<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/NCT04459377</url>
  </required_header>
  <id_info>
    <org_study_id>20140929sketamine</org_study_id>
    <secondary_id>2014-004235-39</secondary_id>
    <nct_id>NCT04459377</nct_id>
  </id_info>
  <brief_title>Ketamine Analgesia in Third Molar Surgery</brief_title>
  <official_title>An Analysis of Ketamine Analgesia in Third Molar Surgery -Effects, Safety and Influence on Inflammatory Biomarkers in Plasma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dalarna County Council, Sweden</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Uppsala University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Center for Clinical Research Dalarna, Sweden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Dalarna County Council, Sweden</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>
      BACKGROUND AND PURPOSE Outpatient surgery (day case surgery) is increasing. When the patients&#xD;
      go home on the same day, this demands safe pain relief. A reduction of morphine (opioid) use&#xD;
      is sought because of side effects and the dependency risk. An effective alternative to&#xD;
      opioids is ketamine, which lacks the side effects of opioids but provides powerful analgesic&#xD;
      effects.&#xD;
&#xD;
      METHOD At the start of surgery, Ketamine or placebo will be given in a vein to evaluate if&#xD;
      the acute pain decreases significantly. Inflammation is known to cause pain. By measuring&#xD;
      different proteins in the blood, the investigators want to understand how inflammation links&#xD;
      to the pain. Wisdom tooth surgery provides significant post-operative pain and is a widely&#xD;
      accepted pain model in drug studies. Patients referred for wisdom tooth surgery are asked to&#xD;
      participate in the study. For statistical certainty, in total 165 persons will be enrolled to&#xD;
      three groups. Two with active drug (different dose) and one placebo. Everyone gets local&#xD;
      anesthesia. The completion of the study will be done in four years. The Ethics Review Board&#xD;
      has approved the study.&#xD;
&#xD;
      CLINICAL RELEVANCE Effective pain relief after daily surgical procedures is important for&#xD;
      patient´s safety and reducing the risk of long-term pain. It is also ethically necessary for&#xD;
      the continued expansion of day case surgery. New knowledge of the mechanisms of pain&#xD;
      increases the opportunities for individual and safe pain relief. Day case surgery is&#xD;
      performed in all operating specialties, this might affects many patients nationally and&#xD;
      internationally.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 14, 2017</start_date>
  <completion_date type="Actual">September 30, 2022</completion_date>
  <primary_completion_date type="Actual">March 10, 2022</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>Pain (VAS)</measure>
    <time_frame>4 hours postoperatively</time_frame>
    <description>Postoperative pain measured by Visual analog scale (VAS). From minimum 0mm to maximum 100mm. 0mm is no pain and 100mm is worst pain imaginable. Changes in Visual Analog Scale value from preoperatively to 4 hours postoperatively</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety (Oxygen saturation)</measure>
    <time_frame>Up to 2 hours.</time_frame>
    <description>Change in oxygen saturation measured by pulseoximeter %. Intra individually and between the groups. From start to completion of the ketamine infusion.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">168</enrollment>
  <condition>Pain</condition>
  <condition>Postoperative</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Sodium Chloride solution (9mg / ml) 0.2ml / kg slow intravenous injection (2ml / min).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>K1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>S-Ketamine (0.125 mg / kg body weight). (0.625mg / ml x 0.2ml / kg) slow intravenous injection (2ml / min).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>K2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>S-Ketamine (0.25 mg / kg body weight). (1.25mg / ml x 0.2ml / kg) slow intravenous injection (2ml / min).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>S-Ketamine</intervention_name>
    <description>Patients are randomized to three groups. Randomization in blocks of six patients stratified by sex. A list of serial numbers and randomized group affiliation is produced which is open to the pharmacy's manufacturing staff and closed to the staff of the trial. The pharmacy prepares filled syringes with investigation drug in accordance with randomized group affiliation.&#xD;
All groups are sedated with midazolam intravenously to a defined end point. A syringe pump with volume accuracy ± 2% injects the test drug (P, K1 or K2). One infusion set is coupled between the syringe and a three-way connection, which in turn is connected to a peripheral venous catheter (PVK). This PVK is also used for blood sampling. Blood is sampled at two occasions. Directly preoperatively and two hours after surgery. The third molar is surgically removed.</description>
    <arm_group_label>K1</arm_group_label>
    <arm_group_label>K2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Chloride 0.9% Inj</intervention_name>
    <description>Patients are randomized to three groups. Randomization in blocks of six patients stratified by sex. A list of serial numbers and randomized group affiliation is produced which is open to the pharmacy's manufacturing staff and closed to the staff of the trial. The pharmacy prepares filled syringes with investigation drug in accordance with randomized group affiliation.&#xD;
All groups are sedated with midazolam intravenously to a defined end point. A syringe pump with volume accuracy ± 2% injects the test drug (P, K1 or K2). One infusion set is coupled between the syringe and a three-way connection, which in turn is connected to a peripheral venous catheter (PVK). This PVK is also used for blood sampling. Blood is sampled at two occasions. Directly preoperatively and two hours after surgery. The third molar is surgically removed.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy or mild well-compensated systemic disease (ASA I &amp; II)&#xD;
&#xD;
          -  18- &lt;45 years&#xD;
&#xD;
          -  50-100 kg body weight&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Medication drugs: analgesics, hypnotics (the last week before surgery), thyroid&#xD;
             hormones, psychoactive drugs or monoamine oxidase inhibitors (MAO inhibitors).&#xD;
&#xD;
          -  Hypertension [&gt; 150/95 mmHg in screening study]&#xD;
&#xD;
          -  Heart failure&#xD;
&#xD;
          -  Psychosis&#xD;
&#xD;
          -  Epilepsy&#xD;
&#xD;
          -  Hyperthyreosis&#xD;
&#xD;
          -  Myasthenia gravis&#xD;
&#xD;
          -  Glaucoma&#xD;
&#xD;
          -  Verified sleep apnea&#xD;
&#xD;
          -  Diabetes (insulin treated)&#xD;
&#xD;
          -  Porphyria&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Breast-feeding&#xD;
&#xD;
          -  Blood transmitted infections, such as HIV and hepatitis B and C&#xD;
&#xD;
          -  Known hypersensitivity to midazolam, ketamine, ibuprofen, or local anesthetics&#xD;
&#xD;
          -  Inability to obtain the requisite written or oral information&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>44 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lars Sand, Professor, DDS, MD</last_name>
    <role>Study Director</role>
    <affiliation>Uppsala University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Käkkirurgiska kliniken, Falu lasarett</name>
      <address>
        <city>Falun</city>
        <state>Dalarna</state>
        <zip>79182</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>October 10, 2022</last_update_submitted>
  <last_update_submitted_qc>October 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dalarna County Council, Sweden</investigator_affiliation>
    <investigator_full_name>Lars Eriksson</investigator_full_name>
    <investigator_title>Senior Consultant in Oral and Maxillofacial Surgery</investigator_title>
  </responsible_party>
  <keyword>Ketamine</keyword>
  <keyword>Postoperative</keyword>
  <keyword>Pain management</keyword>
  <keyword>Third molar</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
    <mesh_term>Esketamine</mesh_term>
  </intervention_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/NCT04459377
org study id: 20140929sketamine
secondary id: 2014-004235-39
nct id: NCT04459377
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
BACKGROUND AND PURPOSE Outpatient surgery (day case surgery) is increasing. When the patients
      go home on the same day, this demands safe pain relief. A reduction of morphine (opioid) use
      is sought because of side effects and the dependency risk. An effective alternative to
      opioids is ketamine, which lacks the side effects of opioids but provides powerful analgesic
      effects.

      METHOD At the start of surgery, Ketamine or placebo will be given in a vein to evaluate if
      the acute pain decreases significantly. Inflammation is known to cause pain. By measuring
      different proteins in the blood, the investigators want to understand how inflammation links
      to the pain. Wisdom tooth surgery provides significant post-operative pain and is a widely
      accepted pain model in drug studies. Patients referred for wisdom tooth surgery are asked to
      participate in the study. For statistical certainty, in total 165 persons will be enrolled to
      three groups. Two with active drug (different dose) and one placebo. Everyone gets local
      anesthesia. The completion of the study will be done in four years. The Ethics Review Board
      has approved the study.

      CLINICAL RELEVANCE Effective pain relief after daily surgical procedures is important for
      patient´s safety and reducing the risk of long-term pain. It is also ethically necessary for
      the continued expansion of day case surgery. New knowledge of the mechanisms of pain
      increases the opportunities for individual and safe pain relief. Day case surgery is
      performed in all operating specialties, this might affects many patients nationally and
      internationally.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Pain (VAS)
time frame: 4 hours postoperatively
description: Postoperative pain measured by Visual analog scale (VAS). From minimum 0mm to maximum 100mm. 0mm is no pain and 100mm is worst pain imaginable. Changes in Visual Analog Scale value from preoperatively to 4 hours postoperatively
measure: Safety (Oxygen saturation)
time frame: Up to 2 hours.
description: Change in oxygen saturation measured by pulseoximeter %. Intra individually and between the groups. From start to completion of the ketamine infusion.
arm group label: Placebo
arm group type: Placebo Comparator
description: Sodium Chloride solution (9mg / ml) 0.2ml / kg slow intravenous injection (2ml / min).
arm group label: K1
arm group type: Active Comparator
description: S-Ketamine (0.125 mg / kg body weight). (0.625mg / ml x 0.2ml / kg) slow intravenous injection (2ml / min).
arm group label: K2
arm group type: Active Comparator
description: S-Ketamine (0.25 mg / kg body weight). (1.25mg / ml x 0.2ml / kg) slow intravenous injection (2ml / min).
intervention type: Drug
intervention name: S-Ketamine
description: Patients are randomized to three groups. Randomization in blocks of six patients stratified by sex. A list of serial numbers and randomized group affiliation is produced which is open to the pharmacy's manufacturing staff and closed to the staff of the trial. The pharmacy prepares filled syringes with investigation drug in accordance with randomized group affiliation.
All groups are sedated with midazolam intravenously to a defined end point. A syringe pump with volume accuracy ± 2% injects the test drug (P, K1 or K2). One infusion set is coupled between the syringe and a three-way connection, which in turn is connected to a peripheral venous catheter (PVK). This PVK is also used for blood sampling. Blood is sampled at two occasions. Directly preoperatively and two hours after surgery. The third molar is surgically removed.
arm group label: K1
arm group label: K2
intervention type: Drug
intervention name: Sodium Chloride 0.9% Inj
description: Patients are randomized to three groups. Randomization in blocks of six patients stratified by sex. A list of serial numbers and randomized group affiliation is produced which is open to the pharmacy's manufacturing staff and closed to the staff of the trial. The pharmacy prepares filled syringes with investigation drug in accordance with randomized group affiliation.
All groups are sedated with midazolam intravenously to a defined end point. A syringe pump with volume accuracy ± 2% injects the test drug (P, K1 or K2). One infusion set is coupled between the syringe and a three-way connection, which in turn is connected to a peripheral venous catheter (PVK). This PVK is also used for blood sampling. Blood is sampled at two occasions. Directly preoperatively and two hours after surgery. The third molar is surgically removed.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 44 Years
healthy volunteers: No
last name: Lars Sand, Professor, DDS, MD
role: Study Director
affiliation: Uppsala University
facility: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Dalarna County Council, Sweden
investigator full name: Lars Eriksson
investigator title: Senior Consultant in Oral and Maxillofacial Surgery
mesh term: Ketamine
mesh term: Esketamine
sharing ipd: No