<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/NCT03288558</url>
  </required_header>
  <id_info>
    <org_study_id>17-5171</org_study_id>
    <nct_id>NCT03288558</nct_id>
  </id_info>
  <brief_title>Protective Mechanical VENTilation Strategy in Patients Undergoing CARDiac Surgery</brief_title>
  <official_title>Protective Mechanical VENTilation Strategy in Patients Undergoing CARDiac Surgery (VENT CARD Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Health Network, Toronto</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Heart surgery is a life-saving intervention for hundreds of thousands of patients each year&#xD;
      worldwide. Advances in technology and medical expertise have improved outcomes for these&#xD;
      patients over the years. However, despite such advances, approximately 30% of patients&#xD;
      develop lung complications (also called &quot;pulmonary complications&quot;) after heart surgery, which&#xD;
      result in prolonged hospital stay, increased mortality and healthcare costs.&#xD;
&#xD;
      During and immediately after heart surgery, the patient's breathing needs to be artificially&#xD;
      controlled by a breathing machine, called &quot;mechanical ventilator&quot;. The medical literature has&#xD;
      reported that in critically ill patients the use of specific settings on the breathing&#xD;
      machine (so called &quot;protective mechanical ventilation&quot;) prevents lung complications and&#xD;
      significantly decreases mortality. Studies show that such settings could also be beneficial&#xD;
      for patients that undergo several types of planned surgery, however data regarding heart&#xD;
      surgery patients (the most vulnerable to lung complications) are lacking.The aim of our study&#xD;
      is to test whether the use of protective mechanical ventilation settings during and after&#xD;
      heart surgery reduces lung complications compared to the current standard of care. The main&#xD;
      innovation of this study is the application of a novel protective mechanical ventilation&#xD;
      strategy to patients undergoing cardiac surgery, in order to reduce post-operative pulmonary&#xD;
      complications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Postoperative pulmonary complications are frequent after cardiac surgery, affecting&#xD;
      approximately 30% of all patients. Such complications result in increased morbidity,&#xD;
      mortality and health care utilization. During and immediately after surgery, mechanical&#xD;
      ventilation is required to control the patient's breathing. Recent scientific literature&#xD;
      showed the striking importance of specific mechanical ventilation settings (which often&#xD;
      constituted a bundle of interventions and were generally called &quot;protective mechanical&#xD;
      ventilation&quot;) in other areas of medicine (i.e., critical care, abdominal surgery, management&#xD;
      of organ donors) to prevent the onset or propagation of lung injury as well as multiple organ&#xD;
      dysfunction. These protective settings include tidal volume of 6 ml/kg of ideal body weight&#xD;
      (as opposed to the traditional tidal volume of 10-12 ml/kg), use of positive end expiratory&#xD;
      pressure (PEEP), recruitment maneuvers (temporary periodic application of higher respiratory&#xD;
      pressures or volumes on the mechanical ventilator in order to re-open collapsed areas of the&#xD;
      lungs) and attention at avoiding lung collapse during patient transfer and suctioning (i.e.&#xD;
      maintaining PEEP during transfer and avoiding disconnection from the breathing circuit during&#xD;
      suctioning of respiratory secretions). Such interventions could play an even more important&#xD;
      role during cardiac surgery, where several insults to the lung take place. These insults&#xD;
      result from the inflammatory cascade triggered by cardiopulmonary bypass (CPB), myocardial&#xD;
      injury and areas of lung collapse (atelectasis). Indeed, a recent retrospective study showed&#xD;
      that the tidal volume utilized during and after cardiac surgery impacts significantly on&#xD;
      organ dysfunction, with a tidal volume less than 10 ml/kg of ideal body weight providing&#xD;
      better outcomes than larger tidal volumes.&#xD;
&#xD;
      The investigators hypothesize that our proposed bundle of protective mechanical ventilation&#xD;
      settings aimed at minimizing lung injury by continuation of mechanical ventilation during&#xD;
      cardiopulmonary bypass, recruitment maneuvers, and use of systems that prevent lung collapse&#xD;
      during patient transfer and suctioning (i.e. PEEP valves and closed respiratory circuits)&#xD;
      will reduce postoperative pulmonary complications compared to the current standard of care,&#xD;
      hence significantly improving patients outcomes and reducing health care costs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 7, 2017</start_date>
  <completion_date type="Anticipated">April 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2021</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>Prevention</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Post-operative pulmonary complications</measure>
    <time_frame>for 7 days post operatively</time_frame>
    <description>Daily chart review and assessment of any pulmonary complications documented</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ventilator free days</measure>
    <time_frame>Post op day 1-28 days</time_frame>
    <description>number of days without a ventilator&#xD;
Number of days without ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensive care length of stay</measure>
    <time_frame>Post op day 1-28 days</time_frame>
    <description>Number of days in the intensive care unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>Post op day 1-28 days</time_frame>
    <description>Number of days in the hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of mechanical ventilation</measure>
    <time_frame>Post op day 1-28 days</time_frame>
    <description>Length of time on a ventilator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ease of surgical access</measure>
    <time_frame>Intraoperatively during surgery</time_frame>
    <description>Ability of the surgeon to access the surgical field during cardiopulmonary bypass using a 5 point Likert scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Barotrauma</measure>
    <time_frame>in the first 7 days after surgery</time_frame>
    <description>defined as radiological evidence of pneumothorax and/or pneumomediastinum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical complications</measure>
    <time_frame>From the day of surgery to 48 hours post surgery</time_frame>
    <description>death, myocardial infarction, stroke, acute liver injury, and chest reopening</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Kidney Injury</measure>
    <time_frame>Day of surgery to 28 days</time_frame>
    <description>Incidence of Acute Kidney Injury across the study population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>Day of surgery to 90-day</time_frame>
    <description>Incidence of mortality across the study population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Home and alive</measure>
    <time_frame>up to 30 days after surgery</time_frame>
    <description>to evaluate days at home</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">310</enrollment>
  <condition>Pulmonary Complications</condition>
  <condition>Cardiac Surgery</condition>
  <arm_group>
    <arm_group_label>Intervention Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects randomized to the intervention group will receive a comprehensive perioperative mechanical ventilation strategy that includes a bundle of protective settings (use of PEEP, recruitment maneuvers and continuation of mechanical ventilation during CPB).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Subjects randomized to the control group will receive mechanical ventilation according to the current usual care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>A comprehensive perioperative mechanical ventilation strategy</intervention_name>
    <description>1) Intervention group.&#xD;
Recruitment maneuvers (doubling the tidal volumes for 10 consecutive breaths) every 30min and after every time mechanical ventilation is stopped for surgical reasons, suctioning occurs or the breathing circuit is disconnected&#xD;
Mechanical ventilation will be continued during CPB (PEEP 5 cm H2O, respiratory rate 8/min, Tidal Volume 6 ml/kg PBW, FiO2 21%&#xD;
Avoidance of lung de-recruitment during patient's transfer (use of PEEP via PEEP valves, endotracheal tube clamps during disconnection from the breathing circuit)&#xD;
Avoidance of disconnection from respiratory circuit during respiratory secretions suctioning (applying closed suction circuits)&#xD;
For the remaining aspects the mechanical ventilation settings will be the same as in the control group.&#xD;
Tidal volume 6ml/kg PBW PEEP 5cm H20 FiO2 to target SatO2 of 92-97% Discontinuation of mechanical ventilation during cardiopulmonary bypass</description>
    <arm_group_label>Intervention Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18 years old&#xD;
&#xD;
          -  Scheduled for elective Coronary Artery Bypass Graft, Single valve repair or&#xD;
             replacement, or Coronary Artery Bypass Graft plus Single Valve repair or replacement,&#xD;
             with the use of Cardiopulmonary Bypass (CPB), aortic clamp and cardioplegia,&#xD;
             sternotomy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Clinically significant Congenital Heart Disease&#xD;
&#xD;
          -  Surgery with planned thoracotomy approach with one lung ventilation&#xD;
&#xD;
          -  Body mass index (the weight in kilograms divided by the square of the height in&#xD;
             meters) of 40 or higher,&#xD;
&#xD;
          -  Receipt of positive pressure mechanical ventilation (invasive and non-invasive) within&#xD;
             the 2 weeks preceding surgery (excluding routine treatment for obstructive sleep apnea&#xD;
             syndrome)&#xD;
&#xD;
          -  Severe chronic respiratory disease, as indicated by any of:&#xD;
&#xD;
          -  Baseline FEV1 &lt; 20 ml/kg predicted body weight&#xD;
&#xD;
          -  Pre-existing chronic interstitial lung disease with chronic interstitial infiltration&#xD;
             on chest X-ray&#xD;
&#xD;
          -  Documented chronic CO2 retention (PaCO2 &gt; 50 mm Hg) and/or chronic hypoxaemia (PaO2&lt;55&#xD;
             mmHg on FiO2 = 0.21)&#xD;
&#xD;
          -  Chronic restrictive, obstructive, neuromuscular, chest wall or pulmonary vascular&#xD;
             disease resulting in severe exercise restriction (e.g., unable to climb stairs or&#xD;
             perform household duties), secondary polycythaemia, severe pulmonary hypertension&#xD;
             (mean PAP &gt; 40 mmHg), or ventilator dependency&#xD;
&#xD;
          -  Requirement for urgent/emergent surgery&#xD;
&#xD;
          -  Progressive neuromuscular illness* that will result in prolonged need for mechanical&#xD;
             ventilation&#xD;
&#xD;
          -  Previous randomization in this trial&#xD;
&#xD;
          -  Consent refusal&#xD;
&#xD;
          -  Surgeon, anesthesiologist, intensivist refusal&#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_official>
    <last_name>Matteo Parotto, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Toronto General Hospital, UHN</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Matteo Parotto, MD, PhD</last_name>
    <phone>416-340-4800</phone>
    <phone_ext>5877</phone_ext>
    <email>matteo.parotto@uhn.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Toronto General Hospital, University Health Network</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2C4</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Matteo Parotto, MD</last_name>
      <phone>416-340-4800</phone>
      <phone_ext>5164</phone_ext>
      <email>matteo.parotto@uhn.ca</email>
    </contact>
    <contact_backup>
      <last_name>Jo Carroll</last_name>
      <phone>416-340-4800</phone>
      <phone_ext>3243</phone_ext>
      <email>jo.carroll@uhn.ca</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>April 29, 2021</last_update_submitted>
  <last_update_submitted_qc>April 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Health Network, Toronto</investigator_affiliation>
    <investigator_full_name>Jo Carroll</investigator_full_name>
    <investigator_title>Manager Anesthesia Research</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03288558
org study id: 17-5171
nct id: NCT03288558
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Heart surgery is a life-saving intervention for hundreds of thousands of patients each year
      worldwide. Advances in technology and medical expertise have improved outcomes for these
      patients over the years. However, despite such advances, approximately 30% of patients
      develop lung complications (also called "pulmonary complications") after heart surgery, which
      result in prolonged hospital stay, increased mortality and healthcare costs.

      During and immediately after heart surgery, the patient's breathing needs to be artificially
      controlled by a breathing machine, called "mechanical ventilator". The medical literature has
      reported that in critically ill patients the use of specific settings on the breathing
      machine (so called "protective mechanical ventilation") prevents lung complications and
      significantly decreases mortality. Studies show that such settings could also be beneficial
      for patients that undergo several types of planned surgery, however data regarding heart
      surgery patients (the most vulnerable to lung complications) are lacking.The aim of our study
      is to test whether the use of protective mechanical ventilation settings during and after
      heart surgery reduces lung complications compared to the current standard of care. The main
      innovation of this study is the application of a novel protective mechanical ventilation
      strategy to patients undergoing cardiac surgery, in order to reduce post-operative pulmonary
      complications.
Postoperative pulmonary complications are frequent after cardiac surgery, affecting
      approximately 30% of all patients. Such complications result in increased morbidity,
      mortality and health care utilization. During and immediately after surgery, mechanical
      ventilation is required to control the patient's breathing. Recent scientific literature
      showed the striking importance of specific mechanical ventilation settings (which often
      constituted a bundle of interventions and were generally called "protective mechanical
      ventilation") in other areas of medicine (i.e., critical care, abdominal surgery, management
      of organ donors) to prevent the onset or propagation of lung injury as well as multiple organ
      dysfunction. These protective settings include tidal volume of 6 ml/kg of ideal body weight
      (as opposed to the traditional tidal volume of 10-12 ml/kg), use of positive end expiratory
      pressure (PEEP), recruitment maneuvers (temporary periodic application of higher respiratory
      pressures or volumes on the mechanical ventilator in order to re-open collapsed areas of the
      lungs) and attention at avoiding lung collapse during patient transfer and suctioning (i.e.
      maintaining PEEP during transfer and avoiding disconnection from the breathing circuit during
      suctioning of respiratory secretions). Such interventions could play an even more important
      role during cardiac surgery, where several insults to the lung take place. These insults
      result from the inflammatory cascade triggered by cardiopulmonary bypass (CPB), myocardial
      injury and areas of lung collapse (atelectasis). Indeed, a recent retrospective study showed
      that the tidal volume utilized during and after cardiac surgery impacts significantly on
      organ dysfunction, with a tidal volume less than 10 ml/kg of ideal body weight providing
      better outcomes than larger tidal volumes.

      The investigators hypothesize that our proposed bundle of protective mechanical ventilation
      settings aimed at minimizing lung injury by continuation of mechanical ventilation during
      cardiopulmonary bypass, recruitment maneuvers, and use of systems that prevent lung collapse
      during patient transfer and suctioning (i.e. PEEP valves and closed respiratory circuits)
      will reduce postoperative pulmonary complications compared to the current standard of care,
      hence significantly improving patients outcomes and reducing health care costs.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Outcomes Assessor)
measure: Post-operative pulmonary complications
time frame: for 7 days post operatively
description: Daily chart review and assessment of any pulmonary complications documented
measure: Ventilator free days
time frame: Post op day 1-28 days
description: number of days without a ventilator
Number of days without ventilation
measure: Intensive care length of stay
time frame: Post op day 1-28 days
description: Number of days in the intensive care unit
measure: Hospital length of stay
time frame: Post op day 1-28 days
description: Number of days in the hospital
measure: Duration of mechanical ventilation
time frame: Post op day 1-28 days
description: Length of time on a ventilator
measure: Ease of surgical access
time frame: Intraoperatively during surgery
description: Ability of the surgeon to access the surgical field during cardiopulmonary bypass using a 5 point Likert scale
measure: Barotrauma
time frame: in the first 7 days after surgery
description: defined as radiological evidence of pneumothorax and/or pneumomediastinum
measure: Surgical complications
time frame: From the day of surgery to 48 hours post surgery
description: death, myocardial infarction, stroke, acute liver injury, and chest reopening
measure: Acute Kidney Injury
time frame: Day of surgery to 28 days
description: Incidence of Acute Kidney Injury across the study population
measure: Mortality
time frame: Day of surgery to 90-day
description: Incidence of mortality across the study population
measure: Home and alive
time frame: up to 30 days after surgery
description: to evaluate days at home
arm group label: Intervention Group
arm group type: Experimental
description: Subjects randomized to the intervention group will receive a comprehensive perioperative mechanical ventilation strategy that includes a bundle of protective settings (use of PEEP, recruitment maneuvers and continuation of mechanical ventilation during CPB).
arm group label: Control Group
arm group type: No Intervention
description: Subjects randomized to the control group will receive mechanical ventilation according to the current usual care.
intervention type: Other
intervention name: A comprehensive perioperative mechanical ventilation strategy
description: 1) Intervention group.
Recruitment maneuvers (doubling the tidal volumes for 10 consecutive breaths) every 30min and after every time mechanical ventilation is stopped for surgical reasons, suctioning occurs or the breathing circuit is disconnected
Mechanical ventilation will be continued during CPB (PEEP 5 cm H2O, respiratory rate 8/min, Tidal Volume 6 ml/kg PBW, FiO2 21%
Avoidance of lung de-recruitment during patient's transfer (use of PEEP via PEEP valves, endotracheal tube clamps during disconnection from the breathing circuit)
Avoidance of disconnection from respiratory circuit during respiratory secretions suctioning (applying closed suction circuits)
For the remaining aspects the mechanical ventilation settings will be the same as in the control group.
Tidal volume 6ml/kg PBW PEEP 5cm H20 FiO2 to target SatO2 of 92-97% Discontinuation of mechanical ventilation during cardiopulmonary bypass
arm group label: Intervention Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Matteo Parotto, MD, PhD
role: Principal Investigator
affiliation: Toronto General Hospital, UHN
last name: Matteo Parotto, MD, PhD
phone: 416-340-4800
phone ext: 5877
email: matteo.parotto@uhn.ca
facility: 
status: Recruiting
contact: 
contact backup: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University Health Network, Toronto
investigator full name: Jo Carroll
investigator title: Manager Anesthesia Research
sharing ipd: No