<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/NCT02210260</url>
  </required_header>
  <id_info>
    <org_study_id>SNE 2190</org_study_id>
    <nct_id>NCT02210260</nct_id>
  </id_info>
  <brief_title>Pain Relief After Colorectal Surgery: Spinal Combined With Painbuster® vs Painbuster® Alone.</brief_title>
  <acronym>PROSP</acronym>
  <official_title>Pain Relief After Colorectal Surgery: Single-shot Spinal Combined With Painbuster® vs Painbuster® Alone. A Pilot Randomised Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>York Teaching Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>York Teaching Hospitals NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Limiting surgical stress and managing postoperative pain are well understood to influence&#xD;
      recovery and outcome from major surgery for colorectal cancer and both are fundamental&#xD;
      aspects of enhanced recovery protocols.&#xD;
&#xD;
      Traditional approaches for dealing with these problems such as epidural or patient controlled&#xD;
      intravenous opioid analgesia are associated with problems that may be detrimental to&#xD;
      postoperative recovery and surgical outcome. As a result there is evidence in the literature&#xD;
      of increasing interest in alternative techniques such as intrathecal anaesthesia or&#xD;
      continuous wound infusion of local anaesthetic, however nobody has examined the effect of&#xD;
      combining the techniques or their impact on the surgical stress response.&#xD;
&#xD;
      We intend to compare patients undergoing major resections for colorectal cancer receiving&#xD;
      intrathecal anaesthesia in combination with a wound infusion of local anaesthetic with those&#xD;
      receiving a continuous wound infusion alone. We will examine the surgical stress response and&#xD;
      postoperative pain control in addition to objective measures of postoperative recovery.&#xD;
&#xD;
      We suggest that our approach will attenuate the surgical stress response and provide optimal&#xD;
      pain control that will ultimately translate in improved recovery and outcome following&#xD;
      surgery for colorectal cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a pilot randomised controlled trial&#xD;
&#xD;
      Hypotheses -&#xD;
&#xD;
      Following colorectal surgery, spinal anaesthesia combined with a continuous infusion of local&#xD;
      anaesthetic into the surgical wound provides&#xD;
&#xD;
        1. better pain relief&#xD;
&#xD;
        2. a reduced stress response&#xD;
&#xD;
      when compared to the use of continuous infusion of local anaesthetic into the surgical wound&#xD;
      alone.&#xD;
&#xD;
      Patients undergoing surgical resection for colorectal cancer will be randomised to receive&#xD;
      either&#xD;
&#xD;
        1. A single shot of spinal anaesthesia plus a continuous infusion of local anaesthetic into&#xD;
           the surgical wound or&#xD;
&#xD;
        2. Continuous infusion of local anaesthetic into the surgical wound&#xD;
&#xD;
      Spinal Anaesthesia&#xD;
&#xD;
      The spinal anaesthetic (SA) with be placed after commencement of general anaesthesia this&#xD;
      will ensure the patients remain blinded to the intervention. SA will be performed in the&#xD;
      lateral position using a midline approach. L3/4 interspace will be identified using Tuffier's&#xD;
      as the anatomical landmark. After confirmation of correct placement using a 25G Whitacre&#xD;
      needle, 12.5 mg of hyperbaric Bupivacaine in a mixture with 500mcg Diamorphine will be&#xD;
      injected intrathecally.&#xD;
&#xD;
      Infusion of local anaesthetic&#xD;
&#xD;
      The catheter through which the infusion of local anaesthetic will be given, will be placed by&#xD;
      the surgeon at the end of the procedure in a location determined by the surgical approach. A&#xD;
      bolus dose of 20ml 0.25% L-Bupivacaine will be injected down the catheters prior to the&#xD;
      connection of the elastomeric pump which will also contain 270ml 0.25% L-Bupivacaine&#xD;
&#xD;
      General anaesthesia will be managed in the same way for both groups&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2013</start_date>
  <completion_date type="Actual">February 2016</completion_date>
  <primary_completion_date type="Actual">February 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Neuroendocrine response to surgery</measure>
    <time_frame>24 hours</time_frame>
    <description>Peripheral blood samples taken at baseline, 60 minutes after surgical incision and 24 hours postoperatively will be analysed for cortisol and noradrenaline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay or fitness for discharge</measure>
    <time_frame>Up to 12 days</time_frame>
    <description>Discharge criteria:&#xD;
Good pain control with oral analgesia.&#xD;
Tolerating solid food without nausea and vomiting.&#xD;
No IV fluid or medication.&#xD;
Independently mobile and self-caring or at the same level as prior to admission.&#xD;
Stable observations and blood biochemistry.&#xD;
No other concerns or complications preventing discharge.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative complications</measure>
    <time_frame>Up to 12 days</time_frame>
    <description>All complications in the postoperative period will be recorded. Particular emphasis will be given to:&#xD;
Wound infection&#xD;
Cardiac failure:&#xD;
Complications related to spinal anaesthesia.&#xD;
Adequacy of deep vein thrombosis prophylaxis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Episodes of hypotension in the postoperative period</measure>
    <time_frame>Up to 12 days</time_frame>
    <description>This will be defined as a sustained systolic blood pressure of less than 90 mm/Hg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative pain</measure>
    <time_frame>Up to 72 hours after surgery</time_frame>
    <description>This will be assessed using a visual analogue scale . Measurements will be taken in recovery then once a day for 72 hours postoperatively. Pain scores will be measured at rest and on coughing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative analgesic requirement</measure>
    <time_frame>Up to 72 hours after surgery</time_frame>
    <description>The total quantity and type (opiate or non-opiate) of all analgesics administered for 72 hours postoperatively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of postoperative IV fluid administered</measure>
    <time_frame>Up to 12 days</time_frame>
    <description>Total amount of IV fluid given in postoperative period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative mobility</measure>
    <time_frame>Up to 12 days</time_frame>
    <description>Postoperative mobility will be assessed as&#xD;
time until able to stand aided and unaided,&#xD;
duration of time spent out of bed on each postoperative day&#xD;
maximum walking distance with assistance on a daily basis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Return of gut function</measure>
    <time_frame>Up to 12 days</time_frame>
    <description>4.2.8 Time to return of gut function This is defined by the oral/enteral tolerance of &gt; 80% of nutritional requirement.&#xD;
These requirements will be assessed individually for each patient in the study by an appropriately trained dietician</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxidative stress</measure>
    <time_frame>For 24 hours</time_frame>
    <description>Peripheral blood samples will be taken at baseline, 60 minutes after surgical incision and 24 hours postoperatively and analysed for heat shock proteins 37 and 32.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory pathway</measure>
    <time_frame>Up to 24 hours after surgery</time_frame>
    <description>Peripheral blood samples taken at baseline, 60 minutes after surgical incision and 24 hours postoperatively will be analysed for IL1.&#xD;
Peritoneal biopsies taken prior to closure of surgical wound and analysed for IL1.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">79</enrollment>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Continuous infusion of local anaesthetic</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Continuous infusion of local anaesthetic into the surgical wound</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Spinal and infusion of local anaesthetic</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A one off spinal anaesthetic plus a continuous infusion of local anaesthetic into the surgical wound</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Spinal and infusion of local anaesthetic</intervention_name>
    <description>Spinal anaesthetic will be performed in the lateral position using a midline approach. L3/4 interspace will be identified using Tuffier's as the anatomical landmark. After confirmation of correct placement using a 25G Whitacre needle, 12.5 mg of hyperbaric Bupivacaine in a mixture with 500mcg Diamorphine will be injected intrathecally.&#xD;
PLUS&#xD;
Painbuster® catheters will be placed by the surgeon at the end of the procedure in a location determined by the surgical approach. A bolus dose of 20ml 0.25% L-Bupivacaine will be injected down the catheters prior to the connection of the elastomeric pump which will also contain 270ml 0.25% L-Bupivacaine.</description>
    <arm_group_label>Spinal and infusion of local anaesthetic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Continuous infusion of local anaesthetic</intervention_name>
    <description>A Painbuster® catheter will be placed by the surgeon at the end of the procedure in a location determined by the surgical approach. A bolus dose of 20ml 0.25% L-Bupivacaine will be injected down the catheters prior to the connection of the elastomeric pump which will also contain 270ml 0.25% L-Bupivacaine.</description>
    <arm_group_label>Continuous infusion of local anaesthetic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bupivacaine</intervention_name>
    <arm_group_label>Continuous infusion of local anaesthetic</arm_group_label>
    <arm_group_label>Spinal and infusion of local anaesthetic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Diamorphine</intervention_name>
    <description>500mcg</description>
    <arm_group_label>Spinal and infusion of local anaesthetic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>A Painbuster® catheter</intervention_name>
    <arm_group_label>Continuous infusion of local anaesthetic</arm_group_label>
    <arm_group_label>Spinal and infusion of local anaesthetic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>25G Whitacre needle</intervention_name>
    <arm_group_label>Spinal and infusion of local anaesthetic</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients who are undergoing either laparoscopic or open colorectal resections will&#xD;
             be considered eligible for the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients under 18 years of age.&#xD;
&#xD;
          -  Pregnant females.&#xD;
&#xD;
          -  Patients undergoing an abdominoperineal resection.&#xD;
&#xD;
          -  Patients who will not contemplate being randomized to receive a spinal anaesthetic.&#xD;
&#xD;
          -  Patients with a history of failure to place an epidural / spinal anaesthetic.&#xD;
&#xD;
          -  Hypersensitivity to local anaesthetics.&#xD;
&#xD;
          -  Lack of capacity to give consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel Harper, MBChB, FRCA</last_name>
    <role>Principal Investigator</role>
    <affiliation>York Teaching Hospital NHS Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Scarborough General Hospital</name>
      <address>
        <city>Scarborough</city>
        <state>North Yorkshire</state>
        <zip>YO12 6QL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>August 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 6, 2014</study_first_posted>
  <last_update_submitted>September 13, 2016</last_update_submitted>
  <last_update_submitted_qc>September 13, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 14, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cancer</keyword>
  <keyword>Colorectal</keyword>
  <keyword>Pain relief</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heroin</mesh_term>
    <mesh_term>Bupivacaine</mesh_term>
    <mesh_term>Anesthetics, Local</mesh_term>
    <mesh_term>Anesthetics</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/NCT02210260
org study id: SNE 2190
nct id: NCT02210260
lead sponsor: 
has dmc: No
Limiting surgical stress and managing postoperative pain are well understood to influence
      recovery and outcome from major surgery for colorectal cancer and both are fundamental
      aspects of enhanced recovery protocols.

      Traditional approaches for dealing with these problems such as epidural or patient controlled
      intravenous opioid analgesia are associated with problems that may be detrimental to
      postoperative recovery and surgical outcome. As a result there is evidence in the literature
      of increasing interest in alternative techniques such as intrathecal anaesthesia or
      continuous wound infusion of local anaesthetic, however nobody has examined the effect of
      combining the techniques or their impact on the surgical stress response.

      We intend to compare patients undergoing major resections for colorectal cancer receiving
      intrathecal anaesthesia in combination with a wound infusion of local anaesthetic with those
      receiving a continuous wound infusion alone. We will examine the surgical stress response and
      postoperative pain control in addition to objective measures of postoperative recovery.

      We suggest that our approach will attenuate the surgical stress response and provide optimal
      pain control that will ultimately translate in improved recovery and outcome following
      surgery for colorectal cancer.
This is a pilot randomised controlled trial

      Hypotheses -

      Following colorectal surgery, spinal anaesthesia combined with a continuous infusion of local
      anaesthetic into the surgical wound provides

        1. better pain relief

        2. a reduced stress response

      when compared to the use of continuous infusion of local anaesthetic into the surgical wound
      alone.

      Patients undergoing surgical resection for colorectal cancer will be randomised to receive
      either

        1. A single shot of spinal anaesthesia plus a continuous infusion of local anaesthetic into
           the surgical wound or

        2. Continuous infusion of local anaesthetic into the surgical wound

      Spinal Anaesthesia

      The spinal anaesthetic (SA) with be placed after commencement of general anaesthesia this
      will ensure the patients remain blinded to the intervention. SA will be performed in the
      lateral position using a midline approach. L3/4 interspace will be identified using Tuffier's
      as the anatomical landmark. After confirmation of correct placement using a 25G Whitacre
      needle, 12.5 mg of hyperbaric Bupivacaine in a mixture with 500mcg Diamorphine will be
      injected intrathecally.

      Infusion of local anaesthetic

      The catheter through which the infusion of local anaesthetic will be given, will be placed by
      the surgeon at the end of the procedure in a location determined by the surgical approach. A
      bolus dose of 20ml 0.25% L-Bupivacaine will be injected down the catheters prior to the
      connection of the elastomeric pump which will also contain 270ml 0.25% L-Bupivacaine

      General anaesthesia will be managed in the same way for both groups
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Neuroendocrine response to surgery
time frame: 24 hours
description: Peripheral blood samples taken at baseline, 60 minutes after surgical incision and 24 hours postoperatively will be analysed for cortisol and noradrenaline.
measure: Length of hospital stay or fitness for discharge
time frame: Up to 12 days
description: Discharge criteria:
Good pain control with oral analgesia.
Tolerating solid food without nausea and vomiting.
No IV fluid or medication.
Independently mobile and self-caring or at the same level as prior to admission.
Stable observations and blood biochemistry.
No other concerns or complications preventing discharge.
measure: Postoperative complications
time frame: Up to 12 days
description: All complications in the postoperative period will be recorded. Particular emphasis will be given to:
Wound infection
Cardiac failure:
Complications related to spinal anaesthesia.
Adequacy of deep vein thrombosis prophylaxis.
measure: Episodes of hypotension in the postoperative period
time frame: Up to 12 days
description: This will be defined as a sustained systolic blood pressure of less than 90 mm/Hg.
measure: Postoperative pain
time frame: Up to 72 hours after surgery
description: This will be assessed using a visual analogue scale . Measurements will be taken in recovery then once a day for 72 hours postoperatively. Pain scores will be measured at rest and on coughing.
measure: Postoperative analgesic requirement
time frame: Up to 72 hours after surgery
description: The total quantity and type (opiate or non-opiate) of all analgesics administered for 72 hours postoperatively.
measure: Amount of postoperative IV fluid administered
time frame: Up to 12 days
description: Total amount of IV fluid given in postoperative period
measure: Postoperative mobility
time frame: Up to 12 days
description: Postoperative mobility will be assessed as
time until able to stand aided and unaided,
duration of time spent out of bed on each postoperative day
maximum walking distance with assistance on a daily basis.
measure: Return of gut function
time frame: Up to 12 days
description: 4.2.8 Time to return of gut function This is defined by the oral/enteral tolerance of > 80% of nutritional requirement.
These requirements will be assessed individually for each patient in the study by an appropriately trained dietician
measure: Oxidative stress
time frame: For 24 hours
description: Peripheral blood samples will be taken at baseline, 60 minutes after surgical incision and 24 hours postoperatively and analysed for heat shock proteins 37 and 32.
measure: Inflammatory pathway
time frame: Up to 24 hours after surgery
description: Peripheral blood samples taken at baseline, 60 minutes after surgical incision and 24 hours postoperatively will be analysed for IL1.
Peritoneal biopsies taken prior to closure of surgical wound and analysed for IL1.
arm group label: Continuous infusion of local anaesthetic
arm group type: Active Comparator
description: Continuous infusion of local anaesthetic into the surgical wound
arm group label: Spinal and infusion of local anaesthetic
arm group type: Experimental
description: A one off spinal anaesthetic plus a continuous infusion of local anaesthetic into the surgical wound
intervention type: Procedure
intervention name: Spinal and infusion of local anaesthetic
description: Spinal anaesthetic will be performed in the lateral position using a midline approach. L3/4 interspace will be identified using Tuffier's as the anatomical landmark. After confirmation of correct placement using a 25G Whitacre needle, 12.5 mg of hyperbaric Bupivacaine in a mixture with 500mcg Diamorphine will be injected intrathecally.
PLUS
Painbuster® catheters will be placed by the surgeon at the end of the procedure in a location determined by the surgical approach. A bolus dose of 20ml 0.25% L-Bupivacaine will be injected down the catheters prior to the connection of the elastomeric pump which will also contain 270ml 0.25% L-Bupivacaine.
arm group label: Spinal and infusion of local anaesthetic
intervention type: Procedure
intervention name: Continuous infusion of local anaesthetic
description: A Painbuster® catheter will be placed by the surgeon at the end of the procedure in a location determined by the surgical approach. A bolus dose of 20ml 0.25% L-Bupivacaine will be injected down the catheters prior to the connection of the elastomeric pump which will also contain 270ml 0.25% L-Bupivacaine.
arm group label: Continuous infusion of local anaesthetic
intervention type: Drug
intervention name: Bupivacaine
arm group label: Continuous infusion of local anaesthetic
arm group label: Spinal and infusion of local anaesthetic
intervention type: Drug
intervention name: Diamorphine
description: 500mcg
arm group label: Spinal and infusion of local anaesthetic
intervention type: Device
intervention name: A Painbuster® catheter
arm group label: Continuous infusion of local anaesthetic
arm group label: Spinal and infusion of local anaesthetic
intervention type: Device
intervention name: 25G Whitacre needle
arm group label: Spinal and infusion of local anaesthetic
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Daniel Harper, MBChB, FRCA
role: Principal Investigator
affiliation: York Teaching Hospital NHS Foundation Trust
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Heroin
mesh term: Bupivacaine
mesh term: Anesthetics, Local
mesh term: Anesthetics