<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/NCT01677143</url>
  </required_header>
  <id_info>
    <org_study_id>SUS2012CMR01</org_study_id>
    <secondary_id>2012-002356-16</secondary_id>
    <nct_id>NCT01677143</nct_id>
  </id_info>
  <brief_title>Pre-emptive Local Anaesthesia in Gynecological Laparoscopy</brief_title>
  <official_title>Pre-emptive Local Anaesthesia in Gynecological Laparoscopy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Helse Stavanger HF</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Helse Stavanger HF</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pre-emptive local anaesthetics are widely used in laparoscopic surgery, but there is no&#xD;
      really consistent evidence that it is useful. Studies in the literature have shown&#xD;
      contradicting results. At our hospital we are currently using pre-emptive local anaesthetics&#xD;
      in the trocar areas, but as the literature does not give a clear and clinically relevant&#xD;
      answer, we need to find out more. This study aims to see if pre-emptive local anaesthetics&#xD;
      are useful in the setting of our day-case, laparoscopic surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study design is prospective, randomized, and double-blinded with parallel assignments. It&#xD;
      will compare pre-emptive incisional injection of bupivacaine, 5 mg/ml, with a placebo&#xD;
      injection (saline). The clinically relevant comparison should probably be between injection&#xD;
      of local anaesthetics and no injection at all. However a study design like that would make&#xD;
      blinding impossible and probably not acceptable as a research design for a study which aims&#xD;
      to be published.&#xD;
&#xD;
      The aim of the study is to test if pre-emptive injection of long-lasting, local anaesthetics&#xD;
      reduces post-operative pain. As local anaesthetics are already implemented in our routine,&#xD;
      the hypothesis is that it has a positive effect by reducing postoperative pain. The null&#xD;
      hypothesis is that there is no difference between local anaesthetics and placebo.&#xD;
&#xD;
      The recruitment of patients will be from our daily surgery, and consecutive patients who are&#xD;
      eligible for day-case, laparoscopic surgery will be asked to participate.&#xD;
&#xD;
      To have a clinically important reduction of post-operative pain a difference of 2 units on a&#xD;
      0-10 numerical rating scale (NRS) is chosen for the sample size calculation. A smaller&#xD;
      difference in pain score is not considered clinically relevant in our opinion. With a power&#xD;
      of at least 80% this gives 20 patients in total, 10 in each arm. The power calculation was&#xD;
      done by statistician S. Johnsen at the University of Surrey. We will include 24 patients&#xD;
      altogether to cover for any losses to follow-up. The drop-out rates in clinical trials are&#xD;
      usually estimated at 20 %, which would give 25 patients to be included (20/ (1-0.2) = 25).&#xD;
      This study has, however, a very short follow-up period, so the drop-out rate is expected to&#xD;
      be smaller. Drop-outs will be recorded and accounted for.&#xD;
&#xD;
      24 participants will be randomized in blocks of 6 patients. Block randomization is chosen to&#xD;
      avoid pooling by chance.&#xD;
&#xD;
      All procedures will be done by one surgeon. This might be a subject for criticism as one can&#xD;
      say that the results in the study are only true for one surgeon in a particular setting. But&#xD;
      the need for standardization is very important in studies like this, as pointed out by&#xD;
      Wilder-Smith (Wilder-Smith, O. H. 2000).&#xD;
&#xD;
      The time of the randomization is identified as the breakage of the study drug vial. If a&#xD;
      potential candidate is found to satisfy any exclusion criteria or withdraws the consent&#xD;
      before the vial is opened, the patient is not randomised. The study ID number and the study&#xD;
      drug vial will be made available for the next potential candidate.&#xD;
&#xD;
      If a potential candidate is excluded for any reason after the breakage of the vial but before&#xD;
      the completion of the injection of the study drug, the study ID number will be coded as&#xD;
      Protocol Violation and excluded from the statistical analyses.&#xD;
&#xD;
      The patient, nursing staff and the surgeon will all be blinded to the substance injected.&#xD;
&#xD;
      Infiltration in the primary, umbilical site will be blind, but as close to the fascia as&#xD;
      possible. The secondary port infiltrations will be done under visual guidance from the&#xD;
      laparoscope, in the fascia and close to the peritoneum. Bupivacaine in a concentration of 5&#xD;
      mg/ml will be used and 5 ml of the solution will be injected at each port site. The patients&#xD;
      who get placebo will get 5 ml of physiologic saline injected at each port site.&#xD;
&#xD;
      The primary outcome of the study will be movement-evoked pain (MEP) 5 hours after surgery, as&#xD;
      half-life of bupivacaine is 4-6 hours. Movement-evoked pain is the most important outcome&#xD;
      measure, because the goal is to get the patient back to normal, daily activities as soon as&#xD;
      possible. Trials measuring both movement evoked pain and pain at rest (PAR) suggests that MEP&#xD;
      is much more intense than PAR postoperative (Srikandarajah et al, 2011). Pain will be&#xD;
      measured on a 10 cm long Numerical Rating Scale (NRS) where 0 cm is no pain and 10 cm is&#xD;
      severe pain. NRS is validated as a good tool for pain measurement at different ages and&#xD;
      education levels (Gagliese et al, 2005).&#xD;
&#xD;
      Secondary outcome measures will be pain at rest at 2 and 5 hours postoperative, and use of&#xD;
      rescue analgesics. Pain at rest must, of course, be recorded before movement evoked pain.&#xD;
&#xD;
      The pain scoring will be done by the patient with help from the nurses at the ward at 2 and 5&#xD;
      hours postoperative, and both will be blinded to which arm the patient is in.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">September 2013</completion_date>
  <primary_completion_date type="Actual">September 2013</primary_completion_date>
  <phase>Phase 4</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>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Postoperative movement-evoked pain</measure>
    <time_frame>5 hours postoperative</time_frame>
    <description>The primary outcome of the study will be movement-evoked pain (MEP) 5 hours after surgery, as half-life of bupivacaine is 4-6 hours. Movement-evoked pain is the most important outcome measure, because the goal is to get the patient back to normal, daily activities as soon as possible.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain at rest</measure>
    <time_frame>2 and 5 hours postoperative</time_frame>
    <description>Secondary outcome measures will be pain at rest at 2 and 5 hours postoperative.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rescue analgetics</measure>
    <time_frame>5 hours postoperative</time_frame>
    <description>Use of rescue analgesics postoperative.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Pain, Postoperative</condition>
  <arm_group>
    <arm_group_label>bupivacaine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Injection of 5 ml bupivacaine, 5mg/ml in each port site.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Injection of 5 ml saline in each port site.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bupivacaine 5mg/ml</intervention_name>
    <description>5 ml in trocar area</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>bupivacaine</arm_group_label>
    <other_name>Marcain</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women ≥18 years of age&#xD;
&#xD;
          -  Planned day-case laparoscopic surgery&#xD;
&#xD;
          -  Signed Written Informed Consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ASA score 3-6&#xD;
&#xD;
          -  Chronic pain/ Regular use of analgesics&#xD;
&#xD;
          -  Inability to understand Norwegian language&#xD;
&#xD;
          -  Drug or alcohol abuse&#xD;
&#xD;
          -  Inability to understand or sign the Written Informed Consent form&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Caroline Ravndal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Helse Stavanger HF</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stavanger University Hospital</name>
      <address>
        <city>Stavanger</city>
        <zip>4068</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>August 24, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 31, 2012</study_first_posted>
  <last_update_submitted>April 25, 2016</last_update_submitted>
  <last_update_submitted_qc>April 25, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 26, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Local anesthetic</keyword>
  <keyword>Preemptive analgesia</keyword>
  <keyword>Postoperative pain</keyword>
  <keyword>Laparoscopy</keyword>
  <keyword>Gynecological surgery</keyword>
  <keyword>Day-case surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bupivacaine</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/NCT01677143
org study id: SUS2012CMR01
secondary id: 2012-002356-16
nct id: NCT01677143
lead sponsor: 
has dmc: No
Pre-emptive local anaesthetics are widely used in laparoscopic surgery, but there is no
      really consistent evidence that it is useful. Studies in the literature have shown
      contradicting results. At our hospital we are currently using pre-emptive local anaesthetics
      in the trocar areas, but as the literature does not give a clear and clinically relevant
      answer, we need to find out more. This study aims to see if pre-emptive local anaesthetics
      are useful in the setting of our day-case, laparoscopic surgery.
The study design is prospective, randomized, and double-blinded with parallel assignments. It
      will compare pre-emptive incisional injection of bupivacaine, 5 mg/ml, with a placebo
      injection (saline). The clinically relevant comparison should probably be between injection
      of local anaesthetics and no injection at all. However a study design like that would make
      blinding impossible and probably not acceptable as a research design for a study which aims
      to be published.

      The aim of the study is to test if pre-emptive injection of long-lasting, local anaesthetics
      reduces post-operative pain. As local anaesthetics are already implemented in our routine,
      the hypothesis is that it has a positive effect by reducing postoperative pain. The null
      hypothesis is that there is no difference between local anaesthetics and placebo.

      The recruitment of patients will be from our daily surgery, and consecutive patients who are
      eligible for day-case, laparoscopic surgery will be asked to participate.

      To have a clinically important reduction of post-operative pain a difference of 2 units on a
      0-10 numerical rating scale (NRS) is chosen for the sample size calculation. A smaller
      difference in pain score is not considered clinically relevant in our opinion. With a power
      of at least 80% this gives 20 patients in total, 10 in each arm. The power calculation was
      done by statistician S. Johnsen at the University of Surrey. We will include 24 patients
      altogether to cover for any losses to follow-up. The drop-out rates in clinical trials are
      usually estimated at 20 %, which would give 25 patients to be included (20/ (1-0.2) = 25).
      This study has, however, a very short follow-up period, so the drop-out rate is expected to
      be smaller. Drop-outs will be recorded and accounted for.

      24 participants will be randomized in blocks of 6 patients. Block randomization is chosen to
      avoid pooling by chance.

      All procedures will be done by one surgeon. This might be a subject for criticism as one can
      say that the results in the study are only true for one surgeon in a particular setting. But
      the need for standardization is very important in studies like this, as pointed out by
      Wilder-Smith (Wilder-Smith, O. H. 2000).

      The time of the randomization is identified as the breakage of the study drug vial. If a
      potential candidate is found to satisfy any exclusion criteria or withdraws the consent
      before the vial is opened, the patient is not randomised. The study ID number and the study
      drug vial will be made available for the next potential candidate.

      If a potential candidate is excluded for any reason after the breakage of the vial but before
      the completion of the injection of the study drug, the study ID number will be coded as
      Protocol Violation and excluded from the statistical analyses.

      The patient, nursing staff and the surgeon will all be blinded to the substance injected.

      Infiltration in the primary, umbilical site will be blind, but as close to the fascia as
      possible. The secondary port infiltrations will be done under visual guidance from the
      laparoscope, in the fascia and close to the peritoneum. Bupivacaine in a concentration of 5
      mg/ml will be used and 5 ml of the solution will be injected at each port site. The patients
      who get placebo will get 5 ml of physiologic saline injected at each port site.

      The primary outcome of the study will be movement-evoked pain (MEP) 5 hours after surgery, as
      half-life of bupivacaine is 4-6 hours. Movement-evoked pain is the most important outcome
      measure, because the goal is to get the patient back to normal, daily activities as soon as
      possible. Trials measuring both movement evoked pain and pain at rest (PAR) suggests that MEP
      is much more intense than PAR postoperative (Srikandarajah et al, 2011). Pain will be
      measured on a 10 cm long Numerical Rating Scale (NRS) where 0 cm is no pain and 10 cm is
      severe pain. NRS is validated as a good tool for pain measurement at different ages and
      education levels (Gagliese et al, 2005).

      Secondary outcome measures will be pain at rest at 2 and 5 hours postoperative, and use of
      rescue analgesics. Pain at rest must, of course, be recorded before movement evoked pain.

      The pain scoring will be done by the patient with help from the nurses at the ward at 2 and 5
      hours postoperative, and both will be blinded to which arm the patient is in.
allocation: Randomized
intervention model: Parallel Assignment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Postoperative movement-evoked pain
time frame: 5 hours postoperative
description: The primary outcome of the study will be movement-evoked pain (MEP) 5 hours after surgery, as half-life of bupivacaine is 4-6 hours. Movement-evoked pain is the most important outcome measure, because the goal is to get the patient back to normal, daily activities as soon as possible.
measure: Pain at rest
time frame: 2 and 5 hours postoperative
description: Secondary outcome measures will be pain at rest at 2 and 5 hours postoperative.
measure: Rescue analgetics
time frame: 5 hours postoperative
description: Use of rescue analgesics postoperative.
arm group label: bupivacaine
arm group type: Active Comparator
description: Injection of 5 ml bupivacaine, 5mg/ml in each port site.
arm group label: Placebo
arm group type: Placebo Comparator
description: Injection of 5 ml saline in each port site.
intervention type: Drug
intervention name: Bupivacaine 5mg/ml
description: 5 ml in trocar area
arm group label: Placebo
arm group label: bupivacaine
other name: Marcain
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Caroline Ravndal, MD
role: Principal Investigator
affiliation: Helse Stavanger HF
facility: 
country: Norway
responsible party type: Sponsor
mesh term: Pain, Postoperative
mesh term: Bupivacaine