<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/NCT02256228</url>
  </required_header>
  <id_info>
    <org_study_id>IPLA-CRS</org_study_id>
    <nct_id>NCT02256228</nct_id>
  </id_info>
  <brief_title>Intra-Peritoneal Local Anaesthesia After Cytoreductive Surgery</brief_title>
  <acronym>IPLA</acronym>
  <official_title>Peroperative Analgesia Following Cytoreductive Surgery. A Randomized, Double-blind, Comparison Between Intra-peritoneal Local Anesthesia and Placebo - Multicenter Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Göteborg University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Göteborg University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Can perioperative administration of intra-peritoneal local anaesthetics further reduce&#xD;
      postoperative pain, inflammation and outcome in patients undergoing major abdominal surgery&#xD;
      (cytoreductive surgery) and managed with thoracic epidural analgesia? - Multicenter study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of this study is to measure the efficacy of local anesthetics (LA) administered into&#xD;
      the intra-peritoneal cavity compared to placebo. Our hypothesis is that the injection of&#xD;
      local LAs intra-peritoneally would reduce post-operative pain and the inflammatory process&#xD;
      caused by the massive release of cytokines during extensive cytoreductive surgery. The study&#xD;
      is a controlled, parallel group, double blind, prospective, randomized and performed at&#xD;
      Sahlgrenska University Hospital in Goteborg, Sweden . Twenty mL of ropivacaine or saline&#xD;
      would be injected every hour by an automatic pump via the intra-peritoneal catheter into the&#xD;
      abdomen according to group randomization in order to double blind patients and all personnel&#xD;
      involved in the study.&#xD;
&#xD;
      The parameters that would be evaluated are inflammatory markers, postoperative morbidity,&#xD;
      pain intensity, consumption of morphine, cognitive function and progression-free survival.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">December 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Inflammatory Markers</measure>
    <time_frame>0-48 hours postoperatively</time_frame>
    <description>Analysis of the following inflammatory markers with Multiplex: IL(interleukin)-1β, IL-1rα, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17A, zBasic FGF (Fibroblast Growth Factor), Eotaxin, G-CSF (granulocyte colony stimulating factor), GM-CSF granulocyte macrophage colony stimulating factor), IFN-γ (interferon), IP-10 (immune protein), MCP-1 (monocyte chemotactic protein), MCAF (monocyte chemotactic and activating factor), MIP-1α (macrophage inflammatory protein), MIP-1β, PDGF-BB (platelet-derived growth factor), RANTES (regulated on activation, normal T cell expressed and secreted), TNF-α (tumor necrosis factor), VEGF (vascular endothelial growth factor)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Postoperative Morphine consumption</measure>
    <time_frame>0-48 hours postoperatively</time_frame>
    <description>Total amount of Morphine consumed during the first 48 hours after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Intensity</measure>
    <time_frame>0-48 hours postoperatively</time_frame>
    <description>Pain Intensity is measured with Numeric Rating Score 0-10</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Function</measure>
    <time_frame>0-1 month postoperatively</time_frame>
    <description>Patients will complete the following neurophysiological tests upon entering the study and within one month after surgery: Verbal Learning Test (VLT), Concept Shifting Test (CST), Letter-Digit Coding, Verbal Learning Test - Delayed Recall (VLT-D)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>0-3 years postoperatively</time_frame>
    <description>Progression-free Survival measures the length of time after treatment during which the cancer being treated does not get worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative Morbidity/Complications</measure>
    <time_frame>0-30 days postoperatively</time_frame>
    <description>Measuring the numbers of Postoperative Morbidity/Complications within one month after surgery:&#xD;
Morbidity:&#xD;
Local infections&#xD;
Urinary infection (urine culture)&#xD;
Pneumonia (X-ray, C-reactive protein, Fever)&#xD;
Sepsis (Fever, Leucocyte count in blood, Heart Rate, Respiratory Rate)&#xD;
Pleural fluid (X-ray verified)&#xD;
Deep Vein Thrombosis (D-dimer, ultrasound verified)&#xD;
Pulmonary embolism (Computed Tomography/ Scint-X)&#xD;
Acute Myocardial Infarction (Electrocardiography, Troponin I)&#xD;
Atrial fibrillation or serious arrhythmia during the first 48 hours after surgery (Electrocardiography)&#xD;
Respiratory failure (prolonged mechanical ventilation)&#xD;
Renal failure (Serum Creatinine, Diuresis, AKIN criteria)&#xD;
Inotropic needs &gt; 12 hours after surgery&#xD;
Surgical Complications:&#xD;
Intraabdominal bleeding&#xD;
Leakage from anastomosis&#xD;
Abdominal abscess&#xD;
Paralytic ileus&#xD;
Pancreatic leakage (requiring drainage)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Group R</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ropivacaine is instillated through one multi-hole catheter wich would be inserted percutaneously in all patients and tunnelled about 1-2 cm lateral to the abdominal incision and the tip of the catheter placed in the intra-peritoneal cavity. The catheter would not be ligated and fixed in situ intra-peritoneally. Twenty ml of Ropivacaine would be injected subcutaneously along both sides of the incision prior to skin closure. Additionally, 20 ml of Ropivacaine (1mg/mL) would be injected every hour by an automatic pump via the intra-peritoneal catheter into the abdomen.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group P</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Saline is instillated through one multi-hole catheter wich would be inserted percutaneously in all patients and tunnelled about 1-2 cm lateral to the abdominal incision and the tip of the catheter placed in the intra-peritoneal cavity. The catheter would not be ligated and fixed in situ intra-peritoneally. Twenty ml of Saline would be injected subcutaneously along both sides of the incision prior to skin closure. Additionally, 20 ml of Saline would be injected every hour by an automatic pump via the intra-peritoneal catheter into the abdomen.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ropivacaine</intervention_name>
    <description>Active Group</description>
    <arm_group_label>Group R</arm_group_label>
    <other_name>Narop</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Placebo Comparator</description>
    <arm_group_label>Group P</arm_group_label>
    <other_name>Sodium Chloride</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Patients with widespread malignant intra-abdominal ovary cancer stadium III-IV and are&#xD;
        operated by extensive resection of intra-abdominal viscera as well as the parietal&#xD;
        peritoneum (cytoreductive surgery, CRS)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Body mass index &gt; 35&#xD;
&#xD;
          -  American Society of Anesthesiologists classification &gt; 3&#xD;
&#xD;
          -  Renal dysfunction&#xD;
&#xD;
          -  Allergic to acetylsalicylic acid&#xD;
&#xD;
          -  Unwilling to provide informed consent&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>74 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sven-Egron Thorn, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dept. of Anesthesia and Intensive Care, Sahlgrenska University Hospital, Goteborg, Sweden</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anil Gupta, MD PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Dept. of Anesthesia and Intensive Care, Orebro University Hospital, Orebro, Sweden</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sven-Erik Ricksten, MD PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Dept. of Anesthesia and Intensive Care, Sahlgrenska University Hospital, Goteborg, Sweden</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dept. of Gynecological Surgery and Anesthesia and Intensive Care, Sahlgrenska University Hospital</name>
      <address>
        <city>Goteborg</city>
        <zip>SE41385</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>October 1, 2014</study_first_submitted>
  <study_first_submitted_qc>October 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2014</study_first_posted>
  <last_update_submitted>January 14, 2019</last_update_submitted>
  <last_update_submitted_qc>January 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Analgesia</keyword>
  <keyword>Local infiltration analgesia</keyword>
  <keyword>Pain, relief</keyword>
  <keyword>Pain, Postoperative</keyword>
  <keyword>Intra-peritoneal analgesia</keyword>
  <keyword>Ropivacaine</keyword>
  <keyword>Saline</keyword>
  <keyword>Therapeutic Uses</keyword>
  <keyword>Analgesics, Non-Narcotic</keyword>
  <keyword>Analgesics</keyword>
  <keyword>Opioids</keyword>
  <keyword>Morphine</keyword>
  <keyword>Pain</keyword>
  <keyword>Postoperative Complications</keyword>
  <keyword>Physiological Effects of Drugs</keyword>
  <keyword>Anesthetics, Local</keyword>
  <keyword>Anesthetic</keyword>
  <keyword>Cytoreductive</keyword>
  <keyword>Surgery</keyword>
  <keyword>Cancer</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ropivacaine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02256228
org study id: IPLA-CRS
nct id: NCT02256228
lead sponsor: 
has dmc: No
Can perioperative administration of intra-peritoneal local anaesthetics further reduce
      postoperative pain, inflammation and outcome in patients undergoing major abdominal surgery
      (cytoreductive surgery) and managed with thoracic epidural analgesia? - Multicenter study.
The aim of this study is to measure the efficacy of local anesthetics (LA) administered into
      the intra-peritoneal cavity compared to placebo. Our hypothesis is that the injection of
      local LAs intra-peritoneally would reduce post-operative pain and the inflammatory process
      caused by the massive release of cytokines during extensive cytoreductive surgery. The study
      is a controlled, parallel group, double blind, prospective, randomized and performed at
      Sahlgrenska University Hospital in Goteborg, Sweden . Twenty mL of ropivacaine or saline
      would be injected every hour by an automatic pump via the intra-peritoneal catheter into the
      abdomen according to group randomization in order to double blind patients and all personnel
      involved in the study.

      The parameters that would be evaluated are inflammatory markers, postoperative morbidity,
      pain intensity, consumption of morphine, cognitive function and progression-free survival.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Inflammatory Markers
time frame: 0-48 hours postoperatively
description: Analysis of the following inflammatory markers with Multiplex: IL(interleukin)-1β, IL-1rα, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17A, zBasic FGF (Fibroblast Growth Factor), Eotaxin, G-CSF (granulocyte colony stimulating factor), GM-CSF granulocyte macrophage colony stimulating factor), IFN-γ (interferon), IP-10 (immune protein), MCP-1 (monocyte chemotactic protein), MCAF (monocyte chemotactic and activating factor), MIP-1α (macrophage inflammatory protein), MIP-1β, PDGF-BB (platelet-derived growth factor), RANTES (regulated on activation, normal T cell expressed and secreted), TNF-α (tumor necrosis factor), VEGF (vascular endothelial growth factor)
measure: Postoperative Morphine consumption
time frame: 0-48 hours postoperatively
description: Total amount of Morphine consumed during the first 48 hours after surgery
measure: Pain Intensity
time frame: 0-48 hours postoperatively
description: Pain Intensity is measured with Numeric Rating Score 0-10
measure: Cognitive Function
time frame: 0-1 month postoperatively
description: Patients will complete the following neurophysiological tests upon entering the study and within one month after surgery: Verbal Learning Test (VLT), Concept Shifting Test (CST), Letter-Digit Coding, Verbal Learning Test - Delayed Recall (VLT-D)
measure: Progression-free Survival
time frame: 0-3 years postoperatively
description: Progression-free Survival measures the length of time after treatment during which the cancer being treated does not get worse.
measure: Postoperative Morbidity/Complications
time frame: 0-30 days postoperatively
description: Measuring the numbers of Postoperative Morbidity/Complications within one month after surgery:
Morbidity:
Local infections
Urinary infection (urine culture)
Pneumonia (X-ray, C-reactive protein, Fever)
Sepsis (Fever, Leucocyte count in blood, Heart Rate, Respiratory Rate)
Pleural fluid (X-ray verified)
Deep Vein Thrombosis (D-dimer, ultrasound verified)
Pulmonary embolism (Computed Tomography/ Scint-X)
Acute Myocardial Infarction (Electrocardiography, Troponin I)
Atrial fibrillation or serious arrhythmia during the first 48 hours after surgery (Electrocardiography)
Respiratory failure (prolonged mechanical ventilation)
Renal failure (Serum Creatinine, Diuresis, AKIN criteria)
Inotropic needs > 12 hours after surgery
Surgical Complications:
Intraabdominal bleeding
Leakage from anastomosis
Abdominal abscess
Paralytic ileus
Pancreatic leakage (requiring drainage)
arm group label: Group R
arm group type: Active Comparator
description: Ropivacaine is instillated through one multi-hole catheter wich would be inserted percutaneously in all patients and tunnelled about 1-2 cm lateral to the abdominal incision and the tip of the catheter placed in the intra-peritoneal cavity. The catheter would not be ligated and fixed in situ intra-peritoneally. Twenty ml of Ropivacaine would be injected subcutaneously along both sides of the incision prior to skin closure. Additionally, 20 ml of Ropivacaine (1mg/mL) would be injected every hour by an automatic pump via the intra-peritoneal catheter into the abdomen.
arm group label: Group P
arm group type: Placebo Comparator
description: Saline is instillated through one multi-hole catheter wich would be inserted percutaneously in all patients and tunnelled about 1-2 cm lateral to the abdominal incision and the tip of the catheter placed in the intra-peritoneal cavity. The catheter would not be ligated and fixed in situ intra-peritoneally. Twenty ml of Saline would be injected subcutaneously along both sides of the incision prior to skin closure. Additionally, 20 ml of Saline would be injected every hour by an automatic pump via the intra-peritoneal catheter into the abdomen.
intervention type: Drug
intervention name: Ropivacaine
description: Active Group
arm group label: Group R
other name: Narop
intervention type: Drug
intervention name: Saline
description: Placebo Comparator
arm group label: Group P
other name: Sodium Chloride
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 74 Years
healthy volunteers: No
last name: Sven-Egron Thorn, MD PhD
role: Principal Investigator
affiliation: Dept. of Anesthesia and Intensive Care, Sahlgrenska University Hospital, Goteborg, Sweden
last name: Anil Gupta, MD PhD
role: Study Chair
affiliation: Dept. of Anesthesia and Intensive Care, Orebro University Hospital, Orebro, Sweden
last name: Sven-Erik Ricksten, MD PhD
role: Study Chair
affiliation: Dept. of Anesthesia and Intensive Care, Sahlgrenska University Hospital, Goteborg, Sweden
facility: 
country: Sweden
responsible party type: Sponsor
mesh term: Ropivacaine