<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/NCT01669434</url>
  </required_header>
  <id_info>
    <org_study_id>369-12-FB</org_study_id>
    <nct_id>NCT01669434</nct_id>
  </id_info>
  <brief_title>Chronic Angiotensin Converting Enzyme Inhibitors in Intermediate Risk Surgery</brief_title>
  <official_title>Chronic Angiotensin Converting Enzyme Inhibitors in Intermediate Risk Surgery: A Randomized, Single-Blinded Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nebraska</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Nebraska</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary research hypothesis: Patients who continue their chronic ACEI therapy up to and&#xD;
      including the morning of a non-cardiac, non-vascular surgery will experience more&#xD;
      intraoperative hypotension than those who transiently hold their chronic ACEI preoperatively.&#xD;
&#xD;
      Secondary research hypothesis #1: Patients who continue their chronic ACEI up to and&#xD;
      including the morning of a non-cardiac, non-vascular surgery will experience better&#xD;
      postoperative control of hypertension than those who transiently hold their chronic ACEI&#xD;
      preoperatively.&#xD;
&#xD;
      Secondary research hypothesis #2: Patients who continue their chronic ACEI up to and&#xD;
      including the morning of a non-cardiac, non-vascular surgery will experience less acute renal&#xD;
      failure than those who transiently hold their chronic ACEI preoperatively.&#xD;
&#xD;
      Secondary research hypothesis #3: In the subgroup of patients with a preoperative systolic&#xD;
      blood pressure less than 110 mmHg, those who continue their chronic ACEI therapy up to and&#xD;
      including the morning of a non-cardiac, non-vascular surgery will experience more&#xD;
      intraoperative hypotension than those who transiently hold their chronic ACEI preoperatively.&#xD;
&#xD;
      Secondary research hypothesis #4: In the subgroup of patients above the age of 64, those who&#xD;
      continue their chronic ACEI therapy up to and including the morning of a non-cardiac,&#xD;
      non-vascular surgery will experience more intraoperative hypotension than those who&#xD;
      transiently hold their chronic ACEI preoperatively.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to determine if transient discontinuation of angiotensin&#xD;
      converting enzyme inhibitors (ACEIs) is necessary prior to non-cardiac, non-vascular surgery.&#xD;
      ACEIs have been associated with intraoperative hypotension during vascular and cardiac&#xD;
      surgeries. Patients presenting to the University of Nebraska Medical Center Pre-Anesthesia&#xD;
      Screening (PAS) Clinic who are on chronic ACEI therapy will be eligible for enrollment.&#xD;
      Subjects will be randomized to either omit or continue their ACEI preoperatively. The outcome&#xD;
      of interest is intraoperative hypotension defined as a systolic blood pressure less than 80&#xD;
      mmHg. Blood pressure will be followed not only throughout surgery, but also during recovery&#xD;
      and the remainder of hospitalization. Renal function will be assessed with creatinine&#xD;
      measurements in the PAS clinic and on the first postoperative day. No follow-up is planned&#xD;
      beyond discharge from the hospital.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2015</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">November 2016</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Interoperative Hypotension</measure>
    <time_frame>During anesthesia, an expected average of 3 hours.</time_frame>
    <description>Systolic Blood Pressure under 80 mmHg</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acute Renal Failure</measure>
    <time_frame>Arrival in post-anesthesia care unit (PACU) to hospital discharge, an expected average of 4 days.</time_frame>
    <description>Creatinine increase of more than 0.3 mg/dl or more than 50% from preoperative level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Low Blood Pressure Subgroup</measure>
    <time_frame>During anesthesia, an expected average of 3 hours.</time_frame>
    <description>Only patients with systolic blood pressure less than 110 at preoperative evaluation will be included in this analysis. The outcome is the same as the primary outcome: Intraoperative Systolic Blood Pressure under 80 mmHg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Older Age Subgroup</measure>
    <time_frame>During anesthesia, an expected average of 3 hours.</time_frame>
    <description>Only patients above the age of 64 will be included in this analysis. The outcome is the same as the primary outcome: Intraoperative Systolic Blood Pressure under 80 mmHg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative Hypertension</measure>
    <time_frame>Arrival in PACU to hospital discharge, an expected average of 4 days.</time_frame>
    <description>Any systolic blood pressure greater than 180 mmHg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative Hypotension</measure>
    <time_frame>Arrival in PACU to hospital discharge, an expected average of 4 days.</time_frame>
    <description>Any systolic blood pressure less than 90 mmHg</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">291</enrollment>
  <condition>Hypotension on Induction</condition>
  <arm_group>
    <arm_group_label>ACEI continuation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in this arm will be randomized to continue their chronic angiotensin converting enzyme inhibitor without interruption preoperatively</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ACEI omission</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to this arm will be told to omit their final preoperative chronic angiotensin converting enzyme inhibitor dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ACEI continuation</intervention_name>
    <description>These chronic medications will be taken without interruption preoperatively.</description>
    <arm_group_label>ACEI continuation</arm_group_label>
    <other_name>quinapril</other_name>
    <other_name>Accupril</other_name>
    <other_name>perindopril</other_name>
    <other_name>Aceon</other_name>
    <other_name>ramipril</other_name>
    <other_name>Altace</other_name>
    <other_name>benazepril</other_name>
    <other_name>Lotensin</other_name>
    <other_name>captopril</other_name>
    <other_name>Capoten</other_name>
    <other_name>enalapril</other_name>
    <other_name>Vasotec</other_name>
    <other_name>fosinopril</other_name>
    <other_name>Monopril</other_name>
    <other_name>lisinopril</other_name>
    <other_name>Prinivil</other_name>
    <other_name>Zestril</other_name>
    <other_name>trandolapril</other_name>
    <other_name>Mavik</other_name>
    <other_name>moexipril</other_name>
    <other_name>Univasc</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ACEI omission</intervention_name>
    <description>Although taken chronically by patients in this intervention, the final preoperative dose of these medications will be omitted, whether it was scheduled for the morning of surgery or the day prior.</description>
    <arm_group_label>ACEI omission</arm_group_label>
    <other_name>quinapril</other_name>
    <other_name>Accupril</other_name>
    <other_name>perindopril</other_name>
    <other_name>Aceon</other_name>
    <other_name>ramipril</other_name>
    <other_name>Altace</other_name>
    <other_name>benazepril</other_name>
    <other_name>Lotensin</other_name>
    <other_name>captopril</other_name>
    <other_name>Capoten</other_name>
    <other_name>enalapril</other_name>
    <other_name>Vasotec</other_name>
    <other_name>fosinopril</other_name>
    <other_name>Monopril</other_name>
    <other_name>lisinopril</other_name>
    <other_name>Prinivil</other_name>
    <other_name>Zestril</other_name>
    <other_name>trandolapril</other_name>
    <other_name>Mavik</other_name>
    <other_name>moexipril</other_name>
    <other_name>Univasc</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Referred to the University of Nebraska Medical Center Pre-Anesthesia Screening Clinic&#xD;
             for preoperative evaluation.&#xD;
&#xD;
          -  Above referral must be in anticipation of a non-cardiac, non-vascular surgery.&#xD;
&#xD;
          -  Must have been on ACE-Inhibitor therapy for at least six weeks.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hypotension (systolic blood pressure &lt; 90 or diastolic blood pressure &lt;60) at the time&#xD;
             of preoperative evaluation&#xD;
&#xD;
          -  Uncontrolled Hypertension (systolic blood pressure &gt; 150 or diastolic blood pressure &gt;&#xD;
             95) at the time of preoperative evaluation&#xD;
&#xD;
          -  Surgery during which vasopressor use is anticipated (carotid endarterectomy, major&#xD;
             abdominal operations, orthopedic oncology)&#xD;
&#xD;
          -  Surgery for pathology related to vasoactive substances (carcinoid, pheochromocytoma)&#xD;
&#xD;
          -  Left Ventricular ejection fraction less than 40%&#xD;
&#xD;
          -  Clinical evidence of decompensated heart failure at the time of preoperative&#xD;
             evaluation&#xD;
&#xD;
          -  End-stage renal disease&#xD;
&#xD;
          -  Organ transplant surgeries&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jason F Shiffermiller, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Nebraska</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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    <PMID>2692007</PMID>
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    <PMID>27775997</PMID>
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    <citation>Drenger B, Fontes ML, Miao Y, Mathew JP, Gozal Y, Aronson S, Dietzel C, Mangano DT; Investigators of the Ischemia Research and Education Foundation; Multicenter Study of Perioperative Ischemia Research Group. Patterns of use of perioperative angiotensin-converting enzyme inhibitors in coronary artery bypass graft surgery with cardiopulmonary bypass: effects on in-hospital morbidity and mortality. Circulation. 2012 Jul 17;126(3):261-9. doi: 10.1161/CIRCULATIONAHA.111.059527. Epub 2012 Jun 19.</citation>
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  <verification_date>November 2017</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2012</study_first_posted>
  <results_first_submitted>October 9, 2017</results_first_submitted>
  <results_first_submitted_qc>November 8, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 11, 2017</results_first_posted>
  <last_update_submitted>November 8, 2017</last_update_submitted>
  <last_update_submitted_qc>November 8, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Nebraska</investigator_affiliation>
    <investigator_full_name>Jason Shiffermiller, MD</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Perioperative Period</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypotension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ramipril</mesh_term>
    <mesh_term>Enalapril</mesh_term>
    <mesh_term>Enalaprilat</mesh_term>
    <mesh_term>Lisinopril</mesh_term>
    <mesh_term>Perindopril</mesh_term>
    <mesh_term>Benazepril</mesh_term>
    <mesh_term>Captopril</mesh_term>
    <mesh_term>Quinapril</mesh_term>
    <mesh_term>Trandolapril</mesh_term>
    <mesh_term>Fosinopril</mesh_term>
    <mesh_term>Moexipril</mesh_term>
    <mesh_term>Angiotensin-Converting Enzyme Inhibitors</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>ACEI Omission</title>
          <description>Patients randomized to this arm will be told to hold their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI omission: These medications, although taken chronically by patients in this intervention, will not be given on the morning of surgery or day before surgery, whenever the last preoperative dose would normally occur.</description>
        </group>
        <group group_id="P2">
          <title>ACEI Continuation</title>
          <description>Patients in this arm will be randomized to take their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI continuation: These chronic medications will be given without interruption preoperatively.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="146"/>
                <participants group_id="P2" count="145"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="137"/>
                <participants group_id="P2" count="138"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>ACEI Omission</title>
          <description>Patients randomized to this arm will be told to hold their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI omission: These medications, although taken chronically by patients in this intervention, will not be given on the morning of surgery or evening before surgery, whenever the last preoperative dose would normally occur.</description>
        </group>
        <group group_id="B2">
          <title>ACEI Continuation</title>
          <description>Patients in this arm will be randomized to take their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI continuation: These chronic medications will be given without interruption preoperatively.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="137"/>
            <count group_id="B2" value="138"/>
            <count group_id="B3" value="275"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64" lower_limit="26" upper_limit="91"/>
                    <measurement group_id="B2" value="63.7" lower_limit="31" upper_limit="86"/>
                    <measurement group_id="B3" value="63.9" lower_limit="26" upper_limit="91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="72"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="142"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="65"/>
                    <measurement group_id="B2" value="68"/>
                    <measurement group_id="B3" value="133"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Caucasian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="115"/>
                    <measurement group_id="B2" value="125"/>
                    <measurement group_id="B3" value="240"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Am Indian/Alaska</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other/Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="137"/>
                    <measurement group_id="B2" value="138"/>
                    <measurement group_id="B3" value="275"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>smoking status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Never</title>
                  <measurement_list>
                    <measurement group_id="B1" value="63"/>
                    <measurement group_id="B2" value="54"/>
                    <measurement group_id="B3" value="117"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Former</title>
                  <measurement_list>
                    <measurement group_id="B1" value="60"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="119"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Current</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>American Society of Anesthesiologists classification</title>
          <description>Scale range 1-6 I A normal healthy patient Healthy, non-smoking, no or minimal alcohol use 2 A patient with mild systemic disease 3 A patient with severe systemic disease 4 A patient with severe systemic disease that is a constant threat to life 5 A moribund patient who is not expected to survive without the operation 6 A declared brain-dead patient whose organs are being removed for donor purposes</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.8" lower_limit="1" upper_limit="4"/>
                    <measurement group_id="B2" value="2.8" lower_limit="2" upper_limit="4"/>
                    <measurement group_id="B3" value="2.8" lower_limit="1" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>preoperative NSAID use</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                    <measurement group_id="B2" value="71"/>
                    <measurement group_id="B3" value="124"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>preoperative systolic BP</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="136.6" lower_limit="99" upper_limit="187"/>
                    <measurement group_id="B2" value="136.3" lower_limit="102" upper_limit="184"/>
                    <measurement group_id="B3" value="136.5" lower_limit="99" upper_limit="187"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>hypertension history</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="116"/>
                    <measurement group_id="B2" value="112"/>
                    <measurement group_id="B3" value="228"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>congestive heart failure history</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Additional antihypertensive</title>
          <description>Use of at least one additional antihypertensive medication in addition to an angiotensin converting enzyme inhibitor at the time of enrollment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="92"/>
                    <measurement group_id="B2" value="95"/>
                    <measurement group_id="B3" value="187"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Interoperative Hypotension</title>
        <description>Systolic Blood Pressure under 80 mmHg</description>
        <time_frame>During anesthesia, an expected average of 3 hours.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ACEI Omission</title>
            <description>Patients randomized to this arm will be told to hold their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI omission: These medications, although taken chronically by patients in this intervention, will not be given on the morning of surgery or evening before surgery, whenever the last preoperative dose would normally occur.</description>
          </group>
          <group group_id="O2">
            <title>ACEI Continuation</title>
            <description>Patients in this arm will be randomized to take their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI continuation: These chronic medications will be given without interruption preoperatively.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Interoperative Hypotension</title>
          <description>Systolic Blood Pressure under 80 mmHg</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="137"/>
                <count group_id="O2" value="138"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76"/>
                    <measurement group_id="O2" value="95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.03</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>0.81</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.67</ci_lower_limit>
            <ci_upper_limit>0.97</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Acute Renal Failure</title>
        <description>Creatinine increase of more than 0.3 mg/dl or more than 50% from preoperative level</description>
        <time_frame>Arrival in post-anesthesia care unit (PACU) to hospital discharge, an expected average of 4 days.</time_frame>
        <population>Missing outcome data for 37 patients, 18 in the ACEI omission arm and 19 in the ACEI continuation arm</population>
        <group_list>
          <group group_id="O1">
            <title>ACEI Omission</title>
            <description>Patients randomized to this arm will be told to hold their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI omission: These medications, although taken chronically by patients in this intervention, will not be given on the morning of surgery or evening before surgery, whenever the last preoperative dose would normally occur.</description>
          </group>
          <group group_id="O2">
            <title>ACEI Continuation</title>
            <description>Patients in this arm will be randomized to take their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI continuation: These chronic medications will be given without interruption preoperatively.</description>
          </group>
        </group_list>
        <measure>
          <title>Acute Renal Failure</title>
          <description>Creatinine increase of more than 0.3 mg/dl or more than 50% from preoperative level</description>
          <population>Missing outcome data for 37 patients, 18 in the ACEI omission arm and 19 in the ACEI continuation arm</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="119"/>
                <count group_id="O2" value="119"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.44</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>0.60</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.23</ci_lower_limit>
            <ci_upper_limit>1.60</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Low Blood Pressure Subgroup</title>
        <description>Only patients with systolic blood pressure less than 110 at preoperative evaluation will be included in this analysis. The outcome is the same as the primary outcome: Intraoperative Systolic Blood Pressure under 80 mmHg.</description>
        <time_frame>During anesthesia, an expected average of 3 hours.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ACEI Omission</title>
            <description>Patients randomized to this arm will be told to hold their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI omission: These medications, although taken chronically by patients in this intervention, will not be given on the morning of surgery or evening before surgery, whenever the last preoperative dose would normally occur.</description>
          </group>
          <group group_id="O2">
            <title>ACEI Continuation</title>
            <description>Patients in this arm will be randomized to take their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI continuation: These chronic medications will be given without interruption preoperatively.</description>
          </group>
        </group_list>
        <measure>
          <title>Low Blood Pressure Subgroup</title>
          <description>Only patients with systolic blood pressure less than 110 at preoperative evaluation will be included in this analysis. The outcome is the same as the primary outcome: Intraoperative Systolic Blood Pressure under 80 mmHg.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.0</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>1.20</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.48</ci_lower_limit>
            <ci_upper_limit>2.99</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Older Age Subgroup</title>
        <description>Only patients above the age of 64 will be included in this analysis. The outcome is the same as the primary outcome: Intraoperative Systolic Blood Pressure under 80 mmHg</description>
        <time_frame>During anesthesia, an expected average of 3 hours.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ACEI Omission</title>
            <description>Patients randomized to this arm will be told to hold their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI omission: These medications, although taken chronically by patients in this intervention, will not be given on the morning of surgery or evening before surgery, whenever the last preoperative dose would normally occur.</description>
          </group>
          <group group_id="O2">
            <title>ACEI Continuation</title>
            <description>Patients in this arm will be randomized to take their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI continuation: These chronic medications will be given without interruption preoperatively.</description>
          </group>
        </group_list>
        <measure>
          <title>Older Age Subgroup</title>
          <description>Only patients above the age of 64 will be included in this analysis. The outcome is the same as the primary outcome: Intraoperative Systolic Blood Pressure under 80 mmHg</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="72"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48"/>
                    <measurement group_id="O2" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.0</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>1.01</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.81</ci_lower_limit>
            <ci_upper_limit>1.26</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Postoperative Hypertension</title>
        <description>Any systolic blood pressure greater than 180 mmHg.</description>
        <time_frame>Arrival in PACU to hospital discharge, an expected average of 4 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ACEI Omission</title>
            <description>Patients randomized to this arm will be told to hold their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI omission: These medications, although taken chronically by patients in this intervention, will not be given on the morning of surgery or evening before surgery, whenever the last preoperative dose would normally occur.</description>
          </group>
          <group group_id="O2">
            <title>ACEI Continuation</title>
            <description>Patients in this arm will be randomized to take their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI continuation: These chronic medications will be given without interruption preoperatively.</description>
          </group>
        </group_list>
        <measure>
          <title>Postoperative Hypertension</title>
          <description>Any systolic blood pressure greater than 180 mmHg.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="137"/>
                <count group_id="O2" value="138"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.01</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>1.95</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.14</ci_lower_limit>
            <ci_upper_limit>3.34</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Postoperative Hypotension</title>
        <description>Any systolic blood pressure less than 90 mmHg</description>
        <time_frame>Arrival in PACU to hospital discharge, an expected average of 4 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ACEI Omission</title>
            <description>Patients randomized to this arm will be told to hold their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI omission: These medications, although taken chronically by patients in this intervention, will not be given on the morning of surgery or evening before surgery, whenever the last preoperative dose would normally occur.</description>
          </group>
          <group group_id="O2">
            <title>ACEI Continuation</title>
            <description>Patients in this arm will be randomized to take their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI continuation: These chronic medications will be given without interruption preoperatively.</description>
          </group>
        </group_list>
        <measure>
          <title>Postoperative Hypotension</title>
          <description>Any systolic blood pressure less than 90 mmHg</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="137"/>
                <count group_id="O2" value="138"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.02</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>0.49</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.28</ci_lower_limit>
            <ci_upper_limit>0.86</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Hospitalization, expected duration 4 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>ACEI Omission</title>
          <description>Patients randomized to this arm will be told to hold their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI omission: These medications, although taken chronically by patients in this intervention, will not be given on the morning of surgery or evening before surgery, whenever the last preoperative dose would normally occur.</description>
        </group>
        <group group_id="E2">
          <title>ACEI Continuation</title>
          <description>Patients in this arm will be randomized to take their final preoperative angiotensin converting enzyme inhibitor dose.&#xD;
ACEI continuation: These chronic medications will be given without interruption preoperatively.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="137"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="138"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="137"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="138"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>MACE</sub_title>
                <description>Major Adverse Cardiac Event. A composite of acute coronary syndrome, acute heart failure, or new-onset arrhythmia</description>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="137"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="138"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="137"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="138"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Management decisions were made by the treatment which was not blinded to allocation; Intraoperative hypotension is an intermediate measure but one that has known associations with adverse outcomes, including mortality.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Jason Shiffermiller</name_or_title>
      <organization>University of Nebraska Medical Center</organization>
      <phone>402-559-7299</phone>
      <email>jshiffermiller@unmc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01669434
org study id: 369-12-FB
nct id: NCT01669434
lead sponsor: 
has dmc: Yes
Primary research hypothesis: Patients who continue their chronic ACEI therapy up to and
      including the morning of a non-cardiac, non-vascular surgery will experience more
      intraoperative hypotension than those who transiently hold their chronic ACEI preoperatively.

      Secondary research hypothesis #1: Patients who continue their chronic ACEI up to and
      including the morning of a non-cardiac, non-vascular surgery will experience better
      postoperative control of hypertension than those who transiently hold their chronic ACEI
      preoperatively.

      Secondary research hypothesis #2: Patients who continue their chronic ACEI up to and
      including the morning of a non-cardiac, non-vascular surgery will experience less acute renal
      failure than those who transiently hold their chronic ACEI preoperatively.

      Secondary research hypothesis #3: In the subgroup of patients with a preoperative systolic
      blood pressure less than 110 mmHg, those who continue their chronic ACEI therapy up to and
      including the morning of a non-cardiac, non-vascular surgery will experience more
      intraoperative hypotension than those who transiently hold their chronic ACEI preoperatively.

      Secondary research hypothesis #4: In the subgroup of patients above the age of 64, those who
      continue their chronic ACEI therapy up to and including the morning of a non-cardiac,
      non-vascular surgery will experience more intraoperative hypotension than those who
      transiently hold their chronic ACEI preoperatively.
The purpose of this study is to determine if transient discontinuation of angiotensin
      converting enzyme inhibitors (ACEIs) is necessary prior to non-cardiac, non-vascular surgery.
      ACEIs have been associated with intraoperative hypotension during vascular and cardiac
      surgeries. Patients presenting to the University of Nebraska Medical Center Pre-Anesthesia
      Screening (PAS) Clinic who are on chronic ACEI therapy will be eligible for enrollment.
      Subjects will be randomized to either omit or continue their ACEI preoperatively. The outcome
      of interest is intraoperative hypotension defined as a systolic blood pressure less than 80
      mmHg. Blood pressure will be followed not only throughout surgery, but also during recovery
      and the remainder of hospitalization. Renal function will be assessed with creatinine
      measurements in the PAS clinic and on the first postoperative day. No follow-up is planned
      beyond discharge from the hospital.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Interoperative Hypotension
time frame: During anesthesia, an expected average of 3 hours.
description: Systolic Blood Pressure under 80 mmHg
measure: Acute Renal Failure
time frame: Arrival in post-anesthesia care unit (PACU) to hospital discharge, an expected average of 4 days.
description: Creatinine increase of more than 0.3 mg/dl or more than 50% from preoperative level
measure: Low Blood Pressure Subgroup
time frame: During anesthesia, an expected average of 3 hours.
description: Only patients with systolic blood pressure less than 110 at preoperative evaluation will be included in this analysis. The outcome is the same as the primary outcome: Intraoperative Systolic Blood Pressure under 80 mmHg.
measure: Older Age Subgroup
time frame: During anesthesia, an expected average of 3 hours.
description: Only patients above the age of 64 will be included in this analysis. The outcome is the same as the primary outcome: Intraoperative Systolic Blood Pressure under 80 mmHg
measure: Postoperative Hypertension
time frame: Arrival in PACU to hospital discharge, an expected average of 4 days.
description: Any systolic blood pressure greater than 180 mmHg.
measure: Postoperative Hypotension
time frame: Arrival in PACU to hospital discharge, an expected average of 4 days.
description: Any systolic blood pressure less than 90 mmHg
arm group label: ACEI continuation
arm group type: Experimental
description: Patients in this arm will be randomized to continue their chronic angiotensin converting enzyme inhibitor without interruption preoperatively
arm group label: ACEI omission
arm group type: Experimental
description: Patients randomized to this arm will be told to omit their final preoperative chronic angiotensin converting enzyme inhibitor dose.
intervention type: Drug
intervention name: ACEI continuation
description: These chronic medications will be taken without interruption preoperatively.
arm group label: ACEI continuation
other name: quinapril
other name: Accupril
other name: perindopril
other name: Aceon
other name: ramipril
other name: Altace
other name: benazepril
other name: Lotensin
other name: captopril
other name: Capoten
other name: enalapril
other name: Vasotec
other name: fosinopril
other name: Monopril
other name: lisinopril
other name: Prinivil
other name: Zestril
other name: trandolapril
other name: Mavik
other name: moexipril
other name: Univasc
intervention type: Drug
intervention name: ACEI omission
description: Although taken chronically by patients in this intervention, the final preoperative dose of these medications will be omitted, whether it was scheduled for the morning of surgery or the day prior.
arm group label: ACEI omission
other name: quinapril
other name: Accupril
other name: perindopril
other name: Aceon
other name: ramipril
other name: Altace
other name: benazepril
other name: Lotensin
other name: captopril
other name: Capoten
other name: enalapril
other name: Vasotec
other name: fosinopril
other name: Monopril
other name: lisinopril
other name: Prinivil
other name: Zestril
other name: trandolapril
other name: Mavik
other name: moexipril
other name: Univasc
criteria: 
gender: All
minimum age: 19 Years
maximum age: 90 Years
healthy volunteers: No
last name: Jason F Shiffermiller, MD, MPH
role: Principal Investigator
affiliation: University of Nebraska
facility: 
country: United States
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responsible party type: Principal Investigator
investigator affiliation: University of Nebraska
investigator full name: Jason Shiffermiller, MD
investigator title: Assistant Professor
mesh term: Hypotension
mesh term: Ramipril
mesh term: Enalapril
mesh term: Enalaprilat
mesh term: Lisinopril
mesh term: Perindopril
mesh term: Benazepril
mesh term: Captopril
mesh term: Quinapril
mesh term: Trandolapril
mesh term: Fosinopril
mesh term: Moexipril
mesh term: Angiotensin-Converting Enzyme Inhibitors
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Management decisions were made by the treatment which was not blinded to allocation; Intraoperative hypotension is an intermediate measure but one that has known associations with adverse outcomes, including mortality.
point of contact: 