<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/NCT01726595</url>
  </required_header>
  <id_info>
    <org_study_id>00030546</org_study_id>
    <nct_id>NCT01726595</nct_id>
  </id_info>
  <brief_title>Ultrasound Measurement of Reactive Hyperemia in Critical Care</brief_title>
  <acronym>URHC</acronym>
  <official_title>Ultrasound Measurement of Reactive Hyperemia in Critical Care: Prognostic and Pathophysiologic Significance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Rochester</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Rochester</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesize that doctors and nurses can undergo a brief period of training&#xD;
      and then use ultrasound to accurately measure blood flow in a forearm artery after a brief&#xD;
      period when this flow is interrupted with a blood pressure cuff, a measurement the&#xD;
      investigators call reactive hyperemia. Reactive hyperemia indicates whether the small blood&#xD;
      vessels in the body are healthy -- lower reactive hyperemia indicates worse small blood&#xD;
      vessel function. When measured by experienced ultrasound experts, low reactive hyperemia&#xD;
      strongly predicts death in critically ill patients with infection (severe sepsis).&#xD;
&#xD;
      The investigators are conducting this study to determine if doctors and nurses, without&#xD;
      specific pre-existing expertise in ultrasound, can be trained to make these measurements&#xD;
      accurately. If so, the investigators will prove that these measurements can be applied&#xD;
      reliably in real-world practice.&#xD;
&#xD;
      The investigators also hypothesize that reactive hyperemia predict the outcomes of illness&#xD;
      not just in patients with severe infection, but in other critically ill patients as well.&#xD;
&#xD;
      Finally, the investigators hypothesize that reduced blood flow after blood pressure cuff&#xD;
      occlusion is linked with other abnormalities of blood, previously identified in critically&#xD;
      ill patients. For example, red blood cells from patients with severe sepsis have been shown&#xD;
      to be stiffer than normal, so they are less able to flow along the small blood vessel&#xD;
      passages of the body. Red blood cells become stiffer when there is a certain type of stress&#xD;
      in the body known as &quot;oxidative stress.&quot;&#xD;
&#xD;
      If the investigators show that low reactive hyperemia, stiff red blood cells, and oxidative&#xD;
      stress are linked, the investigators hope to develop new treatments that reduce oxidative&#xD;
      stress, reduce the stiffness of red blood cells, and in turn improve reactive hyperemia.&#xD;
      Improvements in reactive hyperemia indicate improvements in small blood vessel function.&#xD;
      Better small blood vessel function means better delivery of oxygen throughout the body. The&#xD;
      investigators believe that this will improve outcomes for critically ill patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2013</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2019</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>hospital mortality</measure>
    <time_frame>vital status at hospital discharge, an expected average of 3 weeks</time_frame>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">250</enrollment>
  <condition>Severe Sepsis</condition>
  <condition>Critical Illness</condition>
  <arm_group>
    <arm_group_label>severe sepsis</arm_group_label>
    <description>Patients with severe sepsis or septic shock</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-infected critically ill</arm_group_label>
    <description>Patients with severe non-infectious systemic inflammatory response syndrome</description>
  </arm_group>
  <arm_group>
    <arm_group_label>healthy</arm_group_label>
    <description>healthy volunteers</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood and urine specimens will be obtained within 48 hours of diagnosis of severe sepsis or&#xD;
      severe non-infectious systemic inflammatory response syndrome. Subsequent blood and urine&#xD;
      samples will be obtained 3-5 days after the first set of samples, within 48 hours of ICU&#xD;
      discharge, and within 48 hours of hospital discharge. Samples will analyzed immediately or&#xD;
      stored at -80 degrees celsius until use.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Critically ill Patients:&#xD;
&#xD;
        Patients admitted to University of Rochester Medical Center ICU services with 2 of the 4&#xD;
        systemic inflammatory response syndrome (SIRS) criteria and acute organ dysfunction will be&#xD;
        considered for enrollment.&#xD;
&#xD;
        Healthy Control subjects:&#xD;
&#xD;
        Healthy control subjects &gt;= 18 years of age will be recruited from the University and&#xD;
        Rochester region at large.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients admitted to University of Rochester Medical Center ICU services with 2 of the&#xD;
             4 systemic inflammatory response syndrome (SIRS) criteria and acute organ dysfunction&#xD;
             will be considered for enrollment.&#xD;
&#xD;
          -  Healthy control subjects &gt;= 18 years of age will be recruited from the University and&#xD;
             Rochester region at large.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Critically ill patients:&#xD;
&#xD;
               1. Refusal of patient or designated surrogate decision-maker to provide written&#xD;
                  informed consent, or inability to obtain consent within 48 hours of diagnosis&#xD;
&#xD;
               2. Attending physician refusal&#xD;
&#xD;
               3. Hematocrit (Hct) &lt; 21%&#xD;
&#xD;
               4. Acute bleeding requiring PRBC transfusion&#xD;
&#xD;
               5. History of chronic, dialysis dependent renal failure&#xD;
&#xD;
               6. End-stage liver disease and Child-Pugh Grade C&#xD;
&#xD;
               7. History of organ, bone marrow, or stem cell transplant&#xD;
&#xD;
               8. Pregnancy&#xD;
&#xD;
               9. Cardiac surgery (including ventricular assist device prior to first sample&#xD;
                  collection)&#xD;
&#xD;
              10. Do not resuscitate at screening or plans for withdrawal of life support imminent&#xD;
&#xD;
              11. Suicide attempt or intentional drug overdose;&#xD;
&#xD;
              12. Jehovah's witness&#xD;
&#xD;
          -  Healthy Control subjects:&#xD;
&#xD;
               1. Absent doppler signal in brachial or radial arteries.&#xD;
&#xD;
               2. Asymmetric cyanosis, poor capillary refill or cold temperature&#xD;
&#xD;
               3. Known venous thrombosis or there is asymmetric swelling (arm circumference &gt; 2&#xD;
                  inches larger than opposite side).&#xD;
&#xD;
               4. Evidence of inflammation or impaired skin integrity of the involved limb.&#xD;
&#xD;
               5. History of surgery involving the blood or lymphatic vessels of this limb,&#xD;
                  including axillary lymph node dissection, will preclude this testing.&#xD;
&#xD;
               6. History of Anemia or G6PD deficiency&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anthony P. Pietropaoli, M.D., M.P.H.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Rochester</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Wexler O, Morgan MA, Gough MS, Steinmetz SD, Mack CM, Darling DC, Doolin KP, Apostolakos MJ, Graves BT, Frampton MW, Chen X, Pietropaoli AP. Brachial artery reactivity in patients with severe sepsis: an observational study. Crit Care. 2012 Dec 12;16(2):R38. doi: 10.1186/cc11223.</citation>
    <PMID>22390813</PMID>
  </reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>July 6, 2012</study_first_submitted>
  <study_first_submitted_qc>November 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <last_update_submitted>February 11, 2020</last_update_submitted>
  <last_update_submitted_qc>February 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Rochester</investigator_affiliation>
    <investigator_full_name>Anthony P. Pietropaoli</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>critical care</keyword>
  <keyword>severe sepsis</keyword>
  <keyword>microvascular function</keyword>
  <keyword>ultrasound</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Hyperemia</mesh_term>
    <mesh_term>Critical Illness</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/NCT01726595
org study id: 00030546
nct id: NCT01726595
lead sponsor: 
has dmc: No
The investigators hypothesize that doctors and nurses can undergo a brief period of training
      and then use ultrasound to accurately measure blood flow in a forearm artery after a brief
      period when this flow is interrupted with a blood pressure cuff, a measurement the
      investigators call reactive hyperemia. Reactive hyperemia indicates whether the small blood
      vessels in the body are healthy -- lower reactive hyperemia indicates worse small blood
      vessel function. When measured by experienced ultrasound experts, low reactive hyperemia
      strongly predicts death in critically ill patients with infection (severe sepsis).

      The investigators are conducting this study to determine if doctors and nurses, without
      specific pre-existing expertise in ultrasound, can be trained to make these measurements
      accurately. If so, the investigators will prove that these measurements can be applied
      reliably in real-world practice.

      The investigators also hypothesize that reactive hyperemia predict the outcomes of illness
      not just in patients with severe infection, but in other critically ill patients as well.

      Finally, the investigators hypothesize that reduced blood flow after blood pressure cuff
      occlusion is linked with other abnormalities of blood, previously identified in critically
      ill patients. For example, red blood cells from patients with severe sepsis have been shown
      to be stiffer than normal, so they are less able to flow along the small blood vessel
      passages of the body. Red blood cells become stiffer when there is a certain type of stress
      in the body known as "oxidative stress."

      If the investigators show that low reactive hyperemia, stiff red blood cells, and oxidative
      stress are linked, the investigators hope to develop new treatments that reduce oxidative
      stress, reduce the stiffness of red blood cells, and in turn improve reactive hyperemia.
      Improvements in reactive hyperemia indicate improvements in small blood vessel function.
      Better small blood vessel function means better delivery of oxygen throughout the body. The
      investigators believe that this will improve outcomes for critically ill patients.
observational model: Cohort
time perspective: Prospective
measure: hospital mortality
time frame: vital status at hospital discharge, an expected average of 3 weeks
arm group label: severe sepsis
description: Patients with severe sepsis or septic shock
arm group label: non-infected critically ill
description: Patients with severe non-infectious systemic inflammatory response syndrome
arm group label: healthy
description: healthy volunteers
Blood and urine specimens will be obtained within 48 hours of diagnosis of severe sepsis or
      severe non-infectious systemic inflammatory response syndrome. Subsequent blood and urine
      samples will be obtained 3-5 days after the first set of samples, within 48 hours of ICU
      discharge, and within 48 hours of hospital discharge. Samples will analyzed immediately or
      stored at -80 degrees celsius until use.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Anthony P. Pietropaoli, M.D., M.P.H.
role: Principal Investigator
affiliation: University of Rochester
facility: 
country: United States
citation: Wexler O, Morgan MA, Gough MS, Steinmetz SD, Mack CM, Darling DC, Doolin KP, Apostolakos MJ, Graves BT, Frampton MW, Chen X, Pietropaoli AP. Brachial artery reactivity in patients with severe sepsis: an observational study. Crit Care. 2012 Dec 12;16(2):R38. doi: 10.1186/cc11223.
PMID: 22390813
responsible party type: Principal Investigator
investigator affiliation: University of Rochester
investigator full name: Anthony P. Pietropaoli
investigator title: Professor of Medicine
mesh term: Sepsis
mesh term: Hyperemia
mesh term: Critical Illness