<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/NCT01709227</url>
  </required_header>
  <id_info>
    <org_study_id>2011-1730</org_study_id>
    <nct_id>NCT01709227</nct_id>
  </id_info>
  <brief_title>Peritoneal Dialysis vs Furosemide for Acute Kidney Injury After Cardiopulmonary Bypass</brief_title>
  <official_title>Early Renal Replacement Therapy vs. Furosemide for Neonates With Oliguria After Cardiopulmonary Bypass</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital Medical Center, Cincinnati</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acute kidney injury (AKI) after cardiopulmonary bypass (CPB) in infants is common and&#xD;
      associated with poor outcomes. Peritoneal dialysis (PD) and furosemide have been used to&#xD;
      attain negative fluid balance due to AKI induced oliguria, but have not been compared&#xD;
      prospectively. The investigators will prospectively compare outcomes of infants with oliguria&#xD;
      after CPB randomized to PD vs. furosemide with the hypothesis that infants receiving PD have&#xD;
      superior outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Acute kidney injury (AKI) is a common postoperative complication after heart&#xD;
      surgery with cardiopulmonary bypass (CPB). Multiple studies have demonstrated that patients&#xD;
      with AKI have worse clinical outcomes, such as longer ventilation times and increased length&#xD;
      of stay, which is thought to be secondary to associated oliguria and subsequent fluid&#xD;
      overload. Studies suggest that early renal replacement therapy (RRT) via peritoneal dialysis&#xD;
      (PD) may prevent fluid overload and therefore be a superior management to diuretic (i.e.&#xD;
      furosemide) administration. However, there is no published evidence to suggest superiority or&#xD;
      laboratory data available to guide decision making.&#xD;
&#xD;
      Objective: Our primary objective is to determine if early institution of PD improves clinical&#xD;
      outcomes compared to administration of furosemide in post-operative cardiac infants with&#xD;
      acute kidney injury. We hypothesize that early initiation of PD will improve clinical&#xD;
      outcomes. We will determine if these clinical outcomes will be better among good responders&#xD;
      of furosemide compared to poor responders. We will determine if postoperative NGAL&#xD;
      concentrations are predictive of poor response to furosemide.&#xD;
&#xD;
      Design / Methods: The study will be a single-center randomized clinical trial among neonates&#xD;
      undergoing cardiac surgery with CPB with planned placement of a PD catheter due to risk of&#xD;
      AKI. If patients demonstrate oliguria within the first postoperative day, they will be&#xD;
      randomized to early PD or trial of furosemide. Clinical and laboratory data will be collected&#xD;
      and compared between groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2011</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Negative Fluid Balance on Postop Day 1</measure>
    <time_frame>Postop day 1</time_frame>
    <description>Difference of inputs and outputs, including urine output and PD drainage.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Respiratory Support Administered</measure>
    <time_frame>Duration of postoperative intubation (average time approximately- 1 week)</time_frame>
    <description>Duration of initial course of postoperative mechanical ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NGAL Concentration</measure>
    <time_frame>Pre-op, and postop (2hr, 6hr, 12hr, 24hr, 48hr)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Cardiac ICU Stay</measure>
    <time_frame>Average 2 weeks</time_frame>
    <description>Total days of initial postoperative stay in cardiac ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Hospital Stay</measure>
    <time_frame>Average 4 weeks</time_frame>
    <description>Total days of initial postoperative stay in hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All Cause Mortality</measure>
    <time_frame>duration of hospitalization (an average of 2 weeks)</time_frame>
    <description>In-hospital mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal/Electrolyte Abnormalities</measure>
    <time_frame>Postop morning 1-5</time_frame>
    <description>Total sum of renal and electrolyte abnormalities over the first 5 postoperative days as defined in the protocol</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Doses of Potassium Chloride or Arginine Chloride Required</measure>
    <time_frame>Postop day 0-5</time_frame>
    <description>Total doses of potassium chloride or arginine chloride given during the first five postoperative days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>B-Natriuretic Peptide</measure>
    <time_frame>At 24hours and 48 hours postoperative</time_frame>
    <description>BNP measured at 24 and 48 hours postoperatively</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Oxygenation Index</measure>
    <time_frame>at 24 and 48 hours postoperative</time_frame>
    <description>Product of Mean airway pressure delivered by mechanical ventilation and FiO2 of administered oxygen</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">73</enrollment>
  <condition>Acute Kidney Injury</condition>
  <arm_group>
    <arm_group_label>Furosemide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to the furosemide arm will be given 1 mg/kg intravenously every 6 hours for 2 doses and then as directed by CICU attending to augment urine output. Patients within this arm who have urine output &lt;1 ml/kg/hr over 16 hours after the first dose of Lasix will be considered poor responders. These patients may be started on PD if clinically indicated. Those who show good response (urine output &gt;1 ml/kg/hr over subsequent 16 hours) will continue furosemide as needed to augment urine output. If they subsequently develop oliguria or fluid overload unresponsive to diuretic therapy, these patients may later be started on PD at discretion of CICU attending with consultation of nephrology service.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Peritoneal dialysis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients within the PD arm will begin PD with a standardized dialysis plan of 10ml/kg of 1.5% Dianeal™ with 1 hours cycles (5 minute fill, 45 minute dwell and 10 minute drain). Further PD management will be directed by CICU attending and Nephrology service</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Furosemide</intervention_name>
    <description>Patients randomized to the furosemide arm will be given 1 mg/kg intravenously every 6 hours for 2 doses and then as directed by CICU attending to augment urine output. Patients within this arm who have urine output &lt;1 ml/kg/hr over 16 hours after the first dose of Lasix will be considered poor responders. These patients may be started on PD if clinically indicated. Those who show good response (urine output &gt;1 ml/kg/hr over subsequent 16 hours) will continue furosemide as needed to augment urine output. If they subsequently develop oliguria or fluid overload unresponsive to diuretic therapy, these patients may later be started on PD at discretion of CICU attending with consultation of nephrology service.</description>
    <arm_group_label>Furosemide</arm_group_label>
    <other_name>Lasix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Peritoneal Dialysis</intervention_name>
    <description>Patients within the PD arm will begin PD with a standardized dialysis plan of 10ml/kg of 1.5% Dianeal™ with 1 hours cycles (5 minute fill, 45 minute dwell and 10 minute drain). Further PD management and discontinuation will be directed by CICU attending and Nephrology service.</description>
    <arm_group_label>Peritoneal dialysis</arm_group_label>
    <other_name>PD</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age less than 6 months of age;&#xD;
&#xD;
          -  Undergoing cardiothoracic surgery with CPB;&#xD;
&#xD;
          -  Planned placement of PD catheter per institutional standard of care criteria.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pre-existing chronic kidney disease stage 3 or above (correlating with estimated&#xD;
             GFR&lt;60 ml/min/m2, which will be calculated using routine preoperative serum creatinine&#xD;
             value using the modified Schwartz equation).&#xD;
&#xD;
          -  Known history of allergy to furosemide.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>6 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David M Kwiatkowski, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cinncinnati Children's Hospital Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Catherine D Krawczeski, MD</last_name>
    <role>Study Director</role>
    <affiliation>Cinncinnati Children's Hospital Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stuart L Goldstein, MD</last_name>
    <role>Study Director</role>
    <affiliation>Cinncinnati Children's Hospital Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cincinnati Childrens Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45223</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.cincinnatichildrens.org/service/c/cacn/default/</url>
    <description>Center for Acute Care Nephology at Cincinnati Childrens</description>
  </link>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>September 20, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <results_first_submitted>January 31, 2017</results_first_submitted>
  <results_first_submitted_qc>May 4, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">June 9, 2017</results_first_posted>
  <last_update_submitted>May 4, 2017</last_update_submitted>
  <last_update_submitted_qc>May 4, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acute kidney injury</keyword>
  <keyword>AKI</keyword>
  <keyword>cardiopulmonary bypass</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Kidney Injury</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Furosemide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified patient data would be available to other researchers after publication of data at the discretion of the research team after communication with the PI</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Furosemide</title>
          <description>Patients randomized to the furosemide arm will be given 1 mg/kg intravenously every 6 hours for 2 doses and then as directed by CICU attending to augment urine output. Patients within this arm who have urine output &lt;1 ml/kg/hr over 16 hours after the first dose of Lasix will be considered poor responders. These patients may be started on PD if clinically indicated. Those who show good response (urine output &gt;1 ml/kg/hr over subsequent 16 hours) will continue furosemide as needed to augment urine output. If they subsequently develop oliguria or fluid overload unresponsive to diuretic therapy, these patients may later be started on PD at discretion of CICU attending with consultation of nephrology service.&#xD;
Furosemide: Patients randomized to the furosemide arm are given 1 mg/kg intravenously every 6 hours for 2 doses and then as directed by CICU attending to augment urine output. Patients within this arm who have urine output &lt;1 ml/kg/hr over 16 hours after the first dose of Lasix</description>
        </group>
        <group group_id="P2">
          <title>Peritoneal Dialysis</title>
          <description>Patients within the PD arm will begin PD with a standardized dialysis plan of 10ml/kg of 1.5% Dianeal™ with 1 hours cycles (5 minute fill, 45 minute dwell and 10 minute drain). Further PD management will be directed by CICU attending and Nephrology service&#xD;
Peritoneal Dialysis: Patients within the PD arm will begin PD with a standardized dialysis plan of 10ml/kg of 1.5% Dianeal™ with 1 hours cycles (5 minute fill, 45 minute dwell and 10 minute drain). Further PD management and discontinuation will be directed by CICU attending and Nephrology service.&#xD;
One potential outcome during use of a peritoneal dialysis catheter is the development of a Pleural Peritoneal communication. In this event, dialysis fluid is instilled in the peritoneum and then leaks into the pleural space through a defect in the diaphragm. This fluid is then drained out of a surgical chest tube. This impairs the ability to perform peritoneal dialysis and thus is a reason to not complete the randomized arm.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
                <participants group_id="P2" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pleural Peritoneal communication</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Furosemide</title>
          <description>Patients randomized to receive furosemide</description>
        </group>
        <group group_id="B2">
          <title>Peritoneal Dialysis</title>
          <description>Patients randomized to receive peritoneal dialysis</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="32"/>
            <count group_id="B2" value="41"/>
            <count group_id="B3" value="73"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9" lower_limit="7" upper_limit="14"/>
                    <measurement group_id="B2" value="8" lower_limit="6" upper_limit="15"/>
                    <measurement group_id="B3" value="8" lower_limit="6" upper_limit="14"/>
                  </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="11"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="71"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="66"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </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="32"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight (kg)</title>
          <units>kg</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.4" lower_limit="3" upper_limit="3.8"/>
                    <measurement group_id="B2" value="3.4" lower_limit="3" upper_limit="3.8"/>
                    <measurement group_id="B3" value="3.4" lower_limit="3" upper_limit="3.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Length (cm)</title>
          <units>cm</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50" lower_limit="47" upper_limit="53"/>
                    <measurement group_id="B2" value="50" lower_limit="47" upper_limit="52"/>
                    <measurement group_id="B3" value="50" lower_limit="47" upper_limit="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Creatinine (mg/dL)</title>
          <units>mg/dl</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.4" lower_limit="0.36" upper_limit="0.5"/>
                    <measurement group_id="B2" value="0.4" lower_limit="0.34" upper_limit="0.53"/>
                    <measurement group_id="B3" value="0.4" lower_limit="0.34" upper_limit="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Negative Fluid Balance on Postop Day 1</title>
        <description>Difference of inputs and outputs, including urine output and PD drainage.</description>
        <time_frame>Postop day 1</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Furosemide</title>
            <description>Patients randomized to furosemide</description>
          </group>
          <group group_id="O2">
            <title>Peritoneal Dialysis</title>
            <description>Patients randomized to peritoneal dialysis</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Negative Fluid Balance on Postop Day 1</title>
          <description>Difference of inputs and outputs, including urine output and PD drainage.</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="32"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Respiratory Support Administered</title>
        <description>Duration of initial course of postoperative mechanical ventilation</description>
        <time_frame>Duration of postoperative intubation (average time approximately- 1 week)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Furosemide</title>
            <description>Patients randomized to furosemide</description>
          </group>
          <group group_id="O2">
            <title>Peritoneal Dialysis</title>
            <description>Patients randomized to peritoneal dialysis</description>
          </group>
        </group_list>
        <measure>
          <title>Respiratory Support Administered</title>
          <description>Duration of initial course of postoperative mechanical ventilation</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="2" upper_limit="6"/>
                    <measurement group_id="O2" value="3" lower_limit="2" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>NGAL Concentration</title>
        <time_frame>Pre-op, and postop (2hr, 6hr, 12hr, 24hr, 48hr)</time_frame>
        <population>Data were collected but not analyzed. Due to a high incidence of volatile and un-reportable NGAL levels, concerns were raised about the storage or processing of samples affecting data validity. Given the overwhelming concern of erroneous data, analysis was not performed as planned.</population>
        <group_list>
          <group group_id="O1">
            <title>Furosemide</title>
            <description>Patients randomized to furosemide</description>
          </group>
          <group group_id="O2">
            <title>Peritoneal Dialysis</title>
            <description>Patients randomized to PD</description>
          </group>
        </group_list>
        <measure>
          <title>NGAL Concentration</title>
          <population>Data were collected but not analyzed. Due to a high incidence of volatile and un-reportable NGAL levels, concerns were raised about the storage or processing of samples affecting data validity. Given the overwhelming concern of erroneous data, analysis was not performed as planned.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Cardiac ICU Stay</title>
        <description>Total days of initial postoperative stay in cardiac ICU</description>
        <time_frame>Average 2 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Furosemide</title>
            <description>Patients randomized to furosemide</description>
          </group>
          <group group_id="O2">
            <title>Peritoneal Dialysis</title>
            <description>Patients randomized to peritoneal dialysis</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Cardiac ICU Stay</title>
          <description>Total days of initial postoperative stay in cardiac ICU</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9" lower_limit="5" upper_limit="15"/>
                    <measurement group_id="O2" value="7" lower_limit="6" upper_limit="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Hospital Stay</title>
        <description>Total days of initial postoperative stay in hospital</description>
        <time_frame>Average 4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Furosemide</title>
            <description>Patients randomized to furosemide</description>
          </group>
          <group group_id="O2">
            <title>Peritoneal Dialysis</title>
            <description>Patients randomized to peritoneal dialysis</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Hospital Stay</title>
          <description>Total days of initial postoperative stay in hospital</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15" lower_limit="10" upper_limit="28"/>
                    <measurement group_id="O2" value="14" lower_limit="9" upper_limit="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>All Cause Mortality</title>
        <description>In-hospital mortality</description>
        <time_frame>duration of hospitalization (an average of 2 weeks)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Furosemide</title>
            <description>Patients randomized to furosemide</description>
          </group>
          <group group_id="O2">
            <title>Peritoneal Dialysis</title>
            <description>Patients randomized to peritoneal dialysis</description>
          </group>
        </group_list>
        <measure>
          <title>All Cause Mortality</title>
          <description>In-hospital mortality</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="32"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Renal/Electrolyte Abnormalities</title>
        <description>Total sum of renal and electrolyte abnormalities over the first 5 postoperative days as defined in the protocol</description>
        <time_frame>Postop morning 1-5</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Furosemide</title>
            <description>Patients randomized to furosemide</description>
          </group>
          <group group_id="O2">
            <title>Peritoneal Dialysis</title>
            <description>Patients randomized to peritoneal dialysis</description>
          </group>
        </group_list>
        <measure>
          <title>Renal/Electrolyte Abnormalities</title>
          <description>Total sum of renal and electrolyte abnormalities over the first 5 postoperative days as defined in the protocol</description>
          <units>abnormalities</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6" lower_limit="4" upper_limit="7"/>
                    <measurement group_id="O2" value="4" lower_limit="3" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Doses of Potassium Chloride or Arginine Chloride Required</title>
        <description>Total doses of potassium chloride or arginine chloride given during the first five postoperative days.</description>
        <time_frame>Postop day 0-5</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Furosemide</title>
            <description>Patients randomized to furosemide</description>
          </group>
          <group group_id="O2">
            <title>Peritoneal Dialysis</title>
            <description>Patients randomized to peritoneal dialysis</description>
          </group>
        </group_list>
        <measure>
          <title>Doses of Potassium Chloride or Arginine Chloride Required</title>
          <description>Total doses of potassium chloride or arginine chloride given during the first five postoperative days.</description>
          <units>doses given</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="1" upper_limit="5"/>
                    <measurement group_id="O2" value="1" lower_limit="0" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>B-Natriuretic Peptide</title>
        <description>BNP measured at 24 and 48 hours postoperatively</description>
        <time_frame>At 24hours and 48 hours postoperative</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Furosemide</title>
            <description>Patients randomized to furosemide</description>
          </group>
          <group group_id="O2">
            <title>Peritoneal Dialysis</title>
            <description>Patients randomized to peritoneal dialysis</description>
          </group>
        </group_list>
        <measure>
          <title>B-Natriuretic Peptide</title>
          <description>BNP measured at 24 and 48 hours postoperatively</description>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1334" lower_limit="901" upper_limit="2764"/>
                    <measurement group_id="O2" value="1168" lower_limit="555" upper_limit="2439"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1110" lower_limit="611" upper_limit="2221"/>
                    <measurement group_id="O2" value="663" lower_limit="486" upper_limit="1593"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Modified Oxygenation Index</title>
        <description>Product of Mean airway pressure delivered by mechanical ventilation and FiO2 of administered oxygen</description>
        <time_frame>at 24 and 48 hours postoperative</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Furosemide</title>
            <description>Patients randomized to furosemide</description>
          </group>
          <group group_id="O2">
            <title>Peritoneal Dialysis</title>
            <description>Patients randomized to PD</description>
          </group>
        </group_list>
        <measure>
          <title>Modified Oxygenation Index</title>
          <description>Product of Mean airway pressure delivered by mechanical ventilation and FiO2 of administered oxygen</description>
          <units>Units</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 Hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="3.2" upper_limit="5.2"/>
                    <measurement group_id="O2" value="4" lower_limit="0.03" upper_limit="5.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 Hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" lower_limit="2.4" upper_limit="5.4"/>
                    <measurement group_id="O2" value="2.8" lower_limit="2.2" upper_limit="4.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Furosemide</title>
          <description>Patients randomized to furosemide</description>
        </group>
        <group group_id="E2">
          <title>Peritoneal Dialysis</title>
          <description>Patients randomized to peritoneal dialysis</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="32"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Bleeding Event</sub_title>
                <description>Bleeding from PD catheter or relating to its placement requiring blood product transfusion.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hydrocele</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <description>Development of hydrocele</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>
    <point_of_contact>
      <name_or_title>David Kwiatkowski</name_or_title>
      <organization>Stanford University</organization>
      <phone>650-721-3290</phone>
      <email>david.kwiatkowski@stanford.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/NCT01709227
org study id: 2011-1730
nct id: NCT01709227
lead sponsor: 
has dmc: Yes
Acute kidney injury (AKI) after cardiopulmonary bypass (CPB) in infants is common and
      associated with poor outcomes. Peritoneal dialysis (PD) and furosemide have been used to
      attain negative fluid balance due to AKI induced oliguria, but have not been compared
      prospectively. The investigators will prospectively compare outcomes of infants with oliguria
      after CPB randomized to PD vs. furosemide with the hypothesis that infants receiving PD have
      superior outcomes.
Background: Acute kidney injury (AKI) is a common postoperative complication after heart
      surgery with cardiopulmonary bypass (CPB). Multiple studies have demonstrated that patients
      with AKI have worse clinical outcomes, such as longer ventilation times and increased length
      of stay, which is thought to be secondary to associated oliguria and subsequent fluid
      overload. Studies suggest that early renal replacement therapy (RRT) via peritoneal dialysis
      (PD) may prevent fluid overload and therefore be a superior management to diuretic (i.e.
      furosemide) administration. However, there is no published evidence to suggest superiority or
      laboratory data available to guide decision making.

      Objective: Our primary objective is to determine if early institution of PD improves clinical
      outcomes compared to administration of furosemide in post-operative cardiac infants with
      acute kidney injury. We hypothesize that early initiation of PD will improve clinical
      outcomes. We will determine if these clinical outcomes will be better among good responders
      of furosemide compared to poor responders. We will determine if postoperative NGAL
      concentrations are predictive of poor response to furosemide.

      Design / Methods: The study will be a single-center randomized clinical trial among neonates
      undergoing cardiac surgery with CPB with planned placement of a PD catheter due to risk of
      AKI. If patients demonstrate oliguria within the first postoperative day, they will be
      randomized to early PD or trial of furosemide. Clinical and laboratory data will be collected
      and compared between groups.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Negative Fluid Balance on Postop Day 1
time frame: Postop day 1
description: Difference of inputs and outputs, including urine output and PD drainage.
measure: Respiratory Support Administered
time frame: Duration of postoperative intubation (average time approximately- 1 week)
description: Duration of initial course of postoperative mechanical ventilation
measure: NGAL Concentration
time frame: Pre-op, and postop (2hr, 6hr, 12hr, 24hr, 48hr)
measure: Duration of Cardiac ICU Stay
time frame: Average 2 weeks
description: Total days of initial postoperative stay in cardiac ICU
measure: Duration of Hospital Stay
time frame: Average 4 weeks
description: Total days of initial postoperative stay in hospital
measure: All Cause Mortality
time frame: duration of hospitalization (an average of 2 weeks)
description: In-hospital mortality
measure: Renal/Electrolyte Abnormalities
time frame: Postop morning 1-5
description: Total sum of renal and electrolyte abnormalities over the first 5 postoperative days as defined in the protocol
measure: Doses of Potassium Chloride or Arginine Chloride Required
time frame: Postop day 0-5
description: Total doses of potassium chloride or arginine chloride given during the first five postoperative days.
measure: B-Natriuretic Peptide
time frame: At 24hours and 48 hours postoperative
description: BNP measured at 24 and 48 hours postoperatively
measure: Modified Oxygenation Index
time frame: at 24 and 48 hours postoperative
description: Product of Mean airway pressure delivered by mechanical ventilation and FiO2 of administered oxygen
arm group label: Furosemide
arm group type: Experimental
description: Patients randomized to the furosemide arm will be given 1 mg/kg intravenously every 6 hours for 2 doses and then as directed by CICU attending to augment urine output. Patients within this arm who have urine output <1 ml/kg/hr over 16 hours after the first dose of Lasix will be considered poor responders. These patients may be started on PD if clinically indicated. Those who show good response (urine output >1 ml/kg/hr over subsequent 16 hours) will continue furosemide as needed to augment urine output. If they subsequently develop oliguria or fluid overload unresponsive to diuretic therapy, these patients may later be started on PD at discretion of CICU attending with consultation of nephrology service.
arm group label: Peritoneal dialysis
arm group type: Experimental
description: Patients within the PD arm will begin PD with a standardized dialysis plan of 10ml/kg of 1.5% Dianeal™ with 1 hours cycles (5 minute fill, 45 minute dwell and 10 minute drain). Further PD management will be directed by CICU attending and Nephrology service
intervention type: Drug
intervention name: Furosemide
description: Patients randomized to the furosemide arm will be given 1 mg/kg intravenously every 6 hours for 2 doses and then as directed by CICU attending to augment urine output. Patients within this arm who have urine output <1 ml/kg/hr over 16 hours after the first dose of Lasix will be considered poor responders. These patients may be started on PD if clinically indicated. Those who show good response (urine output >1 ml/kg/hr over subsequent 16 hours) will continue furosemide as needed to augment urine output. If they subsequently develop oliguria or fluid overload unresponsive to diuretic therapy, these patients may later be started on PD at discretion of CICU attending with consultation of nephrology service.
arm group label: Furosemide
other name: Lasix
intervention type: Procedure
intervention name: Peritoneal Dialysis
description: Patients within the PD arm will begin PD with a standardized dialysis plan of 10ml/kg of 1.5% Dianeal™ with 1 hours cycles (5 minute fill, 45 minute dwell and 10 minute drain). Further PD management and discontinuation will be directed by CICU attending and Nephrology service.
arm group label: Peritoneal dialysis
other name: PD
criteria: 
gender: All
minimum age: N/A
maximum age: 6 Months
healthy volunteers: No
last name: David M Kwiatkowski, MD
role: Principal Investigator
affiliation: Cinncinnati Children's Hospital Medical Center
last name: Catherine D Krawczeski, MD
role: Study Director
affiliation: Cinncinnati Children's Hospital Medical Center
last name: Stuart L Goldstein, MD
role: Study Director
affiliation: Cinncinnati Children's Hospital Medical Center
facility: 
country: United States
url: http://www.cincinnatichildrens.org/service/c/cacn/default/
description: Center for Acute Care Nephology at Cincinnati Childrens
responsible party type: Sponsor
mesh term: Acute Kidney Injury
mesh term: Furosemide
sharing ipd: Yes
ipd description: De-identified patient data would be available to other researchers after publication of data at the discretion of the research team after communication with the PI
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 