<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/NCT02214186</url>
  </required_header>
  <id_info>
    <org_study_id>CAPPesq 675.011</org_study_id>
    <nct_id>NCT02214186</nct_id>
  </id_info>
  <brief_title>Restrictive Fluid Therapy in Severe Preeclampsia</brief_title>
  <official_title>Impact of Restrictive Fluid Therapy on Renal Function in Severe Preeclamptic Women Submitted to Cesarean Section Under Spinal Anesthesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Sao Paulo General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Introduction: Pre-eclampsia is a multifactorial syndrome which occurs in hypertension and&#xD;
      proteinuria in pregnant women over 20 weeks gestation. It is the leading cause of maternal&#xD;
      complications such as pulmonary edema, which occurs in about 3% of severe preeclamptic having&#xD;
      as one of the causes volume overload. Anesthetic procedures are frequent in this population,&#xD;
      with replacement with crystalloid of the duct during cesarean section under spinal anesthesia&#xD;
      for combat hypotension and hypovolemia manifested by oliguria. However, as water therapy have&#xD;
      antagonistic effects on cardiopulmonary and renal systems is no doubt as to the benefits&#xD;
      compared to conventional or restrictive pattern of fluid therapy on renal function.&#xD;
      Objective: To compare the renal function of patients with severe preeclampsia who received&#xD;
      restrictive fluid therapy during caesarean section, as well as evaluating the use of cystatin&#xD;
      C and Neutrophil gelatinase-associated lipocalin (NGAL) as a predictor of renal damage in&#xD;
      this population. Hypothesis: Intraoperative fluid restriction did not influence renal&#xD;
      function of patients with severe preeclampsia undergoing cesarean section under spinal&#xD;
      anesthesia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preeclampsia (PE) is the leading cause of morbidity and mortality worldwide during pregnancy.&#xD;
      Fluid therapy for PE women during cesarean section is a controversial issue among medical&#xD;
      specialists.&#xD;
&#xD;
      The replacement with crystalloid fluids tool is traditionally used by anesthesiologists&#xD;
      during cesarean section under spinal anesthesia for combat hypotension and hypovolemia&#xD;
      manifested by oliguria. However, as crystalloid infusion has antagonistic effects on&#xD;
      cardiopulmonary and renal systems, there is controversy regarding benefits over conventional&#xD;
      and restrictive fluid therapy. Therefore, due to cardiovascular changes in severe PE,&#xD;
      restrictive fluid therapy could possibly be beneficial, avoiding complications such as acute&#xD;
      pulmonary edema.&#xD;
&#xD;
      Currently, volume replacement during cesarean section in these patients is performed with&#xD;
      volumes of about 1500 ml of crystalloid to decrease the chance of developing kidney injury or&#xD;
      aggravating previous injury. However, it is not known in the literature whether the renal&#xD;
      lesions that appear after birth in patients with PE are just due to the course of the disease&#xD;
      itself or can be modified by fluid restriction during the conduct of anesthesia cesarean.&#xD;
&#xD;
      Moreover, intraoperative fluid restriction (250 ml crystalloid) appears as an alternative to&#xD;
      handling the patient with PEG, as already safely used in cardiac patients, such as patients&#xD;
      with mitral valve stenosis. The security of fluid restriction in patients with PE comes from&#xD;
      the fact that pre-eclamptic suffer fewer episodes of hypotension during cesarean section&#xD;
      under spinal anesthesia, requiring less fluid input for this purpose. In addition, the&#xD;
      pathophysiology of this disease points to a relative hypovolemia, once the delivery&#xD;
      performed, with removal of the placenta, fluids kidnapped in excess to third space (tissue&#xD;
      edema) will be redirected to the intravascular compartment, restoring homeostasis.&#xD;
&#xD;
      Cystatin C and NGAL (Neutrophil gelatinase-associated lipocalin) arise as valid tools to&#xD;
      predict the degree of renal injury. These molecules arise before the onset of renal injury,&#xD;
      providing diagnostic and therapeutic actions that can reduce morbidity and mortality related&#xD;
      to kidney failure, since some studies have shown that women in first pregnancy with PE are&#xD;
      more likely to develop chronic kidney disease that pregnant women without PE.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2014</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">March 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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy</measure>
    <time_frame>preoperative, first and second day postoperative</time_frame>
    <description>Renal function evaluated through creatinine levels in three moments: preoperative, first and second postoperative days.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) Index</measure>
    <time_frame>Postoperative renal dysfunction</time_frame>
    <description>Renal dysfunction was stratified by the Acute Kidney Injury Network (AKIN) index in three stages, in terms of creatinine increase from baseline: stage 1 included an interval of 150-200%, stage 2 200%-300%, and stage 3 more than 300% or hemodialysis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in Preeclampsia</measure>
    <time_frame>preoperative, first and second day postoperative</time_frame>
    <description>Evaluate new marker of renal injury (NGAL) in the specific population of patients with severe preeclampsia, comparing the values of first and second postoperative days to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cystatin C as New Marker of Renal Injury in Preeclampsia</measure>
    <time_frame>preoperative, first and second day postoperative</time_frame>
    <description>Evaluate new marker of renal injury (Cystatin C) in the specific population of patients with severe preeclampsia, comparing the values of first and second postoperative days to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of Hydration</measure>
    <time_frame>Proteinuria in severe pre-eclampsia in in pre-operative and post-operative period</time_frame>
    <description>Proteinuria in severe pre-eclampsia submitted to cesarean section under different regimes of hydration. Analyses in pre-operative and post-operative period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelets in Restrictive Fluid Management of Severe Preeclampsia</measure>
    <time_frame>preoperative, first and second day postoperative</time_frame>
    <description>Compare platelets count in the restrictive and liberal groups during the first and second post-operative days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>International Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section</measure>
    <time_frame>preoperative, first and second day postoperative</time_frame>
    <description>Compare International Normalized Ratio (INR) of Prothrombin Time (PT) in the restrictive and liberal groups in preoperative, first and second day postoperative.&#xD;
PT is expressed in seconds and the entered values represented the INR of PT among study participants and a control population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section</measure>
    <time_frame>preoperative, first and second day postoperative</time_frame>
    <description>Compare activated partial thromboplastin time (APPT) and relation with control (R) in the restrictive and liberal groups.&#xD;
APPT is a laboratory test that evaluates the efficiency of the intrinsic pathway of coagulation. The unit of measure is seconds and the results are presented as relation (R) with control.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Urine Output During Cesarean Section in Severe Pre-eclampsia</measure>
    <time_frame>urine output during cesarean section (an average of 60 minutes)</time_frame>
    <description>Urine output during cesarean section in severe pre-eclampsia under two different regimes of hydration (restrictive and liberal)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Pre-Eclampsia</condition>
  <arm_group>
    <arm_group_label>Liberal Fluid therapy</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Restrictive Fluid Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The restrictive group will receive 250 mL of crystalloid solution during cesarean section.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Restrictive Fluid Therapy</intervention_name>
    <description>The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.</description>
    <arm_group_label>Restrictive Fluid Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Severe PE was defined as at least one of the following criteria: systolic pressure&#xD;
             ≥160 mmHg or diastolic pressure ≥110 mmHg, severe proteinuria (&gt;5 g/24 h), oliguria&#xD;
             (&lt;500 ml/24 h), cerebral or visual disturbances, pulmonary edema, epigastric pain,&#xD;
             hepatic rupture, impaired liver function, thrombocytopenia, hemolysis, elevated liver&#xD;
             enzymes and low platelet count (HELLP) syndrome and evidence of fetal compromise.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous serum creatinine levels &gt;1 mg/dl&#xD;
&#xD;
          -  previous kidney disease&#xD;
&#xD;
          -  contraindication to spinal anesthesia&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wallace A Da Silva, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital das Clínicas da Faculdade de Medicina da USP</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Fernando Bliacheriene, PHD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital das Clínicas da Faculdade de Medicina da USP</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Maria José C Carmona, PHD</last_name>
    <role>Study Director</role>
    <affiliation>Hospital das Clínicas da Faculdade de Medicina da USP</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Carlo Victor A Varela, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital das Clínicas da Faculdade de Medicina da USP</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Paula C Scherer, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital das Clínicas da Faculdade de Medicina da USP</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marcelo Luis A Torres, PHD</last_name>
    <role>Study Director</role>
    <affiliation>Hospital das Clínicas da Faculdade de Medicina da USP</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital das Clínicas da Faculdade de Medicina da USP</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>01246903</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005 Feb 26-Mar 4;365(9461):785-99. doi: 10.1016/S0140-6736(05)17987-2.</citation>
    <PMID>15733721</PMID>
  </reference>
  <reference>
    <citation>Sibai BM, Mabie WC. Hemodynamics of preeclampsia. Clin Perinatol. 1991 Dec;18(4):727-47.</citation>
    <PMID>1764880</PMID>
  </reference>
  <reference>
    <citation>Aya AGM, Mangin R, Vialles N, Ferrer JM, Robert C, Ripart J, de La Coussaye JE. Patients with severe preeclampsia experience less hypotension during spinal anesthesia for elective cesarean delivery than healthy parturients: a prospective cohort comparison. Anesth Analg. 2003 Sep;97(3):867-872. doi: 10.1213/01.ANE.0000073610.23885.F2.</citation>
    <PMID>12933418</PMID>
  </reference>
  <reference>
    <citation>Pan PH, D'Angelo R. Anesthetic and analgesic management of mitral stenosis during pregnancy. Reg Anesth Pain Med. 2004 Nov-Dec;29(6):610-5. doi: 10.1016/j.rapm.2004.09.006. No abstract available.</citation>
    <PMID>15635522</PMID>
  </reference>
  <reference>
    <citation>Dyer RA, Piercy JL, Reed AR, Lombard CJ, Schoeman LK, James MF. Hemodynamic changes associated with spinal anesthesia for cesarean delivery in severe preeclampsia. Anesthesiology. 2008 May;108(5):802-11. doi: 10.1097/01.anes.0000311153.84687.c7.</citation>
    <PMID>18431115</PMID>
  </reference>
  <reference>
    <citation>Mabie WC, Ratts TE, Sibai BM. The central hemodynamics of severe preeclampsia. Am J Obstet Gynecol. 1989 Dec;161(6 Pt 1):1443-8. doi: 10.1016/0002-9378(89)90901-0.</citation>
    <PMID>2603896</PMID>
  </reference>
  <reference>
    <citation>Dennis AT, Solnordal CB. Acute pulmonary oedema in pregnant women. Anaesthesia. 2012 Jun;67(6):646-59. doi: 10.1111/j.1365-2044.2012.07055.x. Epub 2012 Mar 15.</citation>
    <PMID>22420683</PMID>
  </reference>
  <reference>
    <citation>Aya AG, Vialles N, Ripart J. [Anesthesia and preeclampsia]. Ann Fr Anesth Reanim. 2010 May;29(5):e141-7. doi: 10.1016/j.annfar.2010.03.014. Epub 2010 May 15. French.</citation>
    <PMID>20478690</PMID>
  </reference>
  <reference>
    <citation>Urbschat A, Obermuller N, Haferkamp A. Biomarkers of kidney injury. Biomarkers. 2011 Jul;16 Suppl 1:S22-30. doi: 10.3109/1354750X.2011.587129.</citation>
    <PMID>21707441</PMID>
  </reference>
  <reference>
    <citation>Vikse BE, Irgens LM, Leivestad T, Skjaerven R, Iversen BM. Preeclampsia and the risk of end-stage renal disease. N Engl J Med. 2008 Aug 21;359(8):800-9. doi: 10.1056/NEJMoa0706790.</citation>
    <PMID>18716297</PMID>
  </reference>
  <reference>
    <citation>Xin C, Yulong X, Yu C, Changchun C, Feng Z, Xinwei M. Urine neutrophil gelatinase-associated lipocalin and interleukin-18 predict acute kidney injury after cardiac surgery. Ren Fail. 2008;30(9):904-13. doi: 10.1080/08860220802359089.</citation>
    <PMID>18925531</PMID>
  </reference>
  <reference>
    <citation>Martensson J, Martling CR, Oldner A, Bell M. Impact of sepsis on levels of plasma cystatin C in AKI and non-AKI patients. Nephrol Dial Transplant. 2012 Feb;27(2):576-81. doi: 10.1093/ndt/gfr358. Epub 2011 Sep 12.</citation>
    <PMID>21765189</PMID>
  </reference>
  <reference>
    <citation>Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A; Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31. doi: 10.1186/cc5713.</citation>
    <PMID>17331245</PMID>
  </reference>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 16, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 12, 2014</study_first_posted>
  <results_first_submitted>July 6, 2015</results_first_submitted>
  <results_first_submitted_qc>August 7, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">September 7, 2015</results_first_posted>
  <last_update_submitted>January 16, 2017</last_update_submitted>
  <last_update_submitted_qc>January 16, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pre-Eclampsia</keyword>
  <keyword>Acute Kidney Injury</keyword>
  <keyword>Fluid Therapy</keyword>
  <keyword>Anesthesia, Spinal</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Eclampsia</mesh_term>
    <mesh_term>Pre-Eclampsia</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>We calculated the total sample size from a pilot study. Assuming a power of 80% and 95% confidence, the sample necessary to conduct the study was 21 patients in each group of interest. As we considered 10% as maximum margin of loss during follow-up, there were 23 patients enrolled in each group.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Liberal Fluid Therapy</title>
          <description>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.</description>
        </group>
        <group group_id="P2">
          <title>Restrictive Fluid Therapy</title>
          <description>The restrictive group will receive 250 mL of crystalloid solution during cesarean section.&#xD;
Restrictive Fluid Therapy: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Liberal Fluid Therapy</title>
          <description>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.</description>
        </group>
        <group group_id="B2">
          <title>Restrictive Fluid Therapy</title>
          <description>The restrictive group will receive 250 mL of crystalloid solution during cesarean section.&#xD;
Restrictive Fluid Therapy: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.</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="23"/>
            <count group_id="B2" value="23"/>
            <count group_id="B3" value="46"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31" spread="8"/>
                    <measurement group_id="B2" value="33" spread="5"/>
                    <measurement group_id="B3" value="32.07" spread="6.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</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="23"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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>Gestational age (weeks)</title>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36.9" lower_limit="35.3" upper_limit="37.0"/>
                    <measurement group_id="B2" value="36.7" lower_limit="30.1" upper_limit="37.4"/>
                    <measurement group_id="B3" value="36.8" lower_limit="33" upper_limit="37.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body mass index (kg/m2)</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33.78" spread="7.17"/>
                    <measurement group_id="B2" value="31.98" spread="5.58"/>
                    <measurement group_id="B3" value="32.88" spread="6.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Twin pregnancy</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Chronic hypertension</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Previous preeclampsia</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diabetes Mellitus</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Systolic blood pressure (mmHg)</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="161" spread="17"/>
                    <measurement group_id="B2" value="170" spread="20"/>
                    <measurement group_id="B3" value="165.5" spread="18.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diastolic blood pressure (mmHg)</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="100.05" spread="11.75"/>
                    <measurement group_id="B2" value="104.80" spread="15.75"/>
                    <measurement group_id="B3" value="102.42" spread="13.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy</title>
        <description>Renal function evaluated through creatinine levels in three moments: preoperative, first and second postoperative days.</description>
        <time_frame>preoperative, first and second day postoperative</time_frame>
        <population>Were included in the analysis the patients who violated the protocol and lost follow-up (intention to treat analysis)</population>
        <group_list>
          <group group_id="O1">
            <title>Liberal Fluid Therapy</title>
            <description>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.</description>
          </group>
          <group group_id="O2">
            <title>Restrictive Fluid Therapy</title>
            <description>The restrictive group will receive 250 mL of crystalloid solution during cesarean section.&#xD;
Restrictive Fluid Therapy: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy</title>
          <description>Renal function evaluated through creatinine levels in three moments: preoperative, first and second postoperative days.</description>
          <population>Were included in the analysis the patients who violated the protocol and lost follow-up (intention to treat analysis)</population>
          <units>mg/dl</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="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Creatinine preoperative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.69" lower_limit="0.55" upper_limit="0.83"/>
                    <measurement group_id="O2" value="0.73" lower_limit="0.55" upper_limit="0.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine 1st post-operative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.99" lower_limit="0.80" upper_limit="1.22"/>
                    <measurement group_id="O2" value="0.93" lower_limit="0.76" upper_limit="1.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine 2nd post-operative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.96" lower_limit="0.80" upper_limit="1.09"/>
                    <measurement group_id="O2" value="0.84" lower_limit="0.69" upper_limit="1.08"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <method_desc>Mann-Whitney followed by Friedman test</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Neutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in Preeclampsia</title>
        <description>Evaluate new marker of renal injury (NGAL) in the specific population of patients with severe preeclampsia, comparing the values of first and second postoperative days to baseline.</description>
        <time_frame>preoperative, first and second day postoperative</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liberal Fluid Therapy</title>
            <description>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.</description>
          </group>
          <group group_id="O2">
            <title>Restrictive Fluid Therapy</title>
            <description>The restrictive group will receive 250 mL of crystalloid solution during cesarean section.&#xD;
Restrictive Fluid Therapy: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Neutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in Preeclampsia</title>
          <description>Evaluate new marker of renal injury (NGAL) in the specific population of patients with severe preeclampsia, comparing the values of first and second postoperative days to baseline.</description>
          <units>mg/L</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="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>NGAL preoperative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.16" lower_limit="0.10" upper_limit="0.20"/>
                    <measurement group_id="O2" value="0.15" lower_limit="0.13" upper_limit="0.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>NGAL 1st post-operative day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.18" lower_limit="0.13" upper_limit="026"/>
                    <measurement group_id="O2" value="0.21" lower_limit="0.16" upper_limit="0.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>NGAL 2nd post-operative day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.15" lower_limit="0.10" upper_limit="0.24"/>
                    <measurement group_id="O2" value="0.15" lower_limit="0.11" upper_limit="0.22"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <method_desc>Mann-Whitney followed by Friedman test</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cystatin C as New Marker of Renal Injury in Preeclampsia</title>
        <description>Evaluate new marker of renal injury (Cystatin C) in the specific population of patients with severe preeclampsia, comparing the values of first and second postoperative days to baseline.</description>
        <time_frame>preoperative, first and second day postoperative</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liberal Fluid Therapy</title>
            <description>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.</description>
          </group>
          <group group_id="O2">
            <title>Restrictive Fluid Therapy</title>
            <description>The restrictive group will receive 250 mL of crystalloid solution during cesarean section.&#xD;
Restrictive Fluid Therapy: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Cystatin C as New Marker of Renal Injury in Preeclampsia</title>
          <description>Evaluate new marker of renal injury (Cystatin C) in the specific population of patients with severe preeclampsia, comparing the values of first and second postoperative days to baseline.</description>
          <units>mg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cyst C preoperative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.73" spread="0.6"/>
                    <measurement group_id="O2" value="1.99" spread="0.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cyst C 1st postoperative day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.93" spread="0.8"/>
                    <measurement group_id="O2" value="2.03" spread="0.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cyst C 2nd postoperative day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.64" spread="0.5"/>
                    <measurement group_id="O2" value="1.72" spread="0.43"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>ANOVA</method>
            <method_desc>ANOVA for repeated measures</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of Hydration</title>
        <description>Proteinuria in severe pre-eclampsia submitted to cesarean section under different regimes of hydration. Analyses in pre-operative and post-operative period.</description>
        <time_frame>Proteinuria in severe pre-eclampsia in in pre-operative and post-operative period</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liberal Fluid Therapy</title>
            <description>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.</description>
          </group>
          <group group_id="O2">
            <title>Restrictive Fluid Therapy</title>
            <description>The restrictive group will receive 250 mL of crystalloid solution during cesarean section.&#xD;
Restrictive Fluid Therapy: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of Hydration</title>
          <description>Proteinuria in severe pre-eclampsia submitted to cesarean section under different regimes of hydration. Analyses in pre-operative and post-operative period.</description>
          <units>g/dl</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="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Proteinuria pre-operative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.46" lower_limit="0.32" upper_limit="1.71"/>
                    <measurement group_id="O2" value="2.62" lower_limit="0.80" upper_limit="9.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Proteinuria 1st post-operative day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.15" lower_limit="0.10" upper_limit="0.88"/>
                    <measurement group_id="O2" value="0.40" lower_limit="0.28" upper_limit="0.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Proteinuria 2nd post-operative day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.20" lower_limit="0.10" upper_limit="0.48"/>
                    <measurement group_id="O2" value="0.45" lower_limit="0.10" upper_limit="2.23"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <method_desc>Mann-Whitney followed by Friedman test</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelets in Restrictive Fluid Management of Severe Preeclampsia</title>
        <description>Compare platelets count in the restrictive and liberal groups during the first and second post-operative days.</description>
        <time_frame>preoperative, first and second day postoperative</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liberal Fluid Therapy</title>
            <description>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.</description>
          </group>
          <group group_id="O2">
            <title>Restrictive Fluid Therapy</title>
            <description>The restrictive group will receive 250 mL of crystalloid solution during cesarean section.&#xD;
Restrictive Fluid Therapy: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Platelets in Restrictive Fluid Management of Severe Preeclampsia</title>
          <description>Compare platelets count in the restrictive and liberal groups during the first and second post-operative days.</description>
          <units>thrombocytes/mm3</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Platelets preoperative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="194400" spread="77867"/>
                    <measurement group_id="O2" value="207941" spread="71371"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelets 1st postoperative day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="183250" spread="83234"/>
                    <measurement group_id="O2" value="201118" spread="61687"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelets 2nd postoperative day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="192850" spread="80692"/>
                    <measurement group_id="O2" value="221824" spread="62925"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&gt;0.05</p_value>
            <method>ANOVA</method>
            <method_desc>ANOVA for repeated measures.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>International Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section</title>
        <description>Compare International Normalized Ratio (INR) of Prothrombin Time (PT) in the restrictive and liberal groups in preoperative, first and second day postoperative.&#xD;
PT is expressed in seconds and the entered values represented the INR of PT among study participants and a control population.</description>
        <time_frame>preoperative, first and second day postoperative</time_frame>
        <population>The values are expressed in seconds and presented as a ration (INR) with control patients.</population>
        <group_list>
          <group group_id="O1">
            <title>Liberal Fluid Therapy</title>
            <description>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.</description>
          </group>
          <group group_id="O2">
            <title>Restrictive Fluid Therapy</title>
            <description>The restrictive group will receive 250 mL of crystalloid solution during cesarean section.&#xD;
Restrictive Fluid Therapy: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>International Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section</title>
          <description>Compare International Normalized Ratio (INR) of Prothrombin Time (PT) in the restrictive and liberal groups in preoperative, first and second day postoperative.&#xD;
PT is expressed in seconds and the entered values represented the INR of PT among study participants and a control population.</description>
          <population>The values are expressed in seconds and presented as a ration (INR) with control patients.</population>
          <units>ratio</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="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PT/INR preoperative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00" lower_limit="0.95" upper_limit="1.10"/>
                    <measurement group_id="O2" value="0.95" lower_limit="0.95" upper_limit="0.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PT/INR first post-operative day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.03" lower_limit="0.95" upper_limit="1.09"/>
                    <measurement group_id="O2" value="0.95" lower_limit="0.95" upper_limit="0.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PT/INR seconde post-operative day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0.97" upper_limit="1.07"/>
                    <measurement group_id="O2" value="0.95" lower_limit="0.95" upper_limit="0.95"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <method_desc>Mann-Whitney followed by Friedman test</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Urine Output During Cesarean Section in Severe Pre-eclampsia</title>
        <description>Urine output during cesarean section in severe pre-eclampsia under two different regimes of hydration (restrictive and liberal)</description>
        <time_frame>urine output during cesarean section (an average of 60 minutes)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liberal Fluid Therapy</title>
            <description>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.</description>
          </group>
          <group group_id="O2">
            <title>Restrictive Fluid Therapy</title>
            <description>The restrictive group will receive 250 mL of crystalloid solution during cesarean section.&#xD;
Restrictive Fluid Therapy: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Urine Output During Cesarean Section in Severe Pre-eclampsia</title>
          <description>Urine output during cesarean section in severe pre-eclampsia under two different regimes of hydration (restrictive and liberal)</description>
          <units>ml/h</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="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="116" lower_limit="69" upper_limit="191"/>
                    <measurement group_id="O2" value="80" lower_limit="37" upper_limit="110"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section</title>
        <description>Compare activated partial thromboplastin time (APPT) and relation with control (R) in the restrictive and liberal groups.&#xD;
APPT is a laboratory test that evaluates the efficiency of the intrinsic pathway of coagulation. The unit of measure is seconds and the results are presented as relation (R) with control.</description>
        <time_frame>preoperative, first and second day postoperative</time_frame>
        <population>The values are expressed in seconds and presented as a ration (R) with control patients.</population>
        <group_list>
          <group group_id="O1">
            <title>Liberal Fluid Therapy</title>
            <description>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.</description>
          </group>
          <group group_id="O2">
            <title>Restrictive Fluid Therapy</title>
            <description>The restrictive group will receive 250 mL of crystalloid solution during cesarean section.&#xD;
Restrictive Fluid Therapy: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section</title>
          <description>Compare activated partial thromboplastin time (APPT) and relation with control (R) in the restrictive and liberal groups.&#xD;
APPT is a laboratory test that evaluates the efficiency of the intrinsic pathway of coagulation. The unit of measure is seconds and the results are presented as relation (R) with control.</description>
          <population>The values are expressed in seconds and presented as a ration (R) with control patients.</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>APPT/R preoperative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.98" spread="0.13"/>
                    <measurement group_id="O2" value="1.01" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>APPT/R 1st post-operative day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.07" spread="0.10"/>
                    <measurement group_id="O2" value="1.03" spread="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>APPT/R 2nd post-operative day</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.07" spread="0.13"/>
                    <measurement group_id="O2" value="1.01" spread="0.07"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>ANOVA</method>
            <method_desc>ANOVA for repeated measures.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) Index</title>
        <description>Renal dysfunction was stratified by the Acute Kidney Injury Network (AKIN) index in three stages, in terms of creatinine increase from baseline: stage 1 included an interval of 150-200%, stage 2 200%-300%, and stage 3 more than 300% or hemodialysis</description>
        <time_frame>Postoperative renal dysfunction</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Liberal Fluid Therapy</title>
            <description>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.</description>
          </group>
          <group group_id="O2">
            <title>Restrictive Fluid Therapy</title>
            <description>The restrictive group will receive 250 mL of crystalloid solution during cesarean section.&#xD;
Restrictive Fluid Therapy: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) Index</title>
          <description>Renal dysfunction was stratified by the Acute Kidney Injury Network (AKIN) index in three stages, in terms of creatinine increase from baseline: stage 1 included an interval of 150-200%, stage 2 200%-300%, and stage 3 more than 300% or hemodialysis</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AKIN stage I</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AKIN stage II</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AKIN stage III</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Possible adverse event were observed during the first and second post-operative days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Liberal Fluid Therapy</title>
          <description>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.</description>
        </group>
        <group group_id="E2">
          <title>Restrictive Fluid Therapy</title>
          <description>The restrictive group will receive 250 mL of crystalloid solution during cesarean section.&#xD;
Restrictive Fluid Therapy: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
              </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="21"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
              </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>M.D. Wallace Andrino da Silva</name_or_title>
      <organization>Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo</organization>
      <phone>+551126616787</phone>
      <email>wallaceandrino@yahoo.com.br</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/NCT02214186
org study id: CAPPesq 675.011
nct id: NCT02214186
lead sponsor: 
has dmc: Yes
Introduction: Pre-eclampsia is a multifactorial syndrome which occurs in hypertension and
      proteinuria in pregnant women over 20 weeks gestation. It is the leading cause of maternal
      complications such as pulmonary edema, which occurs in about 3% of severe preeclamptic having
      as one of the causes volume overload. Anesthetic procedures are frequent in this population,
      with replacement with crystalloid of the duct during cesarean section under spinal anesthesia
      for combat hypotension and hypovolemia manifested by oliguria. However, as water therapy have
      antagonistic effects on cardiopulmonary and renal systems is no doubt as to the benefits
      compared to conventional or restrictive pattern of fluid therapy on renal function.
      Objective: To compare the renal function of patients with severe preeclampsia who received
      restrictive fluid therapy during caesarean section, as well as evaluating the use of cystatin
      C and Neutrophil gelatinase-associated lipocalin (NGAL) as a predictor of renal damage in
      this population. Hypothesis: Intraoperative fluid restriction did not influence renal
      function of patients with severe preeclampsia undergoing cesarean section under spinal
      anesthesia.
Preeclampsia (PE) is the leading cause of morbidity and mortality worldwide during pregnancy.
      Fluid therapy for PE women during cesarean section is a controversial issue among medical
      specialists.

      The replacement with crystalloid fluids tool is traditionally used by anesthesiologists
      during cesarean section under spinal anesthesia for combat hypotension and hypovolemia
      manifested by oliguria. However, as crystalloid infusion has antagonistic effects on
      cardiopulmonary and renal systems, there is controversy regarding benefits over conventional
      and restrictive fluid therapy. Therefore, due to cardiovascular changes in severe PE,
      restrictive fluid therapy could possibly be beneficial, avoiding complications such as acute
      pulmonary edema.

      Currently, volume replacement during cesarean section in these patients is performed with
      volumes of about 1500 ml of crystalloid to decrease the chance of developing kidney injury or
      aggravating previous injury. However, it is not known in the literature whether the renal
      lesions that appear after birth in patients with PE are just due to the course of the disease
      itself or can be modified by fluid restriction during the conduct of anesthesia cesarean.

      Moreover, intraoperative fluid restriction (250 ml crystalloid) appears as an alternative to
      handling the patient with PEG, as already safely used in cardiac patients, such as patients
      with mitral valve stenosis. The security of fluid restriction in patients with PE comes from
      the fact that pre-eclamptic suffer fewer episodes of hypotension during cesarean section
      under spinal anesthesia, requiring less fluid input for this purpose. In addition, the
      pathophysiology of this disease points to a relative hypovolemia, once the delivery
      performed, with removal of the placenta, fluids kidnapped in excess to third space (tissue
      edema) will be redirected to the intravascular compartment, restoring homeostasis.

      Cystatin C and NGAL (Neutrophil gelatinase-associated lipocalin) arise as valid tools to
      predict the degree of renal injury. These molecules arise before the onset of renal injury,
      providing diagnostic and therapeutic actions that can reduce morbidity and mortality related
      to kidney failure, since some studies have shown that women in first pregnancy with PE are
      more likely to develop chronic kidney disease that pregnant women without PE.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy
time frame: preoperative, first and second day postoperative
description: Renal function evaluated through creatinine levels in three moments: preoperative, first and second postoperative days.
measure: Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) Index
time frame: Postoperative renal dysfunction
description: Renal dysfunction was stratified by the Acute Kidney Injury Network (AKIN) index in three stages, in terms of creatinine increase from baseline: stage 1 included an interval of 150-200%, stage 2 200%-300%, and stage 3 more than 300% or hemodialysis
measure: Neutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in Preeclampsia
time frame: preoperative, first and second day postoperative
description: Evaluate new marker of renal injury (NGAL) in the specific population of patients with severe preeclampsia, comparing the values of first and second postoperative days to baseline.
measure: Cystatin C as New Marker of Renal Injury in Preeclampsia
time frame: preoperative, first and second day postoperative
description: Evaluate new marker of renal injury (Cystatin C) in the specific population of patients with severe preeclampsia, comparing the values of first and second postoperative days to baseline.
measure: Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of Hydration
time frame: Proteinuria in severe pre-eclampsia in in pre-operative and post-operative period
description: Proteinuria in severe pre-eclampsia submitted to cesarean section under different regimes of hydration. Analyses in pre-operative and post-operative period.
measure: Platelets in Restrictive Fluid Management of Severe Preeclampsia
time frame: preoperative, first and second day postoperative
description: Compare platelets count in the restrictive and liberal groups during the first and second post-operative days.
measure: International Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section
time frame: preoperative, first and second day postoperative
description: Compare International Normalized Ratio (INR) of Prothrombin Time (PT) in the restrictive and liberal groups in preoperative, first and second day postoperative.
PT is expressed in seconds and the entered values represented the INR of PT among study participants and a control population.
measure: Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section
time frame: preoperative, first and second day postoperative
description: Compare activated partial thromboplastin time (APPT) and relation with control (R) in the restrictive and liberal groups.
APPT is a laboratory test that evaluates the efficiency of the intrinsic pathway of coagulation. The unit of measure is seconds and the results are presented as relation (R) with control.
measure: Urine Output During Cesarean Section in Severe Pre-eclampsia
time frame: urine output during cesarean section (an average of 60 minutes)
description: Urine output during cesarean section in severe pre-eclampsia under two different regimes of hydration (restrictive and liberal)
arm group label: Liberal Fluid therapy
arm group type: No Intervention
description: The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean.
arm group label: Restrictive Fluid Therapy
arm group type: Active Comparator
description: The restrictive group will receive 250 mL of crystalloid solution during cesarean section.
intervention type: Other
intervention name: Restrictive Fluid Therapy
description: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.
arm group label: Restrictive Fluid Therapy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Wallace A Da Silva, MD
role: Principal Investigator
affiliation: Hospital das Clínicas da Faculdade de Medicina da USP
last name: Fernando Bliacheriene, PHD
role: Study Chair
affiliation: Hospital das Clínicas da Faculdade de Medicina da USP
last name: Maria José C Carmona, PHD
role: Study Director
affiliation: Hospital das Clínicas da Faculdade de Medicina da USP
last name: Carlo Victor A Varela, MD
role: Study Chair
affiliation: Hospital das Clínicas da Faculdade de Medicina da USP
last name: Paula C Scherer, MD
role: Study Chair
affiliation: Hospital das Clínicas da Faculdade de Medicina da USP
last name: Marcelo Luis A Torres, PHD
role: Study Director
affiliation: Hospital das Clínicas da Faculdade de Medicina da USP
facility: 
country: Brazil
citation: Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005 Feb 26-Mar 4;365(9461):785-99. doi: 10.1016/S0140-6736(05)17987-2.
PMID: 15733721
citation: Sibai BM, Mabie WC. Hemodynamics of preeclampsia. Clin Perinatol. 1991 Dec;18(4):727-47.
PMID: 1764880
citation: Aya AGM, Mangin R, Vialles N, Ferrer JM, Robert C, Ripart J, de La Coussaye JE. Patients with severe preeclampsia experience less hypotension during spinal anesthesia for elective cesarean delivery than healthy parturients: a prospective cohort comparison. Anesth Analg. 2003 Sep;97(3):867-872. doi: 10.1213/01.ANE.0000073610.23885.F2.
PMID: 12933418
citation: Pan PH, D'Angelo R. Anesthetic and analgesic management of mitral stenosis during pregnancy. Reg Anesth Pain Med. 2004 Nov-Dec;29(6):610-5. doi: 10.1016/j.rapm.2004.09.006. No abstract available.
PMID: 15635522
citation: Dyer RA, Piercy JL, Reed AR, Lombard CJ, Schoeman LK, James MF. Hemodynamic changes associated with spinal anesthesia for cesarean delivery in severe preeclampsia. Anesthesiology. 2008 May;108(5):802-11. doi: 10.1097/01.anes.0000311153.84687.c7.
PMID: 18431115
citation: Mabie WC, Ratts TE, Sibai BM. The central hemodynamics of severe preeclampsia. Am J Obstet Gynecol. 1989 Dec;161(6 Pt 1):1443-8. doi: 10.1016/0002-9378(89)90901-0.
PMID: 2603896
citation: Dennis AT, Solnordal CB. Acute pulmonary oedema in pregnant women. Anaesthesia. 2012 Jun;67(6):646-59. doi: 10.1111/j.1365-2044.2012.07055.x. Epub 2012 Mar 15.
PMID: 22420683
citation: Aya AG, Vialles N, Ripart J. [Anesthesia and preeclampsia]. Ann Fr Anesth Reanim. 2010 May;29(5):e141-7. doi: 10.1016/j.annfar.2010.03.014. Epub 2010 May 15. French.
PMID: 20478690
citation: Urbschat A, Obermuller N, Haferkamp A. Biomarkers of kidney injury. Biomarkers. 2011 Jul;16 Suppl 1:S22-30. doi: 10.3109/1354750X.2011.587129.
PMID: 21707441
citation: Vikse BE, Irgens LM, Leivestad T, Skjaerven R, Iversen BM. Preeclampsia and the risk of end-stage renal disease. N Engl J Med. 2008 Aug 21;359(8):800-9. doi: 10.1056/NEJMoa0706790.
PMID: 18716297
citation: Xin C, Yulong X, Yu C, Changchun C, Feng Z, Xinwei M. Urine neutrophil gelatinase-associated lipocalin and interleukin-18 predict acute kidney injury after cardiac surgery. Ren Fail. 2008;30(9):904-13. doi: 10.1080/08860220802359089.
PMID: 18925531
citation: Martensson J, Martling CR, Oldner A, Bell M. Impact of sepsis on levels of plasma cystatin C in AKI and non-AKI patients. Nephrol Dial Transplant. 2012 Feb;27(2):576-81. doi: 10.1093/ndt/gfr358. Epub 2011 Sep 12.
PMID: 21765189
citation: Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A; Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31. doi: 10.1186/cc5713.
PMID: 17331245
responsible party type: Sponsor
mesh term: Eclampsia
mesh term: Pre-Eclampsia
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 