<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/NCT03020641</url>
  </required_header>
  <id_info>
    <org_study_id>A-CGyD-2017</org_study_id>
    <nct_id>NCT03020641</nct_id>
  </id_info>
  <brief_title>Peritoneal Damage in Laparoscopic Surgery</brief_title>
  <official_title>Characterization of Changes in Peritoneal Cells Gene Expression After Standard Versus Low Pressure Laparoscopic Cholecystectomy and Its Clinical Correlation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesized that applying a low intraperitoneal pressure pneumoperitoneum&#xD;
      (≤ 8mmHg) during laparoscopic cholecystectomy, the adverse impact on the surgical peritoneal&#xD;
      environment (measured as gene expression of extracellular matrix, adhesion and inflammatory&#xD;
      cytokine as well as oxidative stress response and apoptotic index), can be minimized and&#xD;
      probably clinical outcomes might be better.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cholelithiasis is one of the most frequent abdominal diseases requiring surgical treatment.&#xD;
      Laparoscopic cholecystectomy is currently the procedure of choice to remove the gallbladder.&#xD;
      There is growing evidence that increased intra-abdominal pressure pneumoperitoneum, even for&#xD;
      short periods of time, is associated with both transient and sometimes persistent adverse&#xD;
      effects that might negatively affect the surgical peritoneal environment .There are some&#xD;
      studies that have demonstrated that using low intraperitoneal pressure pneumoperitoneum,&#xD;
      undesired effects like adverse impact on peritoneal tissue and negative clinical outcomes&#xD;
      could be reduced.Therefore intraperitoneal pressure target during laparoscopy should be the&#xD;
      lowest to allow surgery be securely performed. Many strategies have been tested in order to&#xD;
      improve the volume of gas can be insufflated inside the abdominal cavity while maintaining&#xD;
      low pneumoperitoneum pressure during laparoscopy.So far the most studied strategy has been&#xD;
      deep neuromuscular blockade.However the effect of the depth of neuromuscular blockade in the&#xD;
      intraabdominal volume is still controversial as sometimes in humans its benefits are&#xD;
      marginal.There is scarce information in the medical literature regarding the adverse impact&#xD;
      on peritoneal tissue of high pneumoperitoneum pressure during laparoscopy in humans. In&#xD;
      addition available data are provided by non-prospective, non-randomized and small sample&#xD;
      studies, so randomized controlled trials are required to ascertain this issues.To our&#xD;
      knowledge our study is the first prospective and randomized controlled trial in humans aiming&#xD;
      to study the adverse impact of high pressure pneumoperitoneum on peritoneal tissue as well as&#xD;
      to associate it with clinical outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 27, 2017</start_date>
  <completion_date type="Actual">April 28, 2019</completion_date>
  <primary_completion_date type="Actual">April 28, 2019</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>Other</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Inflammatory Peritoneal Markers</measure>
    <time_frame>he values will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1).</time_frame>
    <description>logaritmic levels of mRNA of the different markers at time 1 hour after creation of the pneumoperitoneum</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of)</measure>
    <time_frame>The values will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1).</time_frame>
    <description>f. CTGF &quot;connective tissue growth factor&quot;. g. MMP-9 &quot;matrix metalloproteinase-9&quot;. h. PAI-I &quot;plasminogen activator inhibitor-I&quot;. i. E-selectin. Samples will be processed to obtain total RNA with TRI Reagent™ (Sigma) and will be quantified with NanoDrop spectrophotometer.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Oxidative Stress Response Marker:MDA (Malondialdehyde)</measure>
    <time_frame>The values of the main variables will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1)</time_frame>
    <description>MDA (malondialdehyde) determination will be done with ELISA</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apoptotic Index</measure>
    <time_frame>The values of the main variables will be obtained from the study of peritoneal tissue samples, one hour after the creation of the pneumoperitoneum compared to basal peritoneal tissue samples.</time_frame>
    <description>This measure is reported as the mean of the difference of the percentage of apoptotic cells at baseline minus the final</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Peritoneal Damage</condition>
  <arm_group>
    <arm_group_label>Low pneumoperitoneum pressure.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pneumoperitoneum pressure at 8 mmHg or lower.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>standard pneumoperitoneum pressure</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pneumoperitoneum pressure at 12 mmHG or higher</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Low pressure pneumoperitoneum</intervention_name>
    <description>Low pressure pneumoperitoneum</description>
    <arm_group_label>Low pneumoperitoneum pressure.</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>standard pneumoperitoneum pressure</intervention_name>
    <description>standard pneumoperitoneum pressure</description>
    <arm_group_label>standard pneumoperitoneum pressure</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients older than 18 years, signed informed consent, undergoing laparoscopic&#xD;
             cholecystectomy for symptomatic cholelithiasis or gallbladder polyps.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Emergency surgery.&#xD;
&#xD;
          -  Previous surgery at supramesocolic compartment.&#xD;
&#xD;
          -  Previous peritoneal inflammatory process.&#xD;
&#xD;
          -  Pregnancy or breastfeeding.&#xD;
&#xD;
          -  Patient refusal to participate in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Ramon y Cajal Hospital</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <results_first_submitted>April 12, 2021</results_first_submitted>
  <results_first_submitted_qc>September 21, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">September 22, 2021</results_first_posted>
  <last_update_submitted>September 21, 2021</last_update_submitted>
  <last_update_submitted_qc>September 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>low pressure pneumoperitoneum</keyword>
  <keyword>standard pressure pneumoperitoneum</keyword>
  <keyword>laparoscopy cholecystectomy</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 27, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/41/NCT03020641/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Data were collected from January 2017 to May 2019</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Control</title>
          <description>Standard pneumoperitoneum pressure (12 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</description>
        </group>
        <group group_id="P2">
          <title>Intervention</title>
          <description>Low pneumoperitoneum pressure (8 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="48"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </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="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Converted to open surgery</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>for surgery not performed</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>5 patients were excluded see Participant flow for more details</population>
      <group_list>
        <group group_id="B1">
          <title>Experimental</title>
          <description>Low pneumoperitoneum pressure (8 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</description>
        </group>
        <group group_id="B2">
          <title>Control</title>
          <description>Standard pneumoperitoneum pressure (12 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</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="47"/>
            <count group_id="B2" value="48"/>
            <count group_id="B3" value="95"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="47"/>
                    <count group_id="B2" value="48"/>
                    <count group_id="B3" value="95"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.47" spread="16.88"/>
                    <measurement group_id="B2" value="51.71" spread="15.72"/>
                    <measurement group_id="B3" value="53.04" spread="16.26"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="47"/>
                    <count group_id="B2" value="48"/>
                    <count group_id="B3" value="95"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="69"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <description>Body mass index</description>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="47"/>
                    <count group_id="B2" value="48"/>
                    <count group_id="B3" value="95"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.63" spread="4.07"/>
                    <measurement group_id="B2" value="27.51" spread="4.6"/>
                    <measurement group_id="B3" value="27.07" spread="4.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ASA</title>
          <description>American Society Anaesthesiologists classification. ASA I A normal healthy patient ASA II A patient with mild systemic disease ASA III A patient with severe systemic disease ASA IV A patient with severe systemic disease that is a constant threat to life ASA V A moribund patient who is not expected to survive without the operation ASA VI A declared brain-dead patient whose organs are being removed for donor purposes</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="47"/>
                    <count group_id="B2" value="48"/>
                    <count group_id="B3" value="95"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>I</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>II</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>III</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>IV</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>Unknow</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_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Inflammatory Peritoneal Markers</title>
        <description>logaritmic levels of mRNA of the different markers at time 1 hour after creation of the pneumoperitoneum</description>
        <time_frame>he values will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1).</time_frame>
        <population>23 excluded samples</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Standard pneumoperitoneum pressure (12 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</description>
          </group>
          <group group_id="O2">
            <title>Experimental</title>
            <description>Low pneumoperitoneum pressure (8 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</description>
          </group>
        </group_list>
        <measure>
          <title>Inflammatory Peritoneal Markers</title>
          <description>logaritmic levels of mRNA of the different markers at time 1 hour after creation of the pneumoperitoneum</description>
          <population>23 excluded samples</population>
          <units>log (pg/ml)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Interleukin 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.80" spread="1.00"/>
                    <measurement group_id="O2" value="1.14" spread="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Interlerukin 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.26" spread="1.34"/>
                    <measurement group_id="O2" value="3.24" spread="1.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Interleukin 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.76" spread="1.01"/>
                    <measurement group_id="O2" value="1.10" spread="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>vascular endotelial growth factor A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.09" spread="0.99"/>
                    <measurement group_id="O2" value="-0.05" spread="0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tumor necrosis factor α</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.71" spread="0.99"/>
                    <measurement group_id="O2" value="-0.74" spread="0.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CXC lingand 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.18" spread="0.99"/>
                    <measurement group_id="O2" value="2.22" spread="0.72"/>
                  </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>
            <groups_desc>Interleukin 1 (IL1)</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>t-test</non_inferiority_desc>
            <p_value>0.058</p_value>
            <p_value_desc>the threshold for statistical significance was p&lt;=0.05.</p_value_desc>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>- 0.34</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.2347</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>- 0.8077</ci_lower_limit>
            <ci_upper_limit>0.1276</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Interleukin 6 (IL6)</non_inferiority_desc>
            <p_value>0.001</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.02</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.29</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.60</ci_lower_limit>
            <ci_upper_limit>-0.44</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Interleukin 10</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.052</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.34</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.211</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.76</ci_lower_limit>
            <ci_upper_limit>0.81</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Vascular Endotelial Grow Factor A</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.815</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.14</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.181</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.50</ci_lower_limit>
            <ci_upper_limit>0.22</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>TNF alfa</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.742</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.03</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.19</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.42</ci_lower_limit>
            <ci_upper_limit>0.36</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Chemokine CXC ligand 2</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.603</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.04</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.2</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.36</ci_lower_limit>
            <ci_upper_limit>0.44</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of)</title>
        <description>f. CTGF &quot;connective tissue growth factor&quot;. g. MMP-9 &quot;matrix metalloproteinase-9&quot;. h. PAI-I &quot;plasminogen activator inhibitor-I&quot;. i. E-selectin. Samples will be processed to obtain total RNA with TRI Reagent™ (Sigma) and will be quantified with NanoDrop spectrophotometer.</description>
        <time_frame>The values will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1).</time_frame>
        <population>13 samples excluded</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Low pneumoperitoneum pressure (8 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Standard pneumoperitoneum pressure (12 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</description>
          </group>
        </group_list>
        <measure>
          <title>Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of)</title>
          <description>f. CTGF &quot;connective tissue growth factor&quot;. g. MMP-9 &quot;matrix metalloproteinase-9&quot;. h. PAI-I &quot;plasminogen activator inhibitor-I&quot;. i. E-selectin. Samples will be processed to obtain total RNA with TRI Reagent™ (Sigma) and will be quantified with NanoDrop spectrophotometer.</description>
          <population>13 samples excluded</population>
          <units>log (pg/ml)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Connective tissue growth factor</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.89" spread="0.61"/>
                    <measurement group_id="O2" value="0.61" spread="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Matrix metalloproteinasa-9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.56" spread="1.15"/>
                    <measurement group_id="O2" value="0.47" spread="1.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plasminogenin activator inhibitor</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.74" spread="0.89"/>
                    <measurement group_id="O2" value="0.24" spread="1.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>E- selectin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.66" spread="139"/>
                    <measurement group_id="O2" value="0.57" spread="1.77"/>
                  </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>
            <groups_desc>Matrix metalloproteinase-9</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.600</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.09</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.28</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.47</ci_lower_limit>
            <ci_upper_limit>0.65</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Plasminogen activator inhibitor-1</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.028</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.50</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>.24</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.030</ci_lower_limit>
            <ci_upper_limit>0.97</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>E-selectin</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.807</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.09</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.64</ci_lower_limit>
            <ci_upper_limit>0.82</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Oxidative Stress Response Marker:MDA (Malondialdehyde)</title>
        <description>MDA (malondialdehyde) determination will be done with ELISA</description>
        <time_frame>The values of the main variables will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1)</time_frame>
        <population>It was impossible to measure MDA due to laboratory problems.</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental</title>
            <description>Low pneumoperitoneum pressure (8 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Standard pneumoperitoneum pressure (12 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</description>
          </group>
        </group_list>
        <measure>
          <title>Oxidative Stress Response Marker:MDA (Malondialdehyde)</title>
          <description>MDA (malondialdehyde) determination will be done with ELISA</description>
          <population>It was impossible to measure MDA due to laboratory problems.</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>Primary</type>
        <title>Apoptotic Index</title>
        <description>This measure is reported as the mean of the difference of the percentage of apoptotic cells at baseline minus the final</description>
        <time_frame>The values of the main variables will be obtained from the study of peritoneal tissue samples, one hour after the creation of the pneumoperitoneum compared to basal peritoneal tissue samples.</time_frame>
        <population>13 samples excluded</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Standard pneumoperitoneum pressure (12 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</description>
          </group>
          <group group_id="O2">
            <title>Experimental</title>
            <description>Low pneumoperitoneum pressure (8 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</description>
          </group>
        </group_list>
        <measure>
          <title>Apoptotic Index</title>
          <description>This measure is reported as the mean of the difference of the percentage of apoptotic cells at baseline minus the final</description>
          <population>13 samples excluded</population>
          <units>difference of the percentage</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.92" spread="24.3"/>
                    <measurement group_id="O2" value="-0.56" spread="12.3"/>
                  </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>Other</non_inferiority_type>
            <p_value>0.862</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.37</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>4.44</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.49</ci_lower_limit>
            <ci_upper_limit>10.21</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>no adverse event data. All-Cause Mortality, Serious, and Other [Not Including Serious] Adverse Events were not monitored/assessed.&quot;</time_frame>
      <desc>All-Cause Mortality, Serious, and Other [Not Including Serious] Adverse Events were not monitored/assessed.&quot;</desc>
      <group_list>
        <group group_id="E1">
          <title>Control</title>
          <description>Standard pneumoperitoneum pressure (12 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</description>
        </group>
        <group group_id="E2">
          <title>Experimental</title>
          <description>Low pneumoperitoneum pressure (8 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage</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="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </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="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </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>
    <limitations_and_caveats>no limitations</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Characterization of changes in peritoneal cells gene expression after standard versus low pressure l</name_or_title>
      <organization>Ramon y Cajal University Hospital</organization>
      <phone>610 312962 ext +34</phone>
      <email>aserranor@salud.madrid.org</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/NCT03020641
org study id: A-CGyD-2017
nct id: NCT03020641
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The investigators hypothesized that applying a low intraperitoneal pressure pneumoperitoneum
      (≤ 8mmHg) during laparoscopic cholecystectomy, the adverse impact on the surgical peritoneal
      environment (measured as gene expression of extracellular matrix, adhesion and inflammatory
      cytokine as well as oxidative stress response and apoptotic index), can be minimized and
      probably clinical outcomes might be better.
Cholelithiasis is one of the most frequent abdominal diseases requiring surgical treatment.
      Laparoscopic cholecystectomy is currently the procedure of choice to remove the gallbladder.
      There is growing evidence that increased intra-abdominal pressure pneumoperitoneum, even for
      short periods of time, is associated with both transient and sometimes persistent adverse
      effects that might negatively affect the surgical peritoneal environment .There are some
      studies that have demonstrated that using low intraperitoneal pressure pneumoperitoneum,
      undesired effects like adverse impact on peritoneal tissue and negative clinical outcomes
      could be reduced.Therefore intraperitoneal pressure target during laparoscopy should be the
      lowest to allow surgery be securely performed. Many strategies have been tested in order to
      improve the volume of gas can be insufflated inside the abdominal cavity while maintaining
      low pneumoperitoneum pressure during laparoscopy.So far the most studied strategy has been
      deep neuromuscular blockade.However the effect of the depth of neuromuscular blockade in the
      intraabdominal volume is still controversial as sometimes in humans its benefits are
      marginal.There is scarce information in the medical literature regarding the adverse impact
      on peritoneal tissue of high pneumoperitoneum pressure during laparoscopy in humans. In
      addition available data are provided by non-prospective, non-randomized and small sample
      studies, so randomized controlled trials are required to ascertain this issues.To our
      knowledge our study is the first prospective and randomized controlled trial in humans aiming
      to study the adverse impact of high pressure pneumoperitoneum on peritoneal tissue as well as
      to associate it with clinical outcomes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Triple (Participant, Care Provider, Investigator)
measure: Inflammatory Peritoneal Markers
time frame: he values will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1).
description: logaritmic levels of mRNA of the different markers at time 1 hour after creation of the pneumoperitoneum
measure: Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of)
time frame: The values will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1).
description: f. CTGF "connective tissue growth factor". g. MMP-9 "matrix metalloproteinase-9". h. PAI-I "plasminogen activator inhibitor-I". i. E-selectin. Samples will be processed to obtain total RNA with TRI Reagent™ (Sigma) and will be quantified with NanoDrop spectrophotometer.
measure: Oxidative Stress Response Marker:MDA (Malondialdehyde)
time frame: The values of the main variables will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1)
description: MDA (malondialdehyde) determination will be done with ELISA
measure: Apoptotic Index
time frame: The values of the main variables will be obtained from the study of peritoneal tissue samples, one hour after the creation of the pneumoperitoneum compared to basal peritoneal tissue samples.
description: This measure is reported as the mean of the difference of the percentage of apoptotic cells at baseline minus the final
arm group label: Low pneumoperitoneum pressure.
arm group type: Experimental
description: Pneumoperitoneum pressure at 8 mmHg or lower.
arm group label: standard pneumoperitoneum pressure
arm group type: Active Comparator
description: Pneumoperitoneum pressure at 12 mmHG or higher
intervention type: Procedure
intervention name: Low pressure pneumoperitoneum
description: Low pressure pneumoperitoneum
arm group label: Low pneumoperitoneum pressure.
intervention type: Procedure
intervention name: standard pneumoperitoneum pressure
description: standard pneumoperitoneum pressure
arm group label: standard pneumoperitoneum pressure
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Spain
responsible party type: Sponsor
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: no limitations
point of contact: 