<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/NCT01707459</url>
  </required_header>
  <id_info>
    <org_study_id>UHN090090BE</org_study_id>
    <nct_id>NCT01707459</nct_id>
  </id_info>
  <brief_title>The Association Between Platelet Inhibition and Perioperative Major Adverse Cardiac Events In Post-Percutaneous Coronary Intervention (PCI) Patients Undergoing Non-Cardiac Surgery</brief_title>
  <official_title>The Association Between Platelet Inhibition and Perioperative Major Adverse Cardiac Events In Post-Percutaneous Coronary Intervention (PCI) Patients Undergoing Non-Cardiac Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Anesthesia Patient Safety Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Health Network, Toronto</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This prospective, multicentre, observational study aims to test pre-operative platelet&#xD;
      function when taking anti-platelet medications. The investigators are using a simple bedside&#xD;
      blood test called Thromboelastography (TEG) and Platelet Mapping Assay (PMA). The&#xD;
      investigators will then follow the patient throughout their hospital stay for any major&#xD;
      cardiac complications (MACE) after surgery (peri-operative). The investigators hope to&#xD;
      determine if there is an association between how well platelets were inhibited by these drugs&#xD;
      before surgery and MACE during the perioperative period, 30 day, and one year follow-up.&#xD;
      Also, the response of various people to anti-platelet medications and their chances of&#xD;
      getting a major adverse cardiac outcome are determined by their genetic makeup. The&#xD;
      investigators will try to determine if certain genes are associated with higher cardiac risk.&#xD;
&#xD;
      Hypothesis: In patients who had percutaneous coronary intervention (PCI) and are undergoing&#xD;
      non-cardiac surgery (NCS) major adverse cardiac events (MACE) are associated with inadequate&#xD;
      platelet inhibition.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Data analysis: The participants' demographics, preoperative characteristics and postoperative&#xD;
      information will be summarized using descriptive statistics: expressed as mean (standard&#xD;
      deviation) or median (minimum, maximum, interquartile range) for continuous variables and&#xD;
      number (percent) for categorical variables. We will initially use restricted cubic spline&#xD;
      plots to evaluate the nature of the association of platelet inhibition (continuous variable)&#xD;
      and the risk of MACE (logit transformation). Based upon these results, we will determine if&#xD;
      percent inhibition can be treated as a continuous variable, or whether it can be categorized&#xD;
      along specific cut-offs. We will also compare these results against a&#xD;
      receiver-operating-characteristic curve analysis. Once we have determined the appropriate&#xD;
      approach for describing percent platelet inhibition, univariate analyses will be performed&#xD;
      with chi-square or Fishers' exact test for categorical data, and t-test and Mann-Whitney U&#xD;
      test for continuous data. A p &lt; 0.05 will be considered statistically significant. Random&#xD;
      effect multivariable logistic regression will be used to assess the adjusted association of&#xD;
      platelet inhibition with MACE during the perioperative period.46 This regression model will&#xD;
      employ a random intercept for each center, so as to minimize the bias due to any confounding&#xD;
      by center.47 Regression models will be constructed to selectively include the potentially&#xD;
      confounding perioperative variables that are associated with a higher risk of MACE (as&#xD;
      identified from the literature and clinical experience).7-12 In addition to platelet&#xD;
      inhibition (preoperative value or change), four covariates will be included in the model:&#xD;
      type of stent; time between PCI and NCS; mono-, dual (aspirin or aspirin and clopidogrel) or&#xD;
      no therapy until the day of surgery; and urgent surgery. Since the recommended range of&#xD;
      platelet inhibition (20-50%)was never validated during the perioperative period we will&#xD;
      describe it as a continuous variable (0-100%).&#xD;
&#xD;
      Primary analysis will be as per protocol the secondary analysis will include patients who&#xD;
      have incomplete data i.e. discharged early or refused one or more TEG samples.&#xD;
&#xD;
      Sample Size: The sample size estimations were based on comparison of platelet inhibition&#xD;
      (measures as a continuous variable) between individuals who did or did not suffer MACE. We&#xD;
      assumed that the difference between the MACE and non-MACE groups with regard to platelet&#xD;
      inhibition would correspond to a medium Cohen's effect size (0.5 SD; i.e. difference in means&#xD;
      equaling 0.5 of the pooled standard deviation). Based on the assumption of the medium effect&#xD;
      size difference, an expected 20% rate of MACE, a 2-sided alpha of 0.05, 90 % power, and a 10%&#xD;
      dropout rate, we would need 189 patients in total. In addition, since our planned statistical&#xD;
      model involves logistic regression with a total of five covariates (platelet inhibition&#xD;
      value; stent type; emergency surgery; time between PCI and NCS; mono-, dual or no therapy&#xD;
      after PCI [aspirin vs. aspirin and clopidogrel or no medications]) the sample size estimate&#xD;
      would still have approximately 8 events per included covariate in the regression model. To&#xD;
      minimize bias in the regression model, estimates recommend the minimum number of outcomes per&#xD;
      covariate is 5-10.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2010</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">August 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with major adverse cardiac event (MACE)</measure>
    <time_frame>Measure will occure every day for 5 postoperative days</time_frame>
    <description>ECG daily for five days postoperatively Troponin measurements every 8 h +/- 1h for 6 measurements (first 48 hours postoperatively) then once daily till the fifth postoperative day.&#xD;
Patients will be assessed daily by study personnel for the presence of MACE (defined as death, ST or non-ST elevation myocardial infarction [MI], stent thrombosis or the need for repeat revascularization [PCI or coronary artery bypass grafting]transfusions, or the presence of bleeding complications.</description>
  </primary_outcome>
  <enrollment type="Actual">201</enrollment>
  <condition>Thrombosis</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      TEG-PMA and gene polymorphism analysis on blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients who have coronary stents and undergoing non-cardiac surgery&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Scheduled for non-cardiac surgery&#xD;
&#xD;
          -  Has had PCI with: BMS within the last 24 months OR DES within any time frame&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Lack of informed consent&#xD;
&#xD;
          -  Known clotting abnormality affecting any part of the clotting cascade&#xD;
&#xD;
          -  Liver dysfunction with co-existing thrombocytopenia or INR &gt; 1.4&#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>Marcin Wasowicz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Toronto General Hospital, University Health Network</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Toronto General Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2015</verification_date>
  <study_first_submitted>December 12, 2011</study_first_submitted>
  <study_first_submitted_qc>October 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 16, 2012</study_first_posted>
  <last_update_submitted>June 17, 2015</last_update_submitted>
  <last_update_submitted_qc>June 17, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 18, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>platelet function</keyword>
  <keyword>perioperative complications</keyword>
  <keyword>major adverse cardiac events (MACE)</keyword>
  <keyword>thromboelastography</keyword>
  <keyword>polymorphism analysis</keyword>
  <keyword>coronary stents</keyword>
  <keyword>non-cardiac surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Cardiovascular Diseases</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/NCT01707459
org study id: UHN090090BE
nct id: NCT01707459
lead sponsor: 
collaborator: 
has dmc: No
This prospective, multicentre, observational study aims to test pre-operative platelet
      function when taking anti-platelet medications. The investigators are using a simple bedside
      blood test called Thromboelastography (TEG) and Platelet Mapping Assay (PMA). The
      investigators will then follow the patient throughout their hospital stay for any major
      cardiac complications (MACE) after surgery (peri-operative). The investigators hope to
      determine if there is an association between how well platelets were inhibited by these drugs
      before surgery and MACE during the perioperative period, 30 day, and one year follow-up.
      Also, the response of various people to anti-platelet medications and their chances of
      getting a major adverse cardiac outcome are determined by their genetic makeup. The
      investigators will try to determine if certain genes are associated with higher cardiac risk.

      Hypothesis: In patients who had percutaneous coronary intervention (PCI) and are undergoing
      non-cardiac surgery (NCS) major adverse cardiac events (MACE) are associated with inadequate
      platelet inhibition.
Data analysis: The participants' demographics, preoperative characteristics and postoperative
      information will be summarized using descriptive statistics: expressed as mean (standard
      deviation) or median (minimum, maximum, interquartile range) for continuous variables and
      number (percent) for categorical variables. We will initially use restricted cubic spline
      plots to evaluate the nature of the association of platelet inhibition (continuous variable)
      and the risk of MACE (logit transformation). Based upon these results, we will determine if
      percent inhibition can be treated as a continuous variable, or whether it can be categorized
      along specific cut-offs. We will also compare these results against a
      receiver-operating-characteristic curve analysis. Once we have determined the appropriate
      approach for describing percent platelet inhibition, univariate analyses will be performed
      with chi-square or Fishers' exact test for categorical data, and t-test and Mann-Whitney U
      test for continuous data. A p < 0.05 will be considered statistically significant. Random
      effect multivariable logistic regression will be used to assess the adjusted association of
      platelet inhibition with MACE during the perioperative period.46 This regression model will
      employ a random intercept for each center, so as to minimize the bias due to any confounding
      by center.47 Regression models will be constructed to selectively include the potentially
      confounding perioperative variables that are associated with a higher risk of MACE (as
      identified from the literature and clinical experience).7-12 In addition to platelet
      inhibition (preoperative value or change), four covariates will be included in the model:
      type of stent; time between PCI and NCS; mono-, dual (aspirin or aspirin and clopidogrel) or
      no therapy until the day of surgery; and urgent surgery. Since the recommended range of
      platelet inhibition (20-50%)was never validated during the perioperative period we will
      describe it as a continuous variable (0-100%).

      Primary analysis will be as per protocol the secondary analysis will include patients who
      have incomplete data i.e. discharged early or refused one or more TEG samples.

      Sample Size: The sample size estimations were based on comparison of platelet inhibition
      (measures as a continuous variable) between individuals who did or did not suffer MACE. We
      assumed that the difference between the MACE and non-MACE groups with regard to platelet
      inhibition would correspond to a medium Cohen's effect size (0.5 SD; i.e. difference in means
      equaling 0.5 of the pooled standard deviation). Based on the assumption of the medium effect
      size difference, an expected 20% rate of MACE, a 2-sided alpha of 0.05, 90 % power, and a 10%
      dropout rate, we would need 189 patients in total. In addition, since our planned statistical
      model involves logistic regression with a total of five covariates (platelet inhibition
      value; stent type; emergency surgery; time between PCI and NCS; mono-, dual or no therapy
      after PCI [aspirin vs. aspirin and clopidogrel or no medications]) the sample size estimate
      would still have approximately 8 events per included covariate in the regression model. To
      minimize bias in the regression model, estimates recommend the minimum number of outcomes per
      covariate is 5-10.
observational model: Cohort
time perspective: Prospective
measure: Number of patients with major adverse cardiac event (MACE)
time frame: Measure will occure every day for 5 postoperative days
description: ECG daily for five days postoperatively Troponin measurements every 8 h +/- 1h for 6 measurements (first 48 hours postoperatively) then once daily till the fifth postoperative day.
Patients will be assessed daily by study personnel for the presence of MACE (defined as death, ST or non-ST elevation myocardial infarction [MI], stent thrombosis or the need for repeat revascularization [PCI or coronary artery bypass grafting]transfusions, or the presence of bleeding complications.
TEG-PMA and gene polymorphism analysis on blood samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marcin Wasowicz, MD
role: Principal Investigator
affiliation: Toronto General Hospital, University Health Network
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Thrombosis
mesh term: Cardiovascular Diseases