<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/NCT04503720</url>
  </required_header>
  <id_info>
    <org_study_id>Juronghealth</org_study_id>
    <nct_id>NCT04503720</nct_id>
  </id_info>
  <brief_title>CLoWI Versus PCA Morphine for Pain Control After Major Abdominal Surgery</brief_title>
  <acronym>CLoWI</acronym>
  <official_title>Continuous Local Anaesthetic Wound Infusion (CLoWI) Versus PCA Morphine for Pain Control After Major Abdominal Surgery:A Double Blinded, Randomized, Controlled, Non Inferiority Trial (CLoWI Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>JurongHealth</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>JurongHealth</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>
      Major abdominal surgery is associated with significant complications which may lead to&#xD;
      morbidity and mortality. Pain experienced after surgery affects the recovery from surgery.&#xD;
&#xD;
      Our study aims to evaluate the current gold standard of PCA morphine infusion against a&#xD;
      continuous wound infusion (CLoWI). The use of CLoWI negates the side-effects of opioids, and&#xD;
      will be the first randomised controlled trial to compare PCA (Morphine) with CLoWI-LA&#xD;
      (Ropivacaine).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Major intra-abdominal surgery represents one of the commonest groups of surgical procedures&#xD;
      performed both worldwide and within Singapore. Common general surgical conditions requiring&#xD;
      major intra-abdominal surgery include intestinal pathologies such as cancer, ischaemia,&#xD;
      infection, haemorrhage and perforation.&#xD;
&#xD;
      Major surgery within the abdominal cavity is associated with significant complications which&#xD;
      may be life threatening with an associated hospital mortality rate of as high as 20% for&#xD;
      emergency surgery. Importantly, the recovery from this type of major surgery often entails&#xD;
      significant pain and discomfort for the patient during healing of the abdominal wound and&#xD;
      internal organs from tissue trauma associated with these surgical procedures.&#xD;
&#xD;
      Recent developments in major intra-abdominal surgery have demonstrated the importance of the&#xD;
      early surgical recovery period where common postoperative complications including pain, chest&#xD;
      infection, intestinal ileus and delerium are not only associated with prolonged hospital stay&#xD;
      but are harbingers of poor long term surgical outcomes. Current recommendations for&#xD;
      perioperative management of patients undergoing major intra-abdominal surgery stress the&#xD;
      importance of high quality perioperative care to minimise these sequelae. Key features of&#xD;
      these recommendations are to provide a pain free postoperative surgical recovery with minimal&#xD;
      nausea and vomiting to facilitate early mobilisation and functional recovery from surgery.&#xD;
&#xD;
      Patient controlled analgesia (PCA) with opioids is the first line analgesia therapy currently&#xD;
      used in the immediate post-operative period following major abdominal surgery. PCA with&#xD;
      opioids has some inherent disadvantages that include side-effects of opioids such as nausea,&#xD;
      vomiting, prolonged ileus, dizziness, hallucination and respiratory depression with the need&#xD;
      for supplementary oxygen. This is most pertinent in elderly patients who are more prone to&#xD;
      these side-effects in addition to being more likely to have difficulties in understanding how&#xD;
      to use the PCA and so are more vulnerable to inadequate pain control. Consequently, there may&#xD;
      be a delay in resuming mobility and discharge from hospital.&#xD;
&#xD;
      Continuous local wound infusion (CLoWI) with Ropivacaine that is delivered into the&#xD;
      extraperitoneal plane via an ON-Q® (Halyard) infusion pump has been shown to be an effective&#xD;
      analgesia post-operatively. The use of CLoWI negates the side-effects of opioids and&#xD;
      furthermore, the small portable pump allows early ambulation with no requirement for&#xD;
      supplementary oxygen. Previous published research has demonstrated the benefits of continuous&#xD;
      local wound infusion with local anaesthesia in terms of postoperative analgesia and surgical&#xD;
      recovery However, there are no randomized controlled trials comparing PCA versus continuous&#xD;
      local wound infusion alone; this study will be the first randomised controlled trial to&#xD;
      compare PCA (Morphine) with CLoWI-LA (Ropivacaine).&#xD;
&#xD;
      The local anaesthetic drug to be used for the wound infiltration system is Ropivacaine. Its&#xD;
      mechanism of action involves inhibiting sodium influx through sodium-specific ion channels in&#xD;
      the peripheral nerve axonal cell membrane, in particular, the voltage gated sodium channels.&#xD;
      When the influx of sodium is interrupted, an action potential cannot arise and the conduction&#xD;
      of a pain signal is inhibited. The local anaesthetic will be administered via 2 catheters&#xD;
      that will be placed under direct vision by the surgeon at the time of wound closure.&#xD;
&#xD;
      Ropivacaine 0.5% will be infused at a rate of 4mls/hour (2mls/hour in each catheter) for a&#xD;
      total of 4 days. It is currently in clinical use within our hospital as a routine method of&#xD;
      providing postoperative analgesia following major abdominal surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 1, 2017</start_date>
  <completion_date type="Anticipated">June 2022</completion_date>
  <primary_completion_date type="Anticipated">June 2022</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To compare CLoWI and PCA (Morphine) in terms of post operative pain control</measure>
    <time_frame>5 days</time_frame>
    <description>To determine if wither CLoWI or PCA will achieve better post-operative pain control based on a numerical rating score from 0 - 10</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To compare CLoWI and PCA (Morphine) in terms of post operative complication rates associated with opioid usage</measure>
    <time_frame>5 days</time_frame>
    <description>This includes the following complications - urinary retention, time to flatus, time to bowel opening, nausea and vomiting.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare CLoWI and PCA (Morphine) in terms of the length of postoperative hospital stay.</measure>
    <time_frame>from the time of surgery till discharge, an average of 5 days</time_frame>
    <description>This takes into account the length of time the patient spends in the hospital between the two arms.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">140</enrollment>
  <condition>Surgical Wound</condition>
  <condition>Post-Op Complication</condition>
  <condition>Opioid Use</condition>
  <arm_group>
    <arm_group_label>CLoWI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CLoWI (ropivacaine) and PCA (normal saline)&#xD;
The local anaesthetic infusion will be administered via 2 catheters using a ON-Q® (Halyard) delivery system that will be placed under direct vision by the surgeon at the time of wound closure. 40 mls of 0.25% ropivacaine are infiltrated in the preperitoneal plane. 0.5% ropivacaine will be infused at a rate of 4mls/hour (2mls/hour in each catheter).&#xD;
The dosage 40 mls of 0.25% ropivacaine and 0.5% ropivacaine at 4mls/hr (20mg/hr) over 4 days will be less than the recommended toxic dose of 3-4 mg/kg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PCA</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>PCA (Morphine) and CLoWI (normal saline)&#xD;
Morphine will be administered via the standard PCA protocol in accordance to the hospital's Acute Pain Service Programme:&#xD;
Concentration: 1mg/ml&#xD;
Bolus (Loading): 1mg&#xD;
Lockout Interval: 5 minutes&#xD;
Maximum hourly dose of 10mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>CLoWI</intervention_name>
    <description>Patients will receive a continuous wound infusion with ropivacaine and normal saline in the PCA pump.</description>
    <arm_group_label>CLoWI</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>PCA</intervention_name>
    <description>Patients will receive a continuous wound infusion with normal saline and morphine in the PCA pump.</description>
    <arm_group_label>PCA</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Planned for elective or urgent# open abdominal surgery&#xD;
&#xD;
        Abdominal Surgery may include the following procedures:&#xD;
&#xD;
        A) Urgent laparotomy for perforated viscus, intestinal obstruction. B) Elective abdominal&#xD;
        surgery for upper and lower gastrointestinal surgery&#xD;
&#xD;
          -  Ability to provide informed consent. A signed and dated written informed consent prior&#xD;
             to study participation.&#xD;
&#xD;
          -  Age 21 to 80 years for both males and females&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female subject who is pregnant&#xD;
&#xD;
          -  Inability to comply with PCA instructions due to physical disabilities. For example,&#xD;
             visual or hearing impairment, arthritis, peripheral neuropathy.&#xD;
&#xD;
          -  Known allergy to local anaesthetic or opioid drugs (Morphine).&#xD;
&#xD;
          -  Current or recent on opioid therapy. For example due to chronic pain illness, opioid&#xD;
             (or other) drug abuse or recent surgery.&#xD;
&#xD;
          -  Severe comorbid diseases including liver cirrhosis, renal failure requiring dialysis,&#xD;
             Grade 4 NYHA (New Yoke Heart Association) heart failure, respiratory illness requiring&#xD;
             NIV (Non-Invasive Ventilation), etc.&#xD;
&#xD;
          -  Severe associated acute illness American Society of Anesthesiologists (ASA) Grade 4 or&#xD;
             5 where survival following surgery is not expected&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher Keh, FRCS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ng Teng Fong General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>119074</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ng Teng Fong General Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>609606</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <reference>
    <citation>Liang SS, Ying AJ, Affan ET, Kakala BF, Strippoli GF, Bullingham A, Currow H, Dunn DW, Yeh ZY. Continuous local anaesthetic wound infusion for postoperative pain after midline laparotomy for colorectal resection in adults. Cochrane Database Syst Rev. 2019 Oct 19;10(10):CD012310. doi: 10.1002/14651858.CD012310.pub2.</citation>
    <PMID>31627242</PMID>
  </reference>
  <reference>
    <citation>Prochazka V, Svoboda M, Svaton R, Grolich T, Farkasova M, Kala Z. Use of preperitoneal wound catheter for continuous local anaesthesia after laparoscopic colorectal surgery. Rozhl Chir. 2019 Summer;98(9):356-361. doi: 10.33699/PIS.2019.98.9.356-361.</citation>
    <PMID>31698911</PMID>
  </reference>
  <reference>
    <citation>Dalmau A, Fustran N, Camprubi I, Sanzol R, Redondo S, Ramos E, Torras J, Sabate A. Analgesia with continuous wound infusion of local anesthetic versus saline: Double-blind randomized, controlled trial in hepatectomy. Am J Surg. 2018 Jan;215(1):138-143. doi: 10.1016/j.amjsurg.2017.09.007. Epub 2017 Sep 20.</citation>
    <PMID>28958651</PMID>
  </reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>February 26, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>March 30, 2022</last_update_submitted>
  <last_update_submitted_qc>March 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>continuous local wound infusion</keyword>
  <keyword>opioids</keyword>
  <keyword>post-operative pain</keyword>
  <keyword>surgical incision</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Postoperative Complications</mesh_term>
    <mesh_term>Surgical Wound</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04503720
org study id: Juronghealth
nct id: NCT04503720
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Major abdominal surgery is associated with significant complications which may lead to
      morbidity and mortality. Pain experienced after surgery affects the recovery from surgery.

      Our study aims to evaluate the current gold standard of PCA morphine infusion against a
      continuous wound infusion (CLoWI). The use of CLoWI negates the side-effects of opioids, and
      will be the first randomised controlled trial to compare PCA (Morphine) with CLoWI-LA
      (Ropivacaine).
Major intra-abdominal surgery represents one of the commonest groups of surgical procedures
      performed both worldwide and within Singapore. Common general surgical conditions requiring
      major intra-abdominal surgery include intestinal pathologies such as cancer, ischaemia,
      infection, haemorrhage and perforation.

      Major surgery within the abdominal cavity is associated with significant complications which
      may be life threatening with an associated hospital mortality rate of as high as 20% for
      emergency surgery. Importantly, the recovery from this type of major surgery often entails
      significant pain and discomfort for the patient during healing of the abdominal wound and
      internal organs from tissue trauma associated with these surgical procedures.

      Recent developments in major intra-abdominal surgery have demonstrated the importance of the
      early surgical recovery period where common postoperative complications including pain, chest
      infection, intestinal ileus and delerium are not only associated with prolonged hospital stay
      but are harbingers of poor long term surgical outcomes. Current recommendations for
      perioperative management of patients undergoing major intra-abdominal surgery stress the
      importance of high quality perioperative care to minimise these sequelae. Key features of
      these recommendations are to provide a pain free postoperative surgical recovery with minimal
      nausea and vomiting to facilitate early mobilisation and functional recovery from surgery.

      Patient controlled analgesia (PCA) with opioids is the first line analgesia therapy currently
      used in the immediate post-operative period following major abdominal surgery. PCA with
      opioids has some inherent disadvantages that include side-effects of opioids such as nausea,
      vomiting, prolonged ileus, dizziness, hallucination and respiratory depression with the need
      for supplementary oxygen. This is most pertinent in elderly patients who are more prone to
      these side-effects in addition to being more likely to have difficulties in understanding how
      to use the PCA and so are more vulnerable to inadequate pain control. Consequently, there may
      be a delay in resuming mobility and discharge from hospital.

      Continuous local wound infusion (CLoWI) with Ropivacaine that is delivered into the
      extraperitoneal plane via an ON-Q® (Halyard) infusion pump has been shown to be an effective
      analgesia post-operatively. The use of CLoWI negates the side-effects of opioids and
      furthermore, the small portable pump allows early ambulation with no requirement for
      supplementary oxygen. Previous published research has demonstrated the benefits of continuous
      local wound infusion with local anaesthesia in terms of postoperative analgesia and surgical
      recovery However, there are no randomized controlled trials comparing PCA versus continuous
      local wound infusion alone; this study will be the first randomised controlled trial to
      compare PCA (Morphine) with CLoWI-LA (Ropivacaine).

      The local anaesthetic drug to be used for the wound infiltration system is Ropivacaine. Its
      mechanism of action involves inhibiting sodium influx through sodium-specific ion channels in
      the peripheral nerve axonal cell membrane, in particular, the voltage gated sodium channels.
      When the influx of sodium is interrupted, an action potential cannot arise and the conduction
      of a pain signal is inhibited. The local anaesthetic will be administered via 2 catheters
      that will be placed under direct vision by the surgeon at the time of wound closure.

      Ropivacaine 0.5% will be infused at a rate of 4mls/hour (2mls/hour in each catheter) for a
      total of 4 days. It is currently in clinical use within our hospital as a routine method of
      providing postoperative analgesia following major abdominal surgery.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: To compare CLoWI and PCA (Morphine) in terms of post operative pain control
time frame: 5 days
description: To determine if wither CLoWI or PCA will achieve better post-operative pain control based on a numerical rating score from 0 - 10
measure: To compare CLoWI and PCA (Morphine) in terms of post operative complication rates associated with opioid usage
time frame: 5 days
description: This includes the following complications - urinary retention, time to flatus, time to bowel opening, nausea and vomiting.
measure: To compare CLoWI and PCA (Morphine) in terms of the length of postoperative hospital stay.
time frame: from the time of surgery till discharge, an average of 5 days
description: This takes into account the length of time the patient spends in the hospital between the two arms.
arm group label: CLoWI
arm group type: Experimental
description: CLoWI (ropivacaine) and PCA (normal saline)
The local anaesthetic infusion will be administered via 2 catheters using a ON-Q® (Halyard) delivery system that will be placed under direct vision by the surgeon at the time of wound closure. 40 mls of 0.25% ropivacaine are infiltrated in the preperitoneal plane. 0.5% ropivacaine will be infused at a rate of 4mls/hour (2mls/hour in each catheter).
The dosage 40 mls of 0.25% ropivacaine and 0.5% ropivacaine at 4mls/hr (20mg/hr) over 4 days will be less than the recommended toxic dose of 3-4 mg/kg.
arm group label: PCA
arm group type: Active Comparator
description: PCA (Morphine) and CLoWI (normal saline)
Morphine will be administered via the standard PCA protocol in accordance to the hospital's Acute Pain Service Programme:
Concentration: 1mg/ml
Bolus (Loading): 1mg
Lockout Interval: 5 minutes
Maximum hourly dose of 10mg
intervention type: Device
intervention name: CLoWI
description: Patients will receive a continuous wound infusion with ropivacaine and normal saline in the PCA pump.
arm group label: CLoWI
intervention type: Device
intervention name: PCA
description: Patients will receive a continuous wound infusion with normal saline and morphine in the PCA pump.
arm group label: PCA
criteria: 
gender: All
minimum age: 21 Years
maximum age: 80 Years
healthy volunteers: No
last name: Christopher Keh, FRCS
role: Principal Investigator
affiliation: Ng Teng Fong General Hospital
facility: 
facility: 
country: Singapore
citation: Liang SS, Ying AJ, Affan ET, Kakala BF, Strippoli GF, Bullingham A, Currow H, Dunn DW, Yeh ZY. Continuous local anaesthetic wound infusion for postoperative pain after midline laparotomy for colorectal resection in adults. Cochrane Database Syst Rev. 2019 Oct 19;10(10):CD012310. doi: 10.1002/14651858.CD012310.pub2.
PMID: 31627242
citation: Prochazka V, Svoboda M, Svaton R, Grolich T, Farkasova M, Kala Z. Use of preperitoneal wound catheter for continuous local anaesthesia after laparoscopic colorectal surgery. Rozhl Chir. 2019 Summer;98(9):356-361. doi: 10.33699/PIS.2019.98.9.356-361.
PMID: 31698911
citation: Dalmau A, Fustran N, Camprubi I, Sanzol R, Redondo S, Ramos E, Torras J, Sabate A. Analgesia with continuous wound infusion of local anesthetic versus saline: Double-blind randomized, controlled trial in hepatectomy. Am J Surg. 2018 Jan;215(1):138-143. doi: 10.1016/j.amjsurg.2017.09.007. Epub 2017 Sep 20.
PMID: 28958651
responsible party type: Sponsor
mesh term: Postoperative Complications
mesh term: Surgical Wound
sharing ipd: No