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/NCT05964374</url>
    </required_header>
    <id_info>
      <org_study_id>REB23-0043</org_study_id>
      <nct_id>NCT05964374</nct_id>
    </id_info>
    <brief_title>Goal-Directed Therapy Following Cardiac Surgery</brief_title>
    <official_title>Goal-Directed Therapy (GDT) Using Hypotension Prediction Index (HPI) Following Cardiac Surgery: a Pilot Randomized Control Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Calgary</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University of Alberta</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Calgary</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Pilot prospective randomized control trial comparing goal-directed therapy algorithm vs&#xD;
        routine care in the intensive care unit following cardiac surgery.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Rationale:&#xD;
  &#xD;
        Goal-directed therapy (GDT) has been shown to reduce complications and length of stay on&#xD;
        cardiac surgery patients. Unfortunately, the existing literature on GDT in CV surgery has&#xD;
        several limitations, which creates uncertainty over the expected benefit of implementing this&#xD;
        care element with high associated costs and impact on workflow. Hypotension Prediction Index&#xD;
        (HPI) is a proprietary algorithm that utilizes pulse contour analysis from invasive arterial&#xD;
        pressure monitoring to identify patients at risk for becoming hypotensive within 15 minutes.&#xD;
        The algorithm was developed using machine learning on a large surgical/ICU data set, and then&#xD;
        externally validated on non-cardiac and cardiac surgical patients. HPI, as part of a GDT&#xD;
        algorithm, may allow healthcare providers to identify patients recovering from cardiac&#xD;
        surgery who may benefit from optimization prior to becoming hypotensive and assist with&#xD;
        selecting the most appropriate hemodynamic intervention.&#xD;
  &#xD;
        Hypothesis:&#xD;
  &#xD;
        Application of an HPI-based GDT algorithm will result in a difference in cumulative fluid&#xD;
        administration over the first 24-hours of index ICU admission following cardiac surgery.&#xD;
  &#xD;
        Study Design:&#xD;
  &#xD;
        Unblinded randomized controlled trial pilot. Data will be used to inform/justify the&#xD;
        feasibility, design, and implementation of a future multi-center randomized controlled trial.&#xD;
  &#xD;
        Study Population:&#xD;
  &#xD;
        Moderate or high-risk (EuroSCORE II &gt; 2%), non-emergent, adult open-heart cardiac surgery&#xD;
        patients. Heart transplant, durable VAD implantation, or patients who require post-operative&#xD;
        MCS support will be excluded.&#xD;
  &#xD;
        Sample size= 100 (50 control : 50 intervention)&#xD;
  &#xD;
        Intervention:&#xD;
  &#xD;
        Patients randomized to the intervention arm will be monitored using the HPI technology and be&#xD;
        treated following a GDT algorithm when HPI is &gt;50 for 48-hours or duration of invasive&#xD;
        arterial monitoring (whichever occurs first). The GDT algorithm is a standardized approach to&#xD;
        identifying abnormal hemodynamic parameters and administering a prescribed therapy in a&#xD;
        step-wise fashion with fixed re-assessment intervals (see attached).&#xD;
  &#xD;
        What will be different from routine care? :&#xD;
  &#xD;
          1. Hemodynamic interventions (fluid, inotropic, or vasopressor therapy) will be&#xD;
             administered when HPI &gt; 50 rather than MAP &lt; 65.&#xD;
  &#xD;
          2. Choice of applied therapy (fluid, inotropic, or vasopressor therapy) will be guided by a&#xD;
             GDT algorithm.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">July 2023</start_date>
    <completion_date type="Anticipated">June 2024</completion_date>
    <primary_completion_date type="Anticipated">January 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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>24-hour cumulative IV fluid administration</measure>
      <time_frame>24-hours</time_frame>
      <description>Cumulative post-operative intravenous fluid administration over the first 24-hours of index ICU admission.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Fluid Administration</measure>
      <time_frame>Duration of ICU stay, up to 30-days</time_frame>
      <description>Daily average</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fluid Administration</measure>
      <time_frame>Duration of ICU stay, up to 30-days</time_frame>
      <description>Cumulative</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Vasoactive medication administration</measure>
      <time_frame>Duration of ICU stay, up to 30-days</time_frame>
      <description>Daily average</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Vasoactive medication administration</measure>
      <time_frame>Duration of ICU stay, up to 30-days</time_frame>
      <description>Daily cumulative</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Vasoactive medication administration</measure>
      <time_frame>Duration of ICU stay, up to 30-days</time_frame>
      <description>Duration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemodynamic parameters</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>Incidence of HPI &gt; 50 greater than 5-minutes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemodynamic parameters</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>Incidence of HPI &gt; 85 greater than 5-minutes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemodynamic parameters</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>Incidence of MAP &lt; 65 greater than 5-minutes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemodynamic parameters</measure>
      <time_frame>24-hours</time_frame>
      <description>Total Area Under the Curve (AUC) for HPI &gt; 50</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemodynamic parameters</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>Total Area Under the Curve (AUC) for HPI &gt; 50</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemodynamic parameters</measure>
      <time_frame>24-hours</time_frame>
      <description>Total Area Under the Curve (AUC) for HPI &gt; 85</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemodynamic parameters</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>Total Area Under the Curve (AUC) for HPI &gt; 85</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemodynamic parameters</measure>
      <time_frame>24-hours</time_frame>
      <description>Total Area Under the Curve (AUC) for MAP &lt; 65</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemodynamic parameters</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>Total Area Under the Curve (AUC) for MAP &lt; 65</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Enrollment</measure>
      <time_frame>1-year</time_frame>
      <description>Proportion of screened patients eligible for enrollment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Enrollment</measure>
      <time_frame>1-year</time_frame>
      <description>Proportion of eligible patients who consent to participate.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Study Protocol Compliance</measure>
      <time_frame>1-year</time_frame>
      <description>Proportion of consented patients who complete all study assessments.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Arterial Monitoring Reliability</measure>
      <time_frame>1-year</time_frame>
      <description>Number of arterial catheters requiring replacement</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>GDT algorithm compliance</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>Time from HPI &gt; 50 to application of an intervention</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>GDT algorithm compliance</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>Proportion of hemodynamic interventions applied for HPI &gt; 50 that were recommended by the algorithm</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>GDT algorithm compliance</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>Proportion of hemodynamic interventions applied for MAP &lt; 65 that would be recommended by the algorithm based on hemodynamic parameters.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>GDT algorithm compliance</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>MD notifications prompted by the GDT algorithm and resulting actions</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>GDT algorithm compliance</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>Actions (therapies or investigations) prompted by an MD notification.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>GDT algorithm compliance</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>Number of study protocol suspensions</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>GDT algorithm compliance</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>Duration of protocol suspensions</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>GDT algorithm compliance</measure>
      <time_frame>48-hours or when arterial line removed</time_frame>
      <description>Rationale for protocol suspensions</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>End-organ dysfunction/injury</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Acute kidney injury</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>End-organ dysfunction/injury</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Delirium</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>End-organ dysfunction/injury</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Stroke</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>End-organ dysfunction/injury</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Ileus</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>End-organ dysfunction/injury</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Gut infarction</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>End-organ dysfunction/injury</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Prolonged mechanical ventilation (&gt; 24 hours)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>End-organ dysfunction/injury</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Deep sternal wound infection</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>End-organ dysfunction/injury</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Any surgical site infection</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Transfusion</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Total red-blood cell administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Transfusion</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Total fresh-frozen plasma administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Transfusion</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Total platelet administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Transfusion</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Total albumin administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mobilzation</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Time to first mobilization (dangle)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mobilzation</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Time to first mobilization (stand)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mobilization</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Time to first mobilization (walk)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hydration</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Time to first PO hydration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Nutrition</measure>
      <time_frame>Index admission, up to 30-days</time_frame>
      <description>Time to first PO nutrition</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Patient-centered Outcome</measure>
      <time_frame>Index admission, up to 10-days</time_frame>
      <description>Quality of Recovery-15 (QOR-15) at post-op days 3, 5, 7, and 10.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Patient-centered Outcome</measure>
      <time_frame>Up to 1-year post-operative</time_frame>
      <description>World Health Organization Disability Assessment Schedule (WHODAS 2.0) at baseline, 2-weeks, 30-days, 90-days, and 1-year.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Patient-centered Outcome</measure>
      <time_frame>Up to 1-year post-operative</time_frame>
      <description>MacNew Questionnaire at baseline, 2-weeks, 30-days, 90-days, and 1-year.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Patient-centered Outcome</measure>
      <time_frame>Up to 1-year post-operative</time_frame>
      <description>The Depression, Anxiety and Stress Scale - 21 Items (DASS-21) at baseline, 2-weeks, 30-days, 90-days, and 1-year.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Patient-centered Outcome</measure>
      <time_frame>30-days</time_frame>
      <description>Canadian Patient Experiences Survey on Inpatient Care (CPES-IC) at 30-days</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Length of Stay</measure>
      <time_frame>Up to 1-year post-operative</time_frame>
      <description>ICU length of stay</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Length of Stay</measure>
      <time_frame>Up to 1-year post-operative</time_frame>
      <description>Hospital length of stay</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Re-admission</measure>
      <time_frame>30-days</time_frame>
      <description>Incidence of hospital re-admission within 30-days of index surgery</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mortality</measure>
      <time_frame>Up to 1-year post-operative</time_frame>
      <description>7-day, 30-day, and 1-year mortality.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Surgery</condition>
    <arm_group>
      <arm_group_label>Control</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Routine post-operative clinical care.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Intervention</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Goal-directed therapy algorithm in addition to routine post-operative clinical care.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Goal-directed therapy</intervention_name>
      <description>Goal-directed therapy using HemoSphere® monitor, Acumen® transducer, and Hypotension Prediction Index® algorithm (Edwards Lifesciences, Irvine, USA),</description>
      <arm_group_label>Intervention</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. ≥ 18 years of age&#xD;
  &#xD;
            2. Planned cardiac surgery using cardiopulmonary bypass (sternotomy or MICS)&#xD;
  &#xD;
            3. Preoperative European System for Cardiac Operative Risk Evaluation II (EuroSCORE II)&#xD;
               of 2% or more.&#xD;
  &#xD;
            4. Informed consent obtained.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients who refuse participation&#xD;
  &#xD;
            2. Patients who are unable to give informed consent&#xD;
  &#xD;
            3. Patients who are having a heart transplant or having surgery solely for an insertion&#xD;
               of a ventricular assist device&#xD;
  &#xD;
            4. Emergency surgery&#xD;
  &#xD;
            5. Patients who require MCS (including ECMO, Impella, or IABP) post-operatively&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>99 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <reference>
      <citation>Li P, Qu LP, Qi D, Shen B, Wang YM, Xu JR, Jiang WH, Zhang H, Ding XQ, Teng J. Significance of perioperative goal-directed hemodynamic approach in preventing postoperative complications in patients after cardiac surgery: a meta-analysis and systematic review. Ann Med. 2017 Jun;49(4):343-351. doi: 10.1080/07853890.2016.1271956. Epub 2017 Feb 2.</citation>
      <PMID>27936959</PMID>
    </reference>
    <reference>
      <citation>Osawa EA, Rhodes A, Landoni G, Galas FR, Fukushima JT, Park CH, Almeida JP, Nakamura RE, Strabelli TM, Pileggi B, Leme AC, Fominskiy E, Sakr Y, Lima M, Franco RA, Chan RP, Piccioni MA, Mendes P, Menezes SR, Bruno T, Gaiotto FA, Lisboa LA, Dallan LA, Hueb AC, Pomerantzeff PM, Kalil Filho R, Jatene FB, Auler Junior JO, Hajjar LA. Effect of Perioperative Goal-Directed Hemodynamic Resuscitation Therapy on Outcomes Following Cardiac Surgery: A Randomized Clinical Trial and Systematic Review. Crit Care Med. 2016 Apr;44(4):724-33. doi: 10.1097/CCM.0000000000001479.</citation>
      <PMID>26646462</PMID>
    </reference>
    <reference>
      <citation>Engelman DT, Ben Ali W, Williams JB, Perrault LP, Reddy VS, Arora RC, Roselli EE, Khoynezhad A, Gerdisch M, Levy JH, Lobdell K, Fletcher N, Kirsch M, Nelson G, Engelman RM, Gregory AJ, Boyle EM. Guidelines for Perioperative Care in Cardiac Surgery: Enhanced Recovery After Surgery Society Recommendations. JAMA Surg. 2019 Aug 1;154(8):755-766. doi: 10.1001/jamasurg.2019.1153.</citation>
      <PMID>31054241</PMID>
    </reference>
    <reference>
      <citation>Hatib F, Jian Z, Buddi S, Lee C, Settels J, Sibert K, Rinehart J, Cannesson M. Machine-learning Algorithm to Predict Hypotension Based on High-fidelity Arterial Pressure Waveform Analysis. Anesthesiology. 2018 Oct;129(4):663-674. doi: 10.1097/ALN.0000000000002300.</citation>
      <PMID>29894315</PMID>
    </reference>
    <reference>
      <citation>Davies SJ, Vistisen ST, Jian Z, Hatib F, Scheeren TWL. Ability of an Arterial Waveform Analysis-Derived Hypotension Prediction Index to Predict Future Hypotensive Events in Surgical Patients. Anesth Analg. 2020 Feb;130(2):352-359. doi: 10.1213/ANE.0000000000004121. Erratum In: Anesth Analg. 2023 Sep 1;137(3):e33.</citation>
      <PMID>30896602</PMID>
    </reference>
    <reference>
      <citation>Shin B, Maler SA, Reddy K, Fleming NW. Use of the Hypotension Prediction Index During Cardiac Surgery. J Cardiothorac Vasc Anesth. 2021 Jun;35(6):1769-1775. doi: 10.1053/j.jvca.2020.12.025. Epub 2020 Dec 21.</citation>
      <PMID>33446404</PMID>
    </reference>
    <reference>
      <citation>Parsons H, Zilahi G. Pro: Hypotension Prediction Index-A New Tool to Predict Hypotension in Cardiac Surgery? J Cardiothorac Vasc Anesth. 2023 Oct;37(10):2133-2136. doi: 10.1053/j.jvca.2023.05.023. Epub 2023 May 17. No abstract available.</citation>
      <PMID>37301700</PMID>
    </reference>
    <reference>
      <citation>Rellum SR, Schuurmans J, Schenk J, van der Ster BJP, van der Ven WH, Geerts BF, Hollmann MW, Cherpanath TGV, Lagrand WK, Wynandts P, Paulus F, Driessen AHG, Terwindt LE, Eberl S, Hermanns H, Veelo DP, Vlaar APJ. Effect of the machine learning-derived Hypotension Prediction Index (HPI) combined with diagnostic guidance versus standard care on depth and duration of intraoperative and postoperative hypotension in elective cardiac surgery patients: HYPE-2 - study protocol of a randomised clinical trial. BMJ Open. 2023 May 2;13(5):e061832. doi: 10.1136/bmjopen-2022-061832.</citation>
      <PMID>37130670</PMID>
    </reference>
    <reference>
      <citation>Maheshwari K, Buddi S, Jian Z, Settels J, Shimada T, Cohen B, Sessler DI, Hatib F. Performance of the Hypotension Prediction Index with non-invasive arterial pressure waveforms in non-cardiac surgical patients. J Clin Monit Comput. 2021 Feb;35(1):71-78. doi: 10.1007/s10877-020-00463-5. Epub 2020 Jan 27.</citation>
      <PMID>31989416</PMID>
    </reference>
    <reference>
      <citation>Baumgarten M, Brodsgaard A, Bunkenborg G, Foss NB, Norholm V. Nurse and Physician Perceptions of Working With Goal-Directed Therapy in the Perioperative Period. J Perianesth Nurs. 2020 Apr;35(2):198-205. doi: 10.1016/j.jopan.2019.09.005. Epub 2019 Dec 13.</citation>
      <PMID>31843240</PMID>
    </reference>
    <verification_date>June 2023</verification_date>
    <study_first_submitted>June 21, 2023</study_first_submitted>
    <study_first_submitted_qc>July 19, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>July 19, 2023</last_update_submitted>
    <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 27, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>cardiac surgery</keyword>
    <keyword>hemodynamic optimization</keyword>
    <keyword>goal-directed therapy</keyword>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT05964374
  org study id: REB23-0043
  nct id: NCT05964374
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Pilot prospective randomized control trial comparing goal-directed therapy algorithm vs
        routine care in the intensive care unit following cardiac surgery.
  Rationale:
  
        Goal-directed therapy (GDT) has been shown to reduce complications and length of stay on
        cardiac surgery patients. Unfortunately, the existing literature on GDT in CV surgery has
        several limitations, which creates uncertainty over the expected benefit of implementing this
        care element with high associated costs and impact on workflow. Hypotension Prediction Index
        (HPI) is a proprietary algorithm that utilizes pulse contour analysis from invasive arterial
        pressure monitoring to identify patients at risk for becoming hypotensive within 15 minutes.
        The algorithm was developed using machine learning on a large surgical/ICU data set, and then
        externally validated on non-cardiac and cardiac surgical patients. HPI, as part of a GDT
        algorithm, may allow healthcare providers to identify patients recovering from cardiac
        surgery who may benefit from optimization prior to becoming hypotensive and assist with
        selecting the most appropriate hemodynamic intervention.
  
        Hypothesis:
  
        Application of an HPI-based GDT algorithm will result in a difference in cumulative fluid
        administration over the first 24-hours of index ICU admission following cardiac surgery.
  
        Study Design:
  
        Unblinded randomized controlled trial pilot. Data will be used to inform/justify the
        feasibility, design, and implementation of a future multi-center randomized controlled trial.
  
        Study Population:
  
        Moderate or high-risk (EuroSCORE II > 2%), non-emergent, adult open-heart cardiac surgery
        patients. Heart transplant, durable VAD implantation, or patients who require post-operative
        MCS support will be excluded.
  
        Sample size= 100 (50 control : 50 intervention)
  
        Intervention:
  
        Patients randomized to the intervention arm will be monitored using the HPI technology and be
        treated following a GDT algorithm when HPI is >50 for 48-hours or duration of invasive
        arterial monitoring (whichever occurs first). The GDT algorithm is a standardized approach to
        identifying abnormal hemodynamic parameters and administering a prescribed therapy in a
        step-wise fashion with fixed re-assessment intervals (see attached).
  
        What will be different from routine care? :
  
          1. Hemodynamic interventions (fluid, inotropic, or vasopressor therapy) will be
             administered when HPI > 50 rather than MAP < 65.
  
          2. Choice of applied therapy (fluid, inotropic, or vasopressor therapy) will be guided by a
             GDT algorithm.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  measure: 24-hour cumulative IV fluid administration
  time frame: 24-hours
  description: Cumulative post-operative intravenous fluid administration over the first 24-hours of index ICU admission.
  measure: Fluid Administration
  time frame: Duration of ICU stay, up to 30-days
  description: Daily average
  measure: Fluid Administration
  time frame: Duration of ICU stay, up to 30-days
  description: Cumulative
  measure: Vasoactive medication administration
  time frame: Duration of ICU stay, up to 30-days
  description: Daily average
  measure: Vasoactive medication administration
  time frame: Duration of ICU stay, up to 30-days
  description: Daily cumulative
  measure: Vasoactive medication administration
  time frame: Duration of ICU stay, up to 30-days
  description: Duration
  measure: Hemodynamic parameters
  time frame: 48-hours or when arterial line removed
  description: Incidence of HPI > 50 greater than 5-minutes
  measure: Hemodynamic parameters
  time frame: 48-hours or when arterial line removed
  description: Incidence of HPI > 85 greater than 5-minutes
  measure: Hemodynamic parameters
  time frame: 48-hours or when arterial line removed
  description: Incidence of MAP < 65 greater than 5-minutes
  measure: Hemodynamic parameters
  time frame: 24-hours
  description: Total Area Under the Curve (AUC) for HPI > 50
  measure: Hemodynamic parameters
  time frame: 48-hours or when arterial line removed
  description: Total Area Under the Curve (AUC) for HPI > 50
  measure: Hemodynamic parameters
  time frame: 24-hours
  description: Total Area Under the Curve (AUC) for HPI > 85
  measure: Hemodynamic parameters
  time frame: 48-hours or when arterial line removed
  description: Total Area Under the Curve (AUC) for HPI > 85
  measure: Hemodynamic parameters
  time frame: 24-hours
  description: Total Area Under the Curve (AUC) for MAP < 65
  measure: Hemodynamic parameters
  time frame: 48-hours or when arterial line removed
  description: Total Area Under the Curve (AUC) for MAP < 65
  measure: Enrollment
  time frame: 1-year
  description: Proportion of screened patients eligible for enrollment.
  measure: Enrollment
  time frame: 1-year
  description: Proportion of eligible patients who consent to participate.
  measure: Study Protocol Compliance
  time frame: 1-year
  description: Proportion of consented patients who complete all study assessments.
  measure: Arterial Monitoring Reliability
  time frame: 1-year
  description: Number of arterial catheters requiring replacement
  measure: GDT algorithm compliance
  time frame: 48-hours or when arterial line removed
  description: Time from HPI > 50 to application of an intervention
  measure: GDT algorithm compliance
  time frame: 48-hours or when arterial line removed
  description: Proportion of hemodynamic interventions applied for HPI > 50 that were recommended by the algorithm
  measure: GDT algorithm compliance
  time frame: 48-hours or when arterial line removed
  description: Proportion of hemodynamic interventions applied for MAP < 65 that would be recommended by the algorithm based on hemodynamic parameters.
  measure: GDT algorithm compliance
  time frame: 48-hours or when arterial line removed
  description: MD notifications prompted by the GDT algorithm and resulting actions
  measure: GDT algorithm compliance
  time frame: 48-hours or when arterial line removed
  description: Actions (therapies or investigations) prompted by an MD notification.
  measure: GDT algorithm compliance
  time frame: 48-hours or when arterial line removed
  description: Number of study protocol suspensions
  measure: GDT algorithm compliance
  time frame: 48-hours or when arterial line removed
  description: Duration of protocol suspensions
  measure: GDT algorithm compliance
  time frame: 48-hours or when arterial line removed
  description: Rationale for protocol suspensions
  measure: End-organ dysfunction/injury
  time frame: Index admission, up to 30-days
  description: Acute kidney injury
  measure: End-organ dysfunction/injury
  time frame: Index admission, up to 30-days
  description: Delirium
  measure: End-organ dysfunction/injury
  time frame: Index admission, up to 30-days
  description: Stroke
  measure: End-organ dysfunction/injury
  time frame: Index admission, up to 30-days
  description: Ileus
  measure: End-organ dysfunction/injury
  time frame: Index admission, up to 30-days
  description: Gut infarction
  measure: End-organ dysfunction/injury
  time frame: Index admission, up to 30-days
  description: Prolonged mechanical ventilation (> 24 hours)
  measure: End-organ dysfunction/injury
  time frame: Index admission, up to 30-days
  description: Deep sternal wound infection
  measure: End-organ dysfunction/injury
  time frame: Index admission, up to 30-days
  description: Any surgical site infection
  measure: Transfusion
  time frame: Index admission, up to 30-days
  description: Total red-blood cell administration
  measure: Transfusion
  time frame: Index admission, up to 30-days
  description: Total fresh-frozen plasma administration
  measure: Transfusion
  time frame: Index admission, up to 30-days
  description: Total platelet administration
  measure: Transfusion
  time frame: Index admission, up to 30-days
  description: Total albumin administration
  measure: Mobilzation
  time frame: Index admission, up to 30-days
  description: Time to first mobilization (dangle)
  measure: Mobilzation
  time frame: Index admission, up to 30-days
  description: Time to first mobilization (stand)
  measure: Mobilization
  time frame: Index admission, up to 30-days
  description: Time to first mobilization (walk)
  measure: Hydration
  time frame: Index admission, up to 30-days
  description: Time to first PO hydration
  measure: Nutrition
  time frame: Index admission, up to 30-days
  description: Time to first PO nutrition
  measure: Patient-centered Outcome
  time frame: Index admission, up to 10-days
  description: Quality of Recovery-15 (QOR-15) at post-op days 3, 5, 7, and 10.
  measure: Patient-centered Outcome
  time frame: Up to 1-year post-operative
  description: World Health Organization Disability Assessment Schedule (WHODAS 2.0) at baseline, 2-weeks, 30-days, 90-days, and 1-year.
  measure: Patient-centered Outcome
  time frame: Up to 1-year post-operative
  description: MacNew Questionnaire at baseline, 2-weeks, 30-days, 90-days, and 1-year.
  measure: Patient-centered Outcome
  time frame: Up to 1-year post-operative
  description: The Depression, Anxiety and Stress Scale - 21 Items (DASS-21) at baseline, 2-weeks, 30-days, 90-days, and 1-year.
  measure: Patient-centered Outcome
  time frame: 30-days
  description: Canadian Patient Experiences Survey on Inpatient Care (CPES-IC) at 30-days
  measure: Length of Stay
  time frame: Up to 1-year post-operative
  description: ICU length of stay
  measure: Length of Stay
  time frame: Up to 1-year post-operative
  description: Hospital length of stay
  measure: Re-admission
  time frame: 30-days
  description: Incidence of hospital re-admission within 30-days of index surgery
  measure: Mortality
  time frame: Up to 1-year post-operative
  description: 7-day, 30-day, and 1-year mortality.
  arm group label: Control
  arm group type: No Intervention
  description: Routine post-operative clinical care.
  arm group label: Intervention
  arm group type: Experimental
  description: Goal-directed therapy algorithm in addition to routine post-operative clinical care.
  intervention type: Device
  intervention name: Goal-directed therapy
  description: Goal-directed therapy using HemoSphere® monitor, Acumen® transducer, and Hypotension Prediction Index® algorithm (Edwards Lifesciences, Irvine, USA),
  arm group label: Intervention
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 99 Years
  healthy volunteers: No
  citation: Li P, Qu LP, Qi D, Shen B, Wang YM, Xu JR, Jiang WH, Zhang H, Ding XQ, Teng J. Significance of perioperative goal-directed hemodynamic approach in preventing postoperative complications in patients after cardiac surgery: a meta-analysis and systematic review. Ann Med. 2017 Jun;49(4):343-351. doi: 10.1080/07853890.2016.1271956. Epub 2017 Feb 2.
  PMID: 27936959
  citation: Osawa EA, Rhodes A, Landoni G, Galas FR, Fukushima JT, Park CH, Almeida JP, Nakamura RE, Strabelli TM, Pileggi B, Leme AC, Fominskiy E, Sakr Y, Lima M, Franco RA, Chan RP, Piccioni MA, Mendes P, Menezes SR, Bruno T, Gaiotto FA, Lisboa LA, Dallan LA, Hueb AC, Pomerantzeff PM, Kalil Filho R, Jatene FB, Auler Junior JO, Hajjar LA. Effect of Perioperative Goal-Directed Hemodynamic Resuscitation Therapy on Outcomes Following Cardiac Surgery: A Randomized Clinical Trial and Systematic Review. Crit Care Med. 2016 Apr;44(4):724-33. doi: 10.1097/CCM.0000000000001479.
  PMID: 26646462
  citation: Engelman DT, Ben Ali W, Williams JB, Perrault LP, Reddy VS, Arora RC, Roselli EE, Khoynezhad A, Gerdisch M, Levy JH, Lobdell K, Fletcher N, Kirsch M, Nelson G, Engelman RM, Gregory AJ, Boyle EM. Guidelines for Perioperative Care in Cardiac Surgery: Enhanced Recovery After Surgery Society Recommendations. JAMA Surg. 2019 Aug 1;154(8):755-766. doi: 10.1001/jamasurg.2019.1153.
  PMID: 31054241
  citation: Hatib F, Jian Z, Buddi S, Lee C, Settels J, Sibert K, Rinehart J, Cannesson M. Machine-learning Algorithm to Predict Hypotension Based on High-fidelity Arterial Pressure Waveform Analysis. Anesthesiology. 2018 Oct;129(4):663-674. doi: 10.1097/ALN.0000000000002300.
  PMID: 29894315
  citation: Davies SJ, Vistisen ST, Jian Z, Hatib F, Scheeren TWL. Ability of an Arterial Waveform Analysis-Derived Hypotension Prediction Index to Predict Future Hypotensive Events in Surgical Patients. Anesth Analg. 2020 Feb;130(2):352-359. doi: 10.1213/ANE.0000000000004121. Erratum In: Anesth Analg. 2023 Sep 1;137(3):e33.
  PMID: 30896602
  citation: Shin B, Maler SA, Reddy K, Fleming NW. Use of the Hypotension Prediction Index During Cardiac Surgery. J Cardiothorac Vasc Anesth. 2021 Jun;35(6):1769-1775. doi: 10.1053/j.jvca.2020.12.025. Epub 2020 Dec 21.
  PMID: 33446404
  citation: Parsons H, Zilahi G. Pro: Hypotension Prediction Index-A New Tool to Predict Hypotension in Cardiac Surgery? J Cardiothorac Vasc Anesth. 2023 Oct;37(10):2133-2136. doi: 10.1053/j.jvca.2023.05.023. Epub 2023 May 17. No abstract available.
  PMID: 37301700
  citation: Rellum SR, Schuurmans J, Schenk J, van der Ster BJP, van der Ven WH, Geerts BF, Hollmann MW, Cherpanath TGV, Lagrand WK, Wynandts P, Paulus F, Driessen AHG, Terwindt LE, Eberl S, Hermanns H, Veelo DP, Vlaar APJ. Effect of the machine learning-derived Hypotension Prediction Index (HPI) combined with diagnostic guidance versus standard care on depth and duration of intraoperative and postoperative hypotension in elective cardiac surgery patients: HYPE-2 - study protocol of a randomised clinical trial. BMJ Open. 2023 May 2;13(5):e061832. doi: 10.1136/bmjopen-2022-061832.
  PMID: 37130670
  citation: Maheshwari K, Buddi S, Jian Z, Settels J, Shimada T, Cohen B, Sessler DI, Hatib F. Performance of the Hypotension Prediction Index with non-invasive arterial pressure waveforms in non-cardiac surgical patients. J Clin Monit Comput. 2021 Feb;35(1):71-78. doi: 10.1007/s10877-020-00463-5. Epub 2020 Jan 27.
  PMID: 31989416
  citation: Baumgarten M, Brodsgaard A, Bunkenborg G, Foss NB, Norholm V. Nurse and Physician Perceptions of Working With Goal-Directed Therapy in the Perioperative Period. J Perianesth Nurs. 2020 Apr;35(2):198-205. doi: 10.1016/j.jopan.2019.09.005. Epub 2019 Dec 13.
  PMID: 31843240
  responsible party type: Sponsor
  sharing ipd: No