<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/NCT03841409</url>
  </required_header>
  <id_info>
    <org_study_id>18.308</org_study_id>
    <nct_id>NCT03841409</nct_id>
  </id_info>
  <brief_title>Peak Plasma Levels of Bupivacaine After an Erector Spinae Block (ESP)</brief_title>
  <official_title>Peak Plasma Levels of Bupivacaine After an Erector Spinae Block</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre hospitalier de l'Université de Montréal (CHUM)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre hospitalier de l'Université de Montréal (CHUM)</source>
  <oversight_info>
    <has_dmc>No</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 primary objective of the study is to measure plasma levels of bupivacaine following&#xD;
      erector spinae (ESP) regional block in patients undergoing mastectomy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Breast cancer is one of the most frequent types of cancer in women. Mastectomy is important&#xD;
      in treating these cases; however, sometimes it is associated with acute and chronic pain.&#xD;
      Multimodal analgesia, combining drug therapy and regional anesthesia, can help in preventing&#xD;
      acute and perhaps chronic pain in breast cancer patients undergoing mastectomy.&#xD;
&#xD;
      Erector spinae block is a new regional anesthesia technique that has emerged to treat&#xD;
      thoracic pain following thoracic and breast surgery. It consists of injecting local&#xD;
      anesthetics in the space located between the erector and paravertebral muscles using&#xD;
      ultrasound guidance. The injection can be done at the level of T5 allowing distribution of&#xD;
      the drug to upper and lower dermatomes.&#xD;
&#xD;
      The dose of local anesthetic injected after erector spinae block should aim to maximize&#xD;
      analgesia while minimizing the chance of toxic systemic concentrations. Defining the rate of&#xD;
      absorption of local anesthetics into the blood after an erector spinae block will therefore&#xD;
      help anesthesiologists determinate optimal analgesic doses, in terms of both safety and&#xD;
      effectiveness.&#xD;
&#xD;
      This observational study will determine bupivacaine pharmacokinetics after single shot&#xD;
      erector spinae block with bupivacaine, to further define the right dose and duration of&#xD;
      surveillance in post-anesthesia care.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      For the erector spinae block, the patient will be placed in the sitting position. Using an&#xD;
      ultrasound machine with a high frequency linear probe (Sonosite, HFL50 15-6MHz) placed in the&#xD;
      parasagittal plane, 3cm away from the midline, the anesthesiologist will position an&#xD;
      insulated hyperechoic needle (50-80 mm, 22 gauge, SonoPlex STIM, Nanoline, Pajun, Germany) at&#xD;
      the level of the 5th thoracic vertebrae, between the erector spinae and the paravertebral&#xD;
      muscles. The anesthesiologist will confirm the correct position of the needle with the&#xD;
      injection of 1 mL of 5% dextrose. Then, after negative aspiration, he will inject bupivacaine&#xD;
      0.5% with epinephrine 5 mcg/mL in 5 ml aliquots for a total dose of 2mg/kg of ideal body&#xD;
      weight (maximum of 150mg).&#xD;
&#xD;
      The end of injection will be considered as T0. Collection of 4.5mL of blood will be performed&#xD;
      at T10min, T20min, T30min, T45min, T60min, T90min, T120min, T180min, and T240min.&#xD;
&#xD;
      Blood tubes will be immediately placed on ice to be ultimately sent to the laboratory for&#xD;
      centrifugation and measurement of bupivacaine level using liquid chromatography-tandem mass&#xD;
      spectrometry (LC-MS/MS) for each of the samples.&#xD;
&#xD;
      General anesthesia will then be induced in the operating room with no additional bupivacaine&#xD;
      allowed by the anesthesiologist or the surgeon. After surgery, in the Post-Anesthesia Care&#xD;
      Unit, the level of the sensory block will be identified by pinprick and the quality of&#xD;
      analgesia will be evaluated using a verbal numerical rating scale, and opioid consumption&#xD;
      will be noted.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 14, 2019</start_date>
  <completion_date type="Actual">October 16, 2019</completion_date>
  <primary_completion_date type="Actual">October 16, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Maximal plasma concentration (Cmax) of bupivacaine after erector spinae block</measure>
    <time_frame>The end of injection of bupivacaine will be considered as T0. Blood samples at T10, T20, T30, T45, T60, T90, T120, T180, and T240minutes will be collected to further analyze plasmatic bupivacaine values at these timepoints.</time_frame>
    <description>The Cmax will be estimated by interpolation based on the plasmatic bupivacaine values obtained after the analysis of the blood samples.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time (Tmax) to maximum plasma concentration Cmax of bupivacaine</measure>
    <time_frame>The end of injection of bupivacaine will be considered as T0. Blood samples at T10, T20, T30, T45, T60, T90, T120, T180, and T240minutes will be performed to further analyze plasmatic bupivacaine values at these timepoints.</time_frame>
    <description>The Tmax will be estimated by interpolation based on the plasmatic bupivacaine values obtained after the analysis of the blood samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sensory block level 30 minutes after arriving to Post-Anesthesia Care Unit</measure>
    <time_frame>30 minutes after arriving to Post-Anesthesia Care Unit</time_frame>
    <description>Sensory block level will be measured with a 6.1g von Frey filaments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-operative pain using verbal numerical rating scale</measure>
    <time_frame>30 minutes after arriving to Post-Anesthesia Care Unit</time_frame>
    <description>The quality of postoperative analgesia at rest will be evaluated with a verbal numeric scale (VNS) where 0 represents 'no pain' and 10 represents 'the worst pain'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total opioid dose needed during Post-Anesthesia Care Unit stay (PACU)</measure>
    <time_frame>After the surgery, from the entry in the Post-Anesthesia Care Unit to the discharge from the Post-Anesthesia Care Unit, for an average of one-hour stay.</time_frame>
    <description>The total dose of opioids used by the patients during the PACU stay will be recorded.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">18</enrollment>
  <condition>Pharmacokinetics</condition>
  <condition>Anesthesia, Local</condition>
  <arm_group>
    <arm_group_label>Bupivacaine dosage in ESP block</arm_group_label>
    <description>The pharmacokinetics of bupivacaine 0.5% with epinephrine 5 mcg/mL for a total dose of 2mg/kg of ideal body weight following an ESP block will be determined by the collection of blood samples at predetermined time points.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Collection of blood samples</intervention_name>
    <description>Nine blood samples will be collected to determine bupivacaine pharmacokinetics at T10min, T20min, T30min, T45min, T60min, T90min, T120min, T180min, and T240min. T0 will be defined as the end of bupivacaine injection.</description>
    <arm_group_label>Bupivacaine dosage in ESP block</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients undergoing unilateral mastectomy under general anesthesia and erector spinae block&#xD;
        for post-operative pain management.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ASA I-III&#xD;
&#xD;
          -  Undergoing unilateral mastectomy under erector spinae block and general anesthesia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient's refusal or inability to consent&#xD;
&#xD;
          -  Allergy, hypersensibility or resistance to local anesthetic&#xD;
&#xD;
          -  Contra-indication to regional anesthesia: infection in the designated area, acquired&#xD;
             or congenital coagulopathy&#xD;
&#xD;
          -  Severe hepatic or renal insufficiency (GFR&lt;30 mL/min)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephan Williams, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre hospitalier de l'Université de Montréal (CHUM)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Université de Montréal (CHUM)</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H2X 3E4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>February 11, 2019</study_first_submitted>
  <study_first_submitted_qc>February 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>May 27, 2022</last_update_submitted>
  <last_update_submitted_qc>May 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03841409
org study id: 18.308
nct id: NCT03841409
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objective of the study is to measure plasma levels of bupivacaine following
      erector spinae (ESP) regional block in patients undergoing mastectomy.
Breast cancer is one of the most frequent types of cancer in women. Mastectomy is important
      in treating these cases; however, sometimes it is associated with acute and chronic pain.
      Multimodal analgesia, combining drug therapy and regional anesthesia, can help in preventing
      acute and perhaps chronic pain in breast cancer patients undergoing mastectomy.

      Erector spinae block is a new regional anesthesia technique that has emerged to treat
      thoracic pain following thoracic and breast surgery. It consists of injecting local
      anesthetics in the space located between the erector and paravertebral muscles using
      ultrasound guidance. The injection can be done at the level of T5 allowing distribution of
      the drug to upper and lower dermatomes.

      The dose of local anesthetic injected after erector spinae block should aim to maximize
      analgesia while minimizing the chance of toxic systemic concentrations. Defining the rate of
      absorption of local anesthetics into the blood after an erector spinae block will therefore
      help anesthesiologists determinate optimal analgesic doses, in terms of both safety and
      effectiveness.

      This observational study will determine bupivacaine pharmacokinetics after single shot
      erector spinae block with bupivacaine, to further define the right dose and duration of
      surveillance in post-anesthesia care.

      Methods:

      For the erector spinae block, the patient will be placed in the sitting position. Using an
      ultrasound machine with a high frequency linear probe (Sonosite, HFL50 15-6MHz) placed in the
      parasagittal plane, 3cm away from the midline, the anesthesiologist will position an
      insulated hyperechoic needle (50-80 mm, 22 gauge, SonoPlex STIM, Nanoline, Pajun, Germany) at
      the level of the 5th thoracic vertebrae, between the erector spinae and the paravertebral
      muscles. The anesthesiologist will confirm the correct position of the needle with the
      injection of 1 mL of 5% dextrose. Then, after negative aspiration, he will inject bupivacaine
      0.5% with epinephrine 5 mcg/mL in 5 ml aliquots for a total dose of 2mg/kg of ideal body
      weight (maximum of 150mg).

      The end of injection will be considered as T0. Collection of 4.5mL of blood will be performed
      at T10min, T20min, T30min, T45min, T60min, T90min, T120min, T180min, and T240min.

      Blood tubes will be immediately placed on ice to be ultimately sent to the laboratory for
      centrifugation and measurement of bupivacaine level using liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) for each of the samples.

      General anesthesia will then be induced in the operating room with no additional bupivacaine
      allowed by the anesthesiologist or the surgeon. After surgery, in the Post-Anesthesia Care
      Unit, the level of the sensory block will be identified by pinprick and the quality of
      analgesia will be evaluated using a verbal numerical rating scale, and opioid consumption
      will be noted.
observational model: Cohort
time perspective: Prospective
measure: Maximal plasma concentration (Cmax) of bupivacaine after erector spinae block
time frame: The end of injection of bupivacaine will be considered as T0. Blood samples at T10, T20, T30, T45, T60, T90, T120, T180, and T240minutes will be collected to further analyze plasmatic bupivacaine values at these timepoints.
description: The Cmax will be estimated by interpolation based on the plasmatic bupivacaine values obtained after the analysis of the blood samples.
measure: Time (Tmax) to maximum plasma concentration Cmax of bupivacaine
time frame: The end of injection of bupivacaine will be considered as T0. Blood samples at T10, T20, T30, T45, T60, T90, T120, T180, and T240minutes will be performed to further analyze plasmatic bupivacaine values at these timepoints.
description: The Tmax will be estimated by interpolation based on the plasmatic bupivacaine values obtained after the analysis of the blood samples.
measure: Sensory block level 30 minutes after arriving to Post-Anesthesia Care Unit
time frame: 30 minutes after arriving to Post-Anesthesia Care Unit
description: Sensory block level will be measured with a 6.1g von Frey filaments.
measure: Post-operative pain using verbal numerical rating scale
time frame: 30 minutes after arriving to Post-Anesthesia Care Unit
description: The quality of postoperative analgesia at rest will be evaluated with a verbal numeric scale (VNS) where 0 represents 'no pain' and 10 represents 'the worst pain'.
measure: Total opioid dose needed during Post-Anesthesia Care Unit stay (PACU)
time frame: After the surgery, from the entry in the Post-Anesthesia Care Unit to the discharge from the Post-Anesthesia Care Unit, for an average of one-hour stay.
description: The total dose of opioids used by the patients during the PACU stay will be recorded.
arm group label: Bupivacaine dosage in ESP block
description: The pharmacokinetics of bupivacaine 0.5% with epinephrine 5 mcg/mL for a total dose of 2mg/kg of ideal body weight following an ESP block will be determined by the collection of blood samples at predetermined time points.
intervention type: Other
intervention name: Collection of blood samples
description: Nine blood samples will be collected to determine bupivacaine pharmacokinetics at T10min, T20min, T30min, T45min, T60min, T90min, T120min, T180min, and T240min. T0 will be defined as the end of bupivacaine injection.
arm group label: Bupivacaine dosage in ESP block
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Stephan Williams, MD, PhD
role: Principal Investigator
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
facility: 
country: Canada
responsible party type: Sponsor
sharing ipd: Undecided