<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/NCT02995291</url>
  </required_header>
  <id_info>
    <org_study_id>2016-4014</org_study_id>
    <nct_id>NCT02995291</nct_id>
  </id_info>
  <brief_title>Reversing the Effects of 0.5% Bupivacaine</brief_title>
  <official_title>Reversing the Effects of 0.5% Bupivacaine: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dalhousie University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dalhousie University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Clinical trials have shown phentolamine mesylate (PM), brand name OraVerse, to be effective&#xD;
      at reducing the amount of time to reversal of local anesthesia with different dental&#xD;
      anesthetics. However, to date no study investigated the efficacy of phentolamine mesylate to&#xD;
      reverse anesthesia induced with the use of Bupivacaine.&#xD;
&#xD;
      The objective of the proposed research is to conduct a pilot-scale randomized clinical trial&#xD;
      evaluating the difference in time required for the return of normal soft-tissue sensation and&#xD;
      function in participants who have received 0.5% Bupivacaine HCl, 1:200,000 epinephrine,&#xD;
      followed by an injection with either 1) OraVerse (phentolamine mesylate) or 2) sterile&#xD;
      physiological water (control).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dental procedures often require the use of local anesthesia. The most common local anesthetic&#xD;
      used is 2% Lidocaine 1:100,000 epinephrine. This local anesthetic can achieve soft tissue&#xD;
      anesthesia for 180-300 minutes and pulpal anesthesia for 60 minutes. Unfortunately, for&#xD;
      longer treatments this relatively short duration can lead to the loss of anesthetic effect&#xD;
      before the end of the interventions. Time-demanding dental appointments include oral and&#xD;
      periodontal surgeries, extensive restorative treatments, and even minor treatments when&#xD;
      completed by dental students. Unfortunately, if a short acting anesthetic such as Lidocaine&#xD;
      is being used during long lasting procedures, once the patients start feeling pain again, it&#xD;
      may be difficult to reestablish deep pulpal anesthesia with a repeated injection due to&#xD;
      tachyphylaxis. To avoid this situation long-acting local anesthetics could be selected&#xD;
      instead. The only long-acting anesthetic available in dentistry is 0.5% Bupivacaine HCl,&#xD;
      1:200,000 epinephrine. Bupivacaine can produce soft tissue anesthesia for up to 12 hours&#xD;
      (commonly 4 to 9 hours) and pulpal anesthesia for up to 7 hours (commonly 1.5 to 3 hours).&#xD;
      Unfortunately, Bupivacaine is not often used for non-surgical procedures due to its very long&#xD;
      soft tissue anesthesia that outlast treatments by several hours.&#xD;
&#xD;
      The effects of soft tissue anesthesia linger for some time after the administration of long&#xD;
      acting local anesthetics such as Bupivacaine. This can lead to discomfort and occasionally&#xD;
      injury from lip/tongue biting. Clinical trials have shown phentolamine mesylate (PM), brand&#xD;
      name OraVerse, to be effective at reducing the amount of time to reversal of local anesthesia&#xD;
      with different dental anesthetics. However, to date no study investigated the efficacy of&#xD;
      phentolamine mesylate to reverse anesthesia induced with the use of Bupivacaine.&#xD;
&#xD;
      The objective of the proposed research is to conduct a pilot-scale randomized clinical trial&#xD;
      evaluating the difference in time required for the return of normal soft-tissue sensation and&#xD;
      function in participants who have received 0.5% Bupivacaine HCl, 1:200,000 epinephrine,&#xD;
      followed by an injection with either 1) OraVerse (phentolamine mesylate) or 2) sterile&#xD;
      physiological water (control). This will further advance our knowledge of both Bupivacaine&#xD;
      and phentolamine mesylate as there are no current studies evaluating reversing the effect of&#xD;
      Bupivacaine with PM.&#xD;
&#xD;
      It is hypothesized that phentolamine mesylate will reduce the duration of soft tissue&#xD;
      anesthesia by 2.5 hours when compared with a control injection of saline water. It is&#xD;
      anticipated that this study will determine the feasibility and sample size needed to conduct&#xD;
      a full-scale multi-centre trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 10, 2017</start_date>
  <completion_date type="Actual">September 15, 2019</completion_date>
  <primary_completion_date type="Actual">May 15, 2019</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to reversal of local anesthesia</measure>
    <time_frame>8 hours</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Anesthesia, Local</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1.7ml saline water</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OraVerse</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1.7ml OraVerse</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OraVerse</intervention_name>
    <description>1.7ml OraVerse (0.4 mg phentolamine mesylate) will be injected once after the participants are found to be well anesthetized following an injection of 1.8ml Bupivacaine 0.5% (inferior alveolar nerve block). Oraverse will be injected at the same site Bupivacaine was injected.</description>
    <arm_group_label>OraVerse</arm_group_label>
    <other_name>phentolamine mesylate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline Water (Control)</intervention_name>
    <description>1.7ml saline water will be injected once after the participants are found to be well anesthetized following an injection of 1.8ml Bupivacaine 0.5% (inferior alveolar nerve block). The water will be injected at the same site Bupivacaine was injected.</description>
    <arm_group_label>Control</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years of age or older&#xD;
&#xD;
          -  capable of providing informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  contra-indications for regular dental treatment&#xD;
&#xD;
          -  medical history that contraindicates the use of epinephrine&#xD;
&#xD;
          -  participant taken an opioid or an opioid like analgesic within 24 hours&#xD;
&#xD;
          -  pregnant&#xD;
      </textblock>
    </criteria>
    <gender>All</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>Pierre-Luc Michaud, DMD, MSc, FRCDC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dalhousie University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dalhousie University Faculty of Dentistry</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3H 4R2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>http://www.dal.ca/faculty/dentistry.html</url>
    <description>Dalhousie University Faculty of Dentistry Web Site</description>
  </link>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 16, 2016</study_first_posted>
  <last_update_submitted>January 27, 2020</last_update_submitted>
  <last_update_submitted_qc>January 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dalhousie University</investigator_affiliation>
    <investigator_full_name>Pierre-Luc Michaud</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Phentolamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Aggregate data to be published in peer reviewed journal</ipd_description>
  </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/NCT02995291
org study id: 2016-4014
nct id: NCT02995291
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Clinical trials have shown phentolamine mesylate (PM), brand name OraVerse, to be effective
      at reducing the amount of time to reversal of local anesthesia with different dental
      anesthetics. However, to date no study investigated the efficacy of phentolamine mesylate to
      reverse anesthesia induced with the use of Bupivacaine.

      The objective of the proposed research is to conduct a pilot-scale randomized clinical trial
      evaluating the difference in time required for the return of normal soft-tissue sensation and
      function in participants who have received 0.5% Bupivacaine HCl, 1:200,000 epinephrine,
      followed by an injection with either 1) OraVerse (phentolamine mesylate) or 2) sterile
      physiological water (control).
Dental procedures often require the use of local anesthesia. The most common local anesthetic
      used is 2% Lidocaine 1:100,000 epinephrine. This local anesthetic can achieve soft tissue
      anesthesia for 180-300 minutes and pulpal anesthesia for 60 minutes. Unfortunately, for
      longer treatments this relatively short duration can lead to the loss of anesthetic effect
      before the end of the interventions. Time-demanding dental appointments include oral and
      periodontal surgeries, extensive restorative treatments, and even minor treatments when
      completed by dental students. Unfortunately, if a short acting anesthetic such as Lidocaine
      is being used during long lasting procedures, once the patients start feeling pain again, it
      may be difficult to reestablish deep pulpal anesthesia with a repeated injection due to
      tachyphylaxis. To avoid this situation long-acting local anesthetics could be selected
      instead. The only long-acting anesthetic available in dentistry is 0.5% Bupivacaine HCl,
      1:200,000 epinephrine. Bupivacaine can produce soft tissue anesthesia for up to 12 hours
      (commonly 4 to 9 hours) and pulpal anesthesia for up to 7 hours (commonly 1.5 to 3 hours).
      Unfortunately, Bupivacaine is not often used for non-surgical procedures due to its very long
      soft tissue anesthesia that outlast treatments by several hours.

      The effects of soft tissue anesthesia linger for some time after the administration of long
      acting local anesthetics such as Bupivacaine. This can lead to discomfort and occasionally
      injury from lip/tongue biting. Clinical trials have shown phentolamine mesylate (PM), brand
      name OraVerse, to be effective at reducing the amount of time to reversal of local anesthesia
      with different dental anesthetics. However, to date no study investigated the efficacy of
      phentolamine mesylate to reverse anesthesia induced with the use of Bupivacaine.

      The objective of the proposed research is to conduct a pilot-scale randomized clinical trial
      evaluating the difference in time required for the return of normal soft-tissue sensation and
      function in participants who have received 0.5% Bupivacaine HCl, 1:200,000 epinephrine,
      followed by an injection with either 1) OraVerse (phentolamine mesylate) or 2) sterile
      physiological water (control). This will further advance our knowledge of both Bupivacaine
      and phentolamine mesylate as there are no current studies evaluating reversing the effect of
      Bupivacaine with PM.

      It is hypothesized that phentolamine mesylate will reduce the duration of soft tissue
      anesthesia by 2.5 hours when compared with a control injection of saline water. It is
      anticipated that this study will determine the feasibility and sample size needed to conduct
      a full-scale multi-centre trial.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time to reversal of local anesthesia
time frame: 8 hours
arm group label: Control
arm group type: Placebo Comparator
description: 1.7ml saline water
arm group label: OraVerse
arm group type: Experimental
description: 1.7ml OraVerse
intervention type: Drug
intervention name: OraVerse
description: 1.7ml OraVerse (0.4 mg phentolamine mesylate) will be injected once after the participants are found to be well anesthetized following an injection of 1.8ml Bupivacaine 0.5% (inferior alveolar nerve block). Oraverse will be injected at the same site Bupivacaine was injected.
arm group label: OraVerse
other name: phentolamine mesylate
intervention type: Drug
intervention name: Saline Water (Control)
description: 1.7ml saline water will be injected once after the participants are found to be well anesthetized following an injection of 1.8ml Bupivacaine 0.5% (inferior alveolar nerve block). The water will be injected at the same site Bupivacaine was injected.
arm group label: Control
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Pierre-Luc Michaud, DMD, MSc, FRCDC
role: Principal Investigator
affiliation: Dalhousie University
facility: 
country: Canada
url: http://www.dal.ca/faculty/dentistry.html
description: Dalhousie University Faculty of Dentistry Web Site
responsible party type: Principal Investigator
investigator affiliation: Dalhousie University
investigator full name: Pierre-Luc Michaud
investigator title: Assistant Professor
mesh term: Phentolamine
sharing ipd: No
ipd description: Aggregate data to be published in peer reviewed journal