisted. Published data from a survey of 139&#xD;
        cardiac surgeons in the United Kingdom showed that 84% still routinely employ hypothermic CPB&#xD;
        during surgery.&#xD;
  &#xD;
        To assess whether normothermic or hypothermic CPB is safer, a clinical trial requiring a&#xD;
        large sample size and high recruitment rates will be required. Therefore, the investigators&#xD;
        aim to assess firstly the feasibility of trial recruitment and allocation adherence in this&#xD;
        study. 100 adults across 10 different cardiac surgery centres in the United Kingdom will be&#xD;
        recruited to a multicentre feasibility randomised controlled trial comparing normothermia&#xD;
        (active comparator) against hypothermia (control comparator) during cardiopulmonary bypass in&#xD;
        cardiac surgery. This study will also test the ability of the Cardiothoracic&#xD;
        Interdisciplinary Research Network (CIRN), a trainee-led research collaborative, to collect&#xD;
        pilot data on Major Adverse Cardiac and Cerebrovascular Events (MACCE) using a&#xD;
        regulation-approved electronic application HealthBitⓇ. Participants will also be asked to&#xD;
        complete quality of life surveys. The results of this study will subsequently inform a large,&#xD;
        adequately powered randomised controlled trial for optimal temperature management during CPB.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Primary Objective&#xD;
  &#xD;
        To assess the feasibility of trial recruitment and delivery to target in the United Kingdom&#xD;
        of a multicentre randomised controlled trial on normothermia versus hypothermia during&#xD;
        cardiopulmonary bypass in adult cardiac surgery.&#xD;
  &#xD;
        Secondary Objective&#xD;
  &#xD;
        To assess the feasibility of conducting a multicentre randomized controlled trial (RCT) using&#xD;
        a novel Good Clinical Practice (GCP) approved remote data capture as the primary trial&#xD;
        database alongside analysis of routinely collected healthcare data.&#xD;
  &#xD;
        To obtain pilot data, undertaken by the Cardiothoracic Interdisciplinary Research Network&#xD;
        (CIRN), to inform a subsequent large, adequately powered RCT for optimal temperature&#xD;
        management during CPB.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">June 2024</completion_date>
    <primary_completion_date type="Anticipated">February 2024</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>
      <intervention_model_description>Parallel group, open label, statistician blinded, multicentre, randomised controlled feasibility trial.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Total number of participants recruited over a 6 month period</measure>
      <time_frame>6 months</time_frame>
      <description>The target recruitment rate is 1 participant per week per centre. The feasibility trial will be considered positive if 80% of target met, together with outcome 2.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Adherence rate to allocation</measure>
      <time_frame>6 months</time_frame>
      <description>The feasibility trial will be considered positive if 74%* of target adherence to trial allocation is met, together with outcome 1.&#xD;
  *74% is derived from 80% of target adherence of 92% as per Warm Heart Study</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Incidence of 6-week composite endpoint of Major Adverse Cardiac and Cerebrovascular Events (MACCE)</measure>
      <time_frame>6 weeks</time_frame>
      <description>MACCE is defined as any post-operative death, stroke, new intra-aortic balloon pump insertion, new renal replacement therapy, re-operation and major bleeding in this feasibility trial.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of deep sternal wound infection, with or without treatment</measure>
      <time_frame>6 weeks</time_frame>
      <description>Deep sternal wound infection is defined with at least one of the following criteria:&#xD;
  (I) an organism is isolated from culture of mediastinal tissue or fluid (II) evidence of mediastinitis seen intraoperatively (III) presence of chest pain, sternal instability, or fever (&gt; 38 °C), and purulent drainage from the mediastinum or isolation of organism present in a blood culture or from the mediastinal area.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of all adverse events</measure>
      <time_frame>6 weeks</time_frame>
      <description>Composite of all reported adverse events. Examples of adverse events include: low cardiac output, suspected myocardial infarction, arrhythmias, infections, haemorrhage, and pulmonary embolus.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Critical care length of stay</measure>
      <time_frame>6 weeks</time_frame>
      <description>Number of days a participant is admitted in cardiac critical care unit</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Post-operative length of stay</measure>
      <time_frame>6 weeks</time_frame>
      <description>Number of days a participant is an in-patient after index operation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Frequency of post-discharge healthcare resource utilisation</measure>
      <time_frame>6 weeks</time_frame>
      <description>Number of visits to general practitioner (GP) and/or hospital, either district general hospital or tertiary hospital, will be recorded via HealthBitⓇ.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of life post-operation: Medical Outcomes Study Short-Form 36 (SF-36)</measure>
      <time_frame>6 weeks</time_frame>
      <description>Quality of life questionnaire (SF-36) will administered before surgery and at 6-week follow up</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of life post-operation: European Quality of Life-5 Dimensions (EQ-5D)</measure>
      <time_frame>6 weeks</time_frame>
      <description>Quality of life questionnaire (EQ-5D) will administered before surgery and at 6-week follow up</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of life post-operation: World Health Organisation Disability Assessment Schedule (WHODAS)</measure>
      <time_frame>6 weeks</time_frame>
      <description>Quality of life questionnaire (WHODAS) will administered before surgery and at 6-week follow up</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical Frailty Scale (CFS) post-operation</measure>
      <time_frame>6 weeks</time_frame>
      <description>Clinical Frailty Scale will be recorded before surgery and at 6-week follow up</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Data completeness</measure>
      <time_frame>6 months</time_frame>
      <description>Data recorded on HealthBitⓇ will be assessed for percentage of completion</description>
    </other_outcome>
    <other_outcome>
      <measure>Attrition rate</measure>
      <time_frame>6 months</time_frame>
      <description>For ascertainment of the primary outcome and for planning of future large-scale study</description>
    </other_outcome>
    <other_outcome>
      <measure>User satisfaction of ResearchApp</measure>
      <time_frame>6 months</time_frame>
      <description>Participants will be invited to complete optional survey on user satisfaction of ResearchApp</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Ischemic Heart Disease</condition>
    <condition>Valvular Heart Disease</condition>
    <condition>Cardiovascular Diseases</condition>
    <condition>Surgery-Complications</condition>
    <arm_group>
      <arm_group_label>Hypothermic Cardiopulmonary Bypass</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients allocated to this arm will undergo standard care for coronary artery bypass grafting and/or valve surgery with mild hypothermia during CPB.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Normothermic Cardiopulmonary Bypass</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients allocated to this arm will undergo intervention care for coronary artery bypass grafting and/or valve surgery with normothermia hypothermia during CPB.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Hypothermic Cardiopulmonary Bypass</intervention_name>
      <description>Mild hypothermia (between 32 - 35 °C) during cardiopulmonary bypass</description>
      <arm_group_label>Hypothermic Cardiopulmonary Bypass</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Normothermic Cardiopulmonary Bypass</intervention_name>
      <description>Normothermia (active maintenance of temperature between 36.5 °C to 37.5°C; no active cooling below 36.5 °C) during cardiopulmonary bypass</description>
      <arm_group_label>Normothermic Cardiopulmonary Bypass</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          INCLUSION CRITERIA&#xD;
  &#xD;
          Participants may enter the trial if all of the following apply&#xD;
  &#xD;
            1. Adult patients (≥ 18 years) scheduled for coronary artery bypass surgery and/or valve&#xD;
               replacement/ repair, either in the elective or urgent setting.&#xD;
  &#xD;
            2. European System for Cardiac Operative Risk Evaluation (EuroSCORE) II of 2 or higher.&#xD;
  &#xD;
            3. Able to understand and communicate to provide informed consent.&#xD;
  &#xD;
            4. Able to read and understand the English language.&#xD;
  &#xD;
          EXCLUSION CRITERIA&#xD;
  &#xD;
          Participants may not enter the trial if any of the following apply:&#xD;
  &#xD;
            1. Patients undergoing coronary artery bypass surgery in combination with other&#xD;
               procedures including cardiac or vascular procedures that require deep hypothermic&#xD;
               arrest.&#xD;
  &#xD;
            2. Patients undergoing emergency or salvage surgery.&#xD;
  &#xD;
            3. Patients undergoing off-pump cardiac surgery.&#xD;
  &#xD;
            4. Patients who are participating in another interventional trial.&#xD;
  &#xD;
            5. Unable to provide informed consent.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Gavin J Murphy, FRCS, MD, MBChB, BSc</last_name>
      <phone>0116 258 3054</phone>
      <email>gjm19@le.ac.uk</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Ann Cheng, MBChB, MSc</last_name>
      <email>ann.cheng1@nhs.net</email>
    </overall_contact_backup>
    <verification_date>June 2023</verification_date>
    <study_first_submitted>July 2, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 10, 2023</last_update_submitted>
    <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 16, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>cardiopulmonary bypass</keyword>
    <keyword>hypothermia</keyword>
    <keyword>myocardial protection</keyword>
    <keyword>neurologic protection</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cardiovascular Diseases</mesh_term>
      <mesh_term>Heart Diseases</mesh_term>
      <mesh_term>Myocardial Ischemia</mesh_term>
      <mesh_term>Coronary Artery Disease</mesh_term>
      <mesh_term>Heart Valve Diseases</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Fully anonymised individual participant data can be made available on request for future studies with ethics approval.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_time_frame>The investigators will retain the fully anonymised dataset indefinitely. The duration for which this will be shared will be determined on a case-by-case basis and defined in a Data Sharing Agreement.</ipd_time_frame>
      <ipd_access_criteria>Requests must be from studies with appropriate ethics approval in place.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05996120
  org study id: 0910
  secondary id: IRAS
  nct id: NCT05996120
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  In order to perform heart surgery, a machine called cardiopulmonary bypass (CPB), or more
        commonly known as a heart-lung machine, is used to maintain the circulation of oxygenated
        blood needed by the rest of the body and its organs.
  
        Historically, when a patient is connected to CPB, their body is cooled below the normal body
        temperature. This is known as hypothermia. This is because scientific studies have previously
        shown that reduced body temperature lowers metabolism and therefore offers more protection to
        the brain and other organs due to the reduced oxygen requirement. The evidence supporting
        this practice, however, has been challenged throughout the history of cardiac surgery, with
        studies supporting that normothermia, or normal body temperature, is a safe alternative.
        Despite this, the practice of hypothermia has persisted. Published data from a survey of 139
        cardiac surgeons in the United Kingdom showed that 84% still routinely employ hypothermic CPB
        during surgery.
  
        To assess whether normothermic or hypothermic CPB is safer, a clinical trial requiring a
        large sample size and high recruitment rates will be required. Therefore, the investigators
        aim to assess firstly the feasibility of trial recruitment and allocation adherence in this
        study. 100 adults across 10 different cardiac surgery centres in the United Kingdom will be
        recruited to a multicentre feasibility randomised controlled trial comparing normothermia
        (active comparator) against hypothermia (control comparator) during cardiopulmonary bypass in
        cardiac surgery. This study will also test the ability of the Cardiothoracic
        Interdisciplinary Research Network (CIRN), a trainee-led research collaborative, to collect
        pilot data on Major Adverse Cardiac and Cerebrovascular Events (MACCE) using a
        regulation-approved electronic application HealthBitⓇ. Participants will also be asked to
        complete quality of life surveys. The results of this study will subsequently inform a large,
        adequately powered randomised controlled trial for optimal temperature management during CPB.
  Primary Objective
  
        To assess the feasibility of trial recruitment and delivery to target in the United Kingdom
        of a multicentre randomised controlled trial on normothermia versus hypothermia during
        cardiopulmonary bypass in adult cardiac surgery.
  
        Secondary Objective
  
        To assess the feasibility of conducting a multicentre randomized controlled trial (RCT) using
        a novel Good Clinical Practice (GCP) approved remote data capture as the primary trial
        database alongside analysis of routinely collected healthcare data.
  
        To obtain pilot data, undertaken by the Cardiothoracic Interdisciplinary Research Network
        (CIRN), to inform a subsequent large, adequately powered RCT for optimal temperature
        management during CPB.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Parallel group, open label, statistician blinded, multicentre, randomised controlled feasibility trial.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Total number of participants recruited over a 6 month period
  time frame: 6 months
  description: The target recruitment rate is 1 participant per week per centre. The feasibility trial will be considered positive if 80% of target met, together with outcome 2.
  measure: Adherence rate to allocation
  time frame: 6 months
  description: The feasibility trial will be considered positive if 74%* of target adherence to trial allocation is met, together with outcome 1.
  *74% is derived from 80% of target adherence of 92% as per Warm Heart Study
  measure: Incidence of 6-week composite endpoint of Major Adverse Cardiac and Cerebrovascular Events (MACCE)
  time frame: 6 weeks
  description: MACCE is defined as any post-operative death, stroke, new intra-aortic balloon pump insertion, new renal replacement therapy, re-operation and major bleeding in this feasibility trial.
  measure: Incidence of deep sternal wound infection, with or without treatment
  time frame: 6 weeks
  description: Deep sternal wound infection is defined with at least one of the following criteria:
  (I) an organism is isolated from culture of mediastinal tissue or fluid (II) evidence of mediastinitis seen intraoperatively (III) presence of chest pain, sternal instability, or fever (> 38 °C), and purulent drainage from the mediastinum or isolation of organism present in a blood culture or from the mediastinal area.
  measure: Incidence of all adverse events
  time frame: 6 weeks
  description: Composite of all reported adverse events. Examples of adverse events include: low cardiac output, suspected myocardial infarction, arrhythmias, infections, haemorrhage, and pulmonary embolus.
  measure: Critical care length of stay
  time frame: 6 weeks
  description: Number of days a participant is admitted in cardiac critical care unit
  measure: Post-operative length of stay
  time frame: 6 weeks
  description: Number of days a participant is an in-patient after index operation
  measure: Frequency of post-discharge healthcare resource utilisation
  time frame: 6 weeks
  description: Number of visits to general practitioner (GP) and/or hospital, either district general hospital or tertiary hospital, will be recorded via HealthBitⓇ.
  measure: Quality of life post-operation: Medical Outcomes Study Short-Form 36 (SF-36)
  time frame: 6 weeks
  description: Quality of life questionnaire (SF-36) will administered before surgery and at 6-week follow up
  measure: Quality of life post-operation: European Quality of Life-5 Dimensions (EQ-5D)
  time frame: 6 weeks
  description: Quality of life questionnaire (EQ-5D) will administered before surgery and at 6-week follow up
  measure: Quality of life post-operation: World Health Organisation Disability Assessment Schedule (WHODAS)
  time frame: 6 weeks
  description: Quality of life questionnaire (WHODAS) will administered before surgery and at 6-week follow up
  measure: Clinical Frailty Scale (CFS) post-operation
  time frame: 6 weeks
  description: Clinical Frailty Scale will be recorded before surgery and at 6-week follow up
  measure: Data completeness
  time frame: 6 months
  description: Data recorded on HealthBitⓇ will be assessed for percentage of completion
  measure: Attrition rate
  time frame: 6 months
  description: For ascertainment of the primary outcome and for planning of future large-scale study
  measure: User satisfaction of ResearchApp
  time frame: 6 months
  description: Participants will be invited to complete optional survey on user satisfaction of ResearchApp
  arm group label: Hypothermic Cardiopulmonary Bypass
  arm group type: Active Comparator
  description: Patients allocated to this arm will undergo standard care for coronary artery bypass grafting and/or valve surgery with mild hypothermia during CPB.
  arm group label: Normothermic Cardiopulmonary Bypass
  arm group type: Active Comparator
  description: Patients allocated to this arm will undergo intervention care for coronary artery bypass grafting and/or valve surgery with normothermia hypothermia during CPB.
  intervention type: Procedure
  intervention name: Hypothermic Cardiopulmonary Bypass
  description: Mild hypothermia (between 32 - 35 °C) during cardiopulmonary bypass
  arm group label: Hypothermic Cardiopulmonary Bypass
  intervention type: Procedure
  intervention name: Normothermic Cardiopulmonary Bypass
  description: Normothermia (active maintenance of temperature between 36.5 °C to 37.5°C; no active cooling below 36.5 °C) during cardiopulmonary bypass
  arm group label: Normothermic Cardiopulmonary Bypass
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Gavin J Murphy, FRCS, MD, MBChB, BSc
  phone: 0116 258 3054
  email: gjm19@le.ac.uk
  last name: Ann Cheng, MBChB, MSc
  email: ann.cheng1@nhs.net
  responsible party type: Sponsor
  mesh term: Cardiovascular Diseases
  mesh term: Heart Diseases
  mesh term: Myocardial Ischemia
  mesh term: Coronary Artery Disease
  mesh term: Heart Valve Diseases
  sharing ipd: Yes
  ipd description: Fully anonymised individual participant data can be made available on request for future studies with ethics approval.
  ipd info type: Study Protocol
  ipd info type: Clinical Study Report (CSR)
  ipd time frame: The investigators will retain the fully anonymised dataset indefinitely. The duration for which this will be shared will be determined on a case-by-case basis and defined in a Data Sharing Agreement.
  ipd access criteria: Requests must be from studies with appropriate ethics approval in place.