<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/NCT03751423</url>
  </required_header>
  <id_info>
    <org_study_id>OBGY-KET-18</org_study_id>
    <nct_id>NCT03751423</nct_id>
  </id_info>
  <brief_title>Intravenous Ketamine for Pain Control During First Trimester Surgical Abortion</brief_title>
  <official_title>Intravenous Ketamine for Pain Control During First Trimester Surgical Abortion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr. Marie Eve Sophie Bussiere-Cote</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Queen's University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      A therapeutic abortion is one of the most common procedures performed in Canada, with&#xD;
      approximately 100,000 occurring annually. 95% of induced abortions are done surgically, with&#xD;
      just over two thirds of these procedures taking place in the first trimester.&#xD;
&#xD;
      This study will be a randomized, controlled, double-blinded, single-centre superiority trial&#xD;
      with three parallel groups; oral morphine vs intravenous fentanyl vs intravenous ketamine.&#xD;
      The primary outcome will be immediate post-operative pain following a first trimester&#xD;
      therapeutic abortion as assessed using the visual analogue scale. Randomization will be&#xD;
      performed as block randomization with a 1:1:1 allocation ratio. In total, 123 participants&#xD;
      will be recruited and randomized, with 41 being assigned to each treatment arm. This study&#xD;
      will be conducted at the Women's Clinic at Kingston General Hospital in Kingston, Ontario,&#xD;
      Canada. Women from Kingston and the surrounding areas are referred to this clinic and can&#xD;
      self-refer for therapeutic abortion.&#xD;
&#xD;
      The investogators hope that this research will move us towards a better form of pain control&#xD;
      for our participants undergoing first trimester surgical abortion, without increasing length&#xD;
      of stay, side effects, or adverse events. This, in turn, will hopefully improve access to&#xD;
      optimal pain control to participants undergoing first trimester surgical abortion in an&#xD;
      outpatient setting.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale:&#xD;
&#xD;
      At present, the gold standard for pain control during first trimester abortion is the&#xD;
      combination of a paracervical block with moderate intravenous (IV) sedation. Paracervical&#xD;
      blocks are routinely done with lidocaine, with or without epinephrine or vasopressin.&#xD;
      Moderate sedation is commonly achieved using fentanyl 50-100ug IV and midazolam 1-2mg IV. The&#xD;
      issue with the use of IV opioids for sedation is the need for continuous cardio-respiratory&#xD;
      monitoring, due to the risk of cardio-respiratory depression or collapse. This therefore&#xD;
      limits the ability of some centers to provide the best form of pain control for their&#xD;
      participants undergoing first trimester surgical abortion. For instance, our center currently&#xD;
      uses a paracervical block plus a combination of oral medications (morphine and lorazepam),&#xD;
      which has been found to be inferior to a paracervical block plus IV sedation. All&#xD;
      participants without contraindications to NSAIDs are pre-medicated with naproxen as&#xD;
      recommended.2 The investigators also have access to nitrous oxide/oxygen 50:50 (Entonox) to&#xD;
      use as an adjunct, however this has not been found to significantly improve procedural or&#xD;
      post-operative pain.&#xD;
&#xD;
      In the past, ketamine was used for pain control during first trimester abortion. Ketamine is&#xD;
      a dissociative agent and does not carry the same risk of cardio-respiratory depression as&#xD;
      intravenous opioids. Ketamine was felt to be ideal for first trimester surgical abortion -as&#xD;
      the medication has uterotonic properties, which could result in less blood loss. Doses of&#xD;
      0.5mg/kg IV were typically used. However, the use of ketamine for first trimester surgical&#xD;
      abortion decreased dramatically after the 1970-1980's due to reports of adverse events&#xD;
      including emergence phenomena (nightmares), nausea, and vomiting. In fact, only one study&#xD;
      published during this time did not find negative emergence phenomena in participants exposed&#xD;
      to ketamine. More recently, a systematic review concluded that ketamine was an inferior agent&#xD;
      when compared to propofol for pain control during first trimester surgical abortion. However,&#xD;
      propofol, a general anesthetic requiring continuous cardio-respiratory monitoring, should not&#xD;
      be placed in the same anesthetic category as ketamine. Furthermore, propofol is only&#xD;
      available in a limited number of settings offering first trimester surgical abortion.&#xD;
&#xD;
      Over the last 10 to 15 years, ketamine has become an increasingly commonly used dissociative&#xD;
      agent for procedural sedation in the emergency department. The benefits of its use include&#xD;
      the simultaneous provision of both sedation and analgesia, while maintaining airway reflexes&#xD;
      and respiratory drive. Intravenous ketamine use in the emergency department has been shown to&#xD;
      yield high success rates (94% to 100%). In addition, of all the drugs commonly used in this&#xD;
      setting, ketamine has one of the highest safety profiles and lowest rates of complications.&#xD;
&#xD;
      The investigators are interested in re-visiting whether ketamine would be an appropriate&#xD;
      choice of anesthetic for first trimester surgical abortion. If ketamine is found to be&#xD;
      superior to IV fentanyl, it would potentially increase access to optimal pain control in&#xD;
      settings where continuous cardio-respiratory monitoring is not available. Furthermore, in the&#xD;
      current era of opioid misuse, it is important that providers look for alternative forms of&#xD;
      pain management when appropriate. In fact, the Society for Family Planning recently put out a&#xD;
      call to action for more research on alternative options to control pain short of moderate or&#xD;
      deep sedation.&#xD;
&#xD;
      Study Setting:&#xD;
&#xD;
      This study will be conducted at the Women's Clinic at Kingston General Hospital in Kingston,&#xD;
      Ontario, Canada. Women from Kingston and the surrounding areas are referred to this clinic&#xD;
      and can self-refer for therapeutic abortion.&#xD;
&#xD;
      Study Drugs:&#xD;
&#xD;
        -  PO Morphine&#xD;
&#xD;
        -  IV Fentanyl&#xD;
&#xD;
        -  IV Ketamine&#xD;
&#xD;
        -  PO Placebo&#xD;
&#xD;
        -  IV Placebo&#xD;
&#xD;
      Administration of Study Drugs:&#xD;
&#xD;
      Once written informed consent is received the care provider will determine opiate&#xD;
      sensitization stratum and write orders for the appropriate amount of oral morphine to be&#xD;
      dispensed to the participant.&#xD;
&#xD;
      The next sequential randomization envelope for the appropriate stratum will then be&#xD;
      retrieved. Within the randomization envelope there will be two envelopes, one for nursing&#xD;
      staff and one for the anesthetist. Drug dispensing will be done in two stages.&#xD;
&#xD;
      Nursing staff will open their envelope to determine from which drawer they are to dispense&#xD;
      the oral morphine dose ordered by the care provider (A, B or C). Two will be placebo and one&#xD;
      will be oral morphine, but nursing staff will be blinded to group assignment.&#xD;
&#xD;
      The anesthetist will open her envelope prior to the procedure to determine group assignment.&#xD;
      She will be responsible for the mixing and administration of all IV medications and will not&#xD;
      be blinded to group assignment. All other study staff, clinical staff and the participant&#xD;
      will remain blinded to group assignment.&#xD;
&#xD;
      Nursing staff will be responsible for dispensing and administering all other standard&#xD;
      medications including dimenhydrinate, naproxen, lorazepam and misoprostol.&#xD;
&#xD;
      For all participants the anesthetist will prepare IV medications according to participant&#xD;
      group assignment, ketamine, fentanyl or normal saline only. The syringes will be labelled&#xD;
      with the participant's name and hospital identification number. The syringes will be used for&#xD;
      IV drug administration during the procedure. Naloxone and/or midazolam will be administered&#xD;
      as needed at the discretion of the anesthetist.&#xD;
&#xD;
      Standard Script:&#xD;
&#xD;
      Prior to starting the procedure, the physician administrating sedation during the procedure&#xD;
      will inquire into some of the participant's favorite places and/or ideas, as this will be&#xD;
      used to individualize guided imagery for each participant during the procedure. An example of&#xD;
      such guided imagery during the procedure may include the physician asking the participant to&#xD;
      feel the sand on her feet at her favorite beach, to hear the waves landing on the shore, and&#xD;
      to feel the warmth of the sun on her skin. In addition to guided imagery performed during the&#xD;
      procedure, the voices in the room will be minimized only to necessary communication in a calm&#xD;
      gentle tone, and soothing music will be played quietly in the background. The guided imagery&#xD;
      and room setup will be used for all participants, regardless of the study drug that they&#xD;
      receive.&#xD;
&#xD;
      Consent Process:&#xD;
&#xD;
      Once the participant registers at the Women's Clinic, she will be asked by the nurse at&#xD;
      intake if she would be interested in participating in the research study. If she is&#xD;
      agreeable, the surgeon will proceed with the consent process.&#xD;
&#xD;
      If the participant consents to participate in the study, the surgeon will administer a&#xD;
      questionnaire to obtain a thorough medical history, collect information on participant&#xD;
      demographics and determine whether the participant is opiate naïve or opiate sensitized.&#xD;
&#xD;
      Randomization:&#xD;
&#xD;
      Participants will be randomized to one of three treatment arms following receipt of written&#xD;
      informed consent.&#xD;
&#xD;
      Allocation Sequence Generation:&#xD;
&#xD;
      The allocation sequence will be generated by an epidemiologist in the Department of&#xD;
      Obstetrics and Gynecology at Queen's University. Randomization will be blocked and&#xD;
      stratified. Stratification will be based on the participant's current opiate usage to ensure&#xD;
      that participants who are opiate sensitized are evenly distributed between the groups. Unique&#xD;
      allocation sequences will be generated for each stratum. Random block sizes of 3 and 6 will&#xD;
      be used for each of the sequences. For both sequences, participants will be allocated in a&#xD;
      1:1:1 ratio, with equal chance of being assigned to all three groups. An appropriate&#xD;
      statistical program will be used to generate the two allocation sequences.&#xD;
&#xD;
      Randomization Process:&#xD;
&#xD;
      Randomization will be done with consecutively numbered opaque envelopes. Research staff will&#xD;
      assemble these envelopes based on the two allocation sequences. The envelopes will be clearly&#xD;
      labelled with the stratum (opiate sensitized or naïve). Within each envelope there will be&#xD;
      two envelopes, one for nursing staff and one for the anesthetist. A sheet within the envelope&#xD;
      for the nursing staff will indicate from which drawer they are to dispense the oral morphine&#xD;
      (A, B, C). This will be done to ensure that nursing staff remains blinded to group&#xD;
      assignment. A sheet inside the envelope for the anesthetist will indicate arm allocation (PO&#xD;
      morphine, IV ketamine, IV fentanyl). The envelopes and sheets will be identical, except for&#xD;
      the number and strata label on the outside and text on the sheet inside, to minimize the&#xD;
      chance of accidental unblinding.&#xD;
&#xD;
      Upon receipt of written informed consent, the care provider will determine whether the&#xD;
      participant is opiate sensitized or naïve and write an order for an oral morphine dose. The&#xD;
      participant will be randomized by selecting the next envelope in the sequence of the&#xD;
      appropriate stratum based on the consecutive numbering. Nursing staff will open their labeled&#xD;
      envelope to determine from where to dispense the oral morphine. The anesthetist will open her&#xD;
      envelope to determine the participant's group allocation and dispense the appropriate IV&#xD;
      medications. Both envelopes will then be sealed and place in the participants chart. The&#xD;
      envelopes will only be opened in the case of emergency unblinding or by study staff for data&#xD;
      entry at a later date.&#xD;
&#xD;
      The Procedure:&#xD;
&#xD;
      The participant will undergo her procedure with the pain control regimen based on the&#xD;
      randomization. The anesthetist will maintain a drug administration log throughout the&#xD;
      procedure, including the use of any reversal agents. The total amounts of drugs mixed, used&#xD;
      and wasted will be recorded in this log. Only the anesthetist will have access to this log in&#xD;
      order to maintain blinding. It will be sealed and kept in the participants chart after the&#xD;
      procedure is complete. It will only be opened if emergency unblinding is required or by&#xD;
      research staff for data entry at a later date.&#xD;
&#xD;
      Once the procedure is complete, the nurse and/or surgeon will administer the immediate&#xD;
      post-operative pain assessment. The surgeon will record their assessment of intra-operative&#xD;
      pain management and their guess as to group assignment. Any adverse events or medication side&#xD;
      effects during the procedure will be recorded by the clinical team (nurses and surgeons).&#xD;
&#xD;
      The Recovery Room:&#xD;
&#xD;
      In the recovery room, the clinical team (nurses and surgeons) will record any side effects or&#xD;
      adverse events. Length of stay in recovery will be recorded in minutes by the nursing staff.&#xD;
      The participant will be administered a final pain assessment by nursing staff prior to&#xD;
      discharge. The participant will also be given a self-administered questionnaire with&#xD;
      questions about participant satisfaction, likelihood of using the same pain regimen at a&#xD;
      future procedure, and their guess regarding their group assignment.&#xD;
&#xD;
      Follow-Up:&#xD;
&#xD;
      The participant will be contacted by a member of the research team within 2-4 weeks of the&#xD;
      procedure. This will be done by telephone. The participant will be asked a series of&#xD;
      questions relating to satisfaction, complications that may have arisen following discharge,&#xD;
      the likelihood of using the same pain regimen at a future procedure, and their guess&#xD;
      regarding their group assignment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Study on-hold due to COVID-19 pandemic restrictions. Will resume when possible.&#xD;
  </why_stopped>
  <start_date type="Actual">June 10, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>This study will be a randomized, controlled, double-blinded, single-centre superiority trial with three parallel groups.</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    <masking_description>For the three treatment arms, the nurses, the study participants, and the abortion provider will be blinded to study arm assignment and will remain blinded throughout the course of the study. As such, all study personnel who will be administering questionnaires will be appropriately blinded to minimize bias. The provider of the IV medications will not be blinded. This decision was made in order to ensure participant safety in titrating medication doses, and to avoid the need to unblind all members if a reversal agent is required. The provider of the anesthetic will not disclose which study arm the participant belongs to and will not be involved in administering questionnaires or data analysis.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>VAS Pain Score - Immediate Post-Procedure</measure>
    <time_frame>Immediate Post-Procedure</time_frame>
    <description>The primary outcome measure is mean difference in immediate post-operative pain measured by the visual analogue pain scale (VAS). The VAS is a validated tool for research in operative pain management. Using this scale, participants rate their current pain on a scale from 0 to 10 by drawing an &quot;x&quot; on the horizontal line. This line is 10cm long and the participant's pain level is measured using a ruler to the millimeter mark and translated to a score out of 100mm. If the &quot;x&quot; falls between millimeter marks on the ruler the reader will round up to the nearest mark.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>VAS Pain Score - Prior to Discharge</measure>
    <time_frame>Prior to discharge from recovery room on day of procedure (typically within 1h post-procedure)</time_frame>
    <description>This secondary outcome will post-operative pain prior to discharge measured by the visual analogue pain scale (VAS). The VAS is a validated tool for research in operative pain management. Using this scale, participants rate their current pain on a scale from 0 to 10 by drawing an &quot;x&quot; on the horizontal line. This line is 10cm long and the participant's pain level is measured using a ruler to the millimeter mark and translated to a score out of 100mm. If the &quot;x&quot; falls between millimeter marks on the ruler the reader will round up to the nearest mark.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Stay in Recovery</measure>
    <time_frame>Day of Procedure</time_frame>
    <description>Length of stay in recovery in minutes from transfer from the procedure room till discharge.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Satisfaction with Pain Control - Prior to Discharge</measure>
    <time_frame>Prior to discharge from recovery room on day of procedure (typically within 1h post-procedure)</time_frame>
    <description>Satisfaction with pain control will be assessed using a 5-point Likert scale. 1 is the worst score and 5 is the best.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medication Side Effects</measure>
    <time_frame>Prior to discharge from recovery room on day of procedure (typically within 1h post-procedure)</time_frame>
    <description>Medication side effects from administration till discharge as reported by the care providers and nurses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Provider Assessment of Intra-Operative Pain Management</measure>
    <time_frame>Intra-Operative</time_frame>
    <description>Provider assessment of intra-operative pain will be reported using a 5-point Likert scale. 1 is the worst score and 5 is the best.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wong-Baker Faces Pain Score - Immediate Post-Procedure</measure>
    <time_frame>Immediate Post-Procedure</time_frame>
    <description>Pain score will immediate post-procedure will also be reported using the Wong-Baker Faces Pain Rating Scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wong-Baker Faces Pain Score - Prior to Discharge</measure>
    <time_frame>Prior to discharge from recovery room on day of procedure (typically within 1h post-procedure)</time_frame>
    <description>Pain score will prior to discharge will also be reported using the Wong-Baker Faces Pain Rating Scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Control After Discharge</measure>
    <time_frame>2-4 weeks post-procedure</time_frame>
    <description>Pain control after discharge will be assessed via telephone questionnaire using a 5-point Likert scale. 1 is the worst score and 5 is the best.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Satisfaction with Pain Control After Discharge</measure>
    <time_frame>2-4 weeks post-procedure</time_frame>
    <description>Satisfaction with pain control after discharge will be assessed via telephone questionnaire using a 5-point Likert scale.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">123</enrollment>
  <condition>Abortion in First Trimester</condition>
  <arm_group>
    <arm_group_label>PO Morphine &amp; IV Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>One third of study participants will be randomized to this local standard of care arm.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IV Fentanyl &amp; PO Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>One third of study participants will be randomized to this current gold standard of care arm.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IV Ketamine &amp; PO Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One third of study participants will be randomized to this experimental arm.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PO Morphine</intervention_name>
    <description>10-20mg oral morphine depending on such factors as weight (100-200mcg/kg), previous opiate exposure (opiate naïve vs opiate sensitized), and participant's previous experiences with opiate medications for painful procedures. Dosing will be determined at the discretion of the surgical provider in clinic that day, as per standard of care.</description>
    <arm_group_label>PO Morphine &amp; IV Placebo</arm_group_label>
    <other_name>Morphine Sulphate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IV Fentanyl</intervention_name>
    <description>0.5-1mcg/kg IV fentanyl over 2 minutes repeated every 5 minutes as needed until appropriate analgesia is reached.</description>
    <arm_group_label>IV Fentanyl &amp; PO Placebo</arm_group_label>
    <other_name>Fentanyl Citrate Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IV Ketamine</intervention_name>
    <description>200-500mcg/kg IV over 2 minutes repeated every 5 minutes as needed until appropriate analgesia is reached</description>
    <arm_group_label>IV Ketamine &amp; PO Placebo</arm_group_label>
    <other_name>Ketamine Hydrochloride Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PO Placebo</intervention_name>
    <description>A standard placebo pill, the same size, shape and colour of the oral morphine. The placebo will be administered to the participants randomized to the IV ketamine and IV fentanyl during pre-op in the same manner the oral morphine would be administered.</description>
    <arm_group_label>IV Fentanyl &amp; PO Placebo</arm_group_label>
    <arm_group_label>IV Ketamine &amp; PO Placebo</arm_group_label>
    <other_name>Oral Placebo Pill</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IV Placebo</intervention_name>
    <description>This normal saline will be administered to the participants randomized to the oral morphine group during the procedure in the same manner that IV fentanyl or IV ketamine would be administered.</description>
    <arm_group_label>PO Morphine &amp; IV Placebo</arm_group_label>
    <other_name>Normal Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Confirmed first trimester pregnancy with an ultrasound showing a viable intrauterine&#xD;
             pregnancy with a gestational age of less than 12 weeks since the last menstrual period&#xD;
&#xD;
          2. Unwanted pregnancy and consented to undergo a first trimester surgical abortion&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age &lt;18 years at the time of study enrollment&#xD;
&#xD;
          2. Known allergy or sensitivity to any of the medications used in the study&#xD;
&#xD;
          3. Any serious medical comorbidity that would make IV sedation contraindicated in an&#xD;
             outpatient setting (ex. Heart disease, lung disease)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sophie Bussiere-Cote, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Queen's University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ashley Waddington, MD, MPA</last_name>
    <role>Principal Investigator</role>
    <affiliation>Queen's University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Queen's University</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <zip>K7L2V7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Induced abortions reported in Canada in 2016. Ottawa: Canadian Institute for Health Information; 2018. Available at: https://www.cihi.ca/en/induced-abortions-reported-in-canada-in-2016. Accessed on July 29, 2018.</citation>
  </reference>
  <reference>
    <citation>Costescu D, Guilbert E. No. 360-Induced Abortion: Surgical Abortion and Second Trimester Medical Methods. J Obstet Gynaecol Can. 2018 Jun;40(6):750-783. doi: 10.1016/j.jogc.2017.12.010.</citation>
    <PMID>29861084</PMID>
  </reference>
  <reference>
    <citation>Allen RH, Fitzmaurice G, Lifford KL, Lasic M, Goldberg AB. Oral compared with intravenous sedation for first-trimester surgical abortion: a randomized controlled trial. Obstet Gynecol. 2009 Feb;113(2 Pt 1):276-83. doi: 10.1097/AOG.0b013e3181938758.</citation>
    <PMID>19155895</PMID>
  </reference>
  <reference>
    <citation>Agostini A, Maruani J, Roblin P, Champion J, Cravello L, Gamerre M. A double-blind, randomized controlled trial of the use of a 50:50 mixture of nitrous oxide/oxygen in legal abortions. Contraception. 2012 Jul;86(1):79-83. doi: 10.1016/j.contraception.2011.11.015. Epub 2012 Jan 20.</citation>
    <PMID>22264664</PMID>
  </reference>
  <reference>
    <citation>Kan AS, Caves N, Wong SY, Ng EH, Ho PC. A double-blind, randomized controlled trial on the use of a 50:50 mixture of nitrous oxide/oxygen in pain relief during suction evacuation for the first trimester pregnancy termination. Hum Reprod. 2006 Oct;21(10):2606-11. doi: 10.1093/humrep/del234. Epub 2006 Jun 21.</citation>
    <PMID>16790607</PMID>
  </reference>
  <reference>
    <citation>Strayer RJ, Nelson LS. Adverse events associated with ketamine for procedural sedation in adults. Am J Emerg Med. 2008 Nov;26(9):985-1028. doi: 10.1016/j.ajem.2007.12.005. Erratum In: Am J Emerg Med. 2009 May;27(4):512.</citation>
    <PMID>19091264</PMID>
  </reference>
  <reference>
    <citation>Galloon S. Ketamine for dilatation and curettage. Can Anaesth Soc J. 1971 Nov;18(6):600-13. doi: 10.1007/BF03026180. No abstract available.</citation>
    <PMID>5119802</PMID>
  </reference>
  <reference>
    <citation>Hejja P, Galloon S. A consideration of ketamine dreams. Can Anaesth Soc J. 1975 Jan;22(1):100-5. doi: 10.1007/BF03004825.</citation>
    <PMID>1109698</PMID>
  </reference>
  <reference>
    <citation>Erbguth PH, Reiman B, Klein RL. The influence of chlorpromazine, diazepam, and droperidol on emergence from ketamine. Anesth Analg. 1972 Sep-Oct;51(5):693-700. No abstract available.</citation>
    <PMID>4560720</PMID>
  </reference>
  <reference>
    <citation>Hervey WH, Hustead RF. Ketamine for dilatation and currettage procedures: patient acceptance. Anesth Analg. 1972 Jul-Aug;51(4):647-55.</citation>
    <PMID>5064798</PMID>
  </reference>
  <reference>
    <citation>Krestow M. The effect of post-anaesthetic dreaming on patient acceptance of ketamine anaesthesia: a comparison with thiopentone-nitrous oxide anaesthesia. Can Anaesth Soc J. 1974 Jul;21(4):385-9. doi: 10.1007/BF03006072. No abstract available.</citation>
    <PMID>4836917</PMID>
  </reference>
  <reference>
    <citation>Freuchen I, Ostergaard J, Kuhl JB, Mikkelsen BO. Reduction of psychotomimetic side effects of Ketalar (ketamine) by Rohypnol (flunitrazepam). A randomized, double-blind trial. Acta Anaesthesiol Scand. 1976;20(2):97-103. doi: 10.1111/j.1399-6576.1976.tb05015.x.</citation>
    <PMID>7095</PMID>
  </reference>
  <reference>
    <citation>Coad NR, Mills PJ, Verma R, Ramasubramanian R. Evaluation of blood loss during suction termination of pregnancy: ketamine compared with methohexitone. Acta Anaesthesiol Scand. 1986 Apr;30(3):253-5. doi: 10.1111/j.1399-6576.1986.tb02407.x.</citation>
    <PMID>3739583</PMID>
  </reference>
  <reference>
    <citation>Renner RM, Jensen JT, Nichols MD, Edelman AB. Pain control in first-trimester surgical abortion: a systematic review of randomized controlled trials. Contraception. 2010 May;81(5):372-88. doi: 10.1016/j.contraception.2009.12.008. Epub 2010 Jan 27.</citation>
    <PMID>20399943</PMID>
  </reference>
  <reference>
    <citation>Godwin SA, Burton JH, Gerardo CJ, Hatten BW, Mace SE, Silvers SM, Fesmire FM; American College of Emergency Physicians. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2014 Feb;63(2):247-58.e18. doi: 10.1016/j.annemergmed.2013.10.015. Erratum In: Ann Emerg Med. 2017 Nov;70(5):758.</citation>
    <PMID>24438649</PMID>
  </reference>
  <reference>
    <citation>Atkinson P, French J, Nice CA. Procedural sedation and analgesia for adults in the emergency department. BMJ. 2014 May 8;348:g2965. doi: 10.1136/bmj.g2965. No abstract available. Erratum In: BMJ. 2015;350:h1007.</citation>
    <PMID>24812113</PMID>
  </reference>
  <reference>
    <citation>Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med. 2011 May;57(5):449-61. doi: 10.1016/j.annemergmed.2010.11.030. Epub 2011 Jan 21.</citation>
    <PMID>21256625</PMID>
  </reference>
  <reference>
    <citation>Newton A, Fitton L. Intravenous ketamine for adult procedural sedation in the emergency department: a prospective cohort study. Emerg Med J. 2008 Aug;25(8):498-501. doi: 10.1136/emj.2007.053421.</citation>
    <PMID>18660398</PMID>
  </reference>
  <reference>
    <citation>Coralic Z, Sawe HR, Mfinanga JA, Cortez A, Koehl J, Siroker H, Reynolds TA. Ketamine procedural sedation in the emergency department of an urban tertiary hospital in Dar es Salaam, Tanzania. Emerg Med J. 2018 Apr;35(4):214-219. doi: 10.1136/emermed-2017-206974. Epub 2018 Jan 22.</citation>
    <PMID>29358491</PMID>
  </reference>
  <reference>
    <citation>Bisanzo M, Nichols K, Hammerstedt H, Dreifuss B, Nelson SW, Chamberlain S, Kyomugisha F, Noble A, Arthur A, Thomas S. Nurse-administered ketamine sedation in an emergency department in rural Uganda. Ann Emerg Med. 2012 Apr;59(4):268-75. doi: 10.1016/j.annemergmed.2011.11.004. Epub 2011 Dec 9.</citation>
    <PMID>22169331</PMID>
  </reference>
  <reference>
    <citation>Sacchetti A, Senula G, Strickland J, Dubin R. Procedural sedation in the community emergency department: initial results of the ProSCED registry. Acad Emerg Med. 2007 Jan;14(1):41-6. doi: 10.1197/j.aem.2006.05.023. Epub 2006 Aug 31.</citation>
    <PMID>16946280</PMID>
  </reference>
  <reference>
    <citation>Allen RH, Singh R. Society of Family Planning clinical guidelines pain control in surgical abortion part 1 - local anesthesia and minimal sedation. Contraception. 2018 Jun;97(6):471-477. doi: 10.1016/j.contraception.2018.01.014. Epub 2018 Jan 31.</citation>
    <PMID>29407363</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>September 7, 2022</last_update_submitted>
  <last_update_submitted_qc>September 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Queen's University</investigator_affiliation>
    <investigator_full_name>Dr. Marie Eve Sophie Bussiere-Cote</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>procedural sedation</keyword>
  <keyword>ketamine</keyword>
  <keyword>fentanyl</keyword>
  <keyword>morphine</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Ketamine</mesh_term>
    <mesh_term>Morphine</mesh_term>
  </intervention_browse>
  <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/NCT03751423
org study id: OBGY-KET-18
nct id: NCT03751423
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A therapeutic abortion is one of the most common procedures performed in Canada, with
      approximately 100,000 occurring annually. 95% of induced abortions are done surgically, with
      just over two thirds of these procedures taking place in the first trimester.

      This study will be a randomized, controlled, double-blinded, single-centre superiority trial
      with three parallel groups; oral morphine vs intravenous fentanyl vs intravenous ketamine.
      The primary outcome will be immediate post-operative pain following a first trimester
      therapeutic abortion as assessed using the visual analogue scale. Randomization will be
      performed as block randomization with a 1:1:1 allocation ratio. In total, 123 participants
      will be recruited and randomized, with 41 being assigned to each treatment arm. This study
      will be conducted at the Women's Clinic at Kingston General Hospital in Kingston, Ontario,
      Canada. Women from Kingston and the surrounding areas are referred to this clinic and can
      self-refer for therapeutic abortion.

      The investogators hope that this research will move us towards a better form of pain control
      for our participants undergoing first trimester surgical abortion, without increasing length
      of stay, side effects, or adverse events. This, in turn, will hopefully improve access to
      optimal pain control to participants undergoing first trimester surgical abortion in an
      outpatient setting.
Rationale:

      At present, the gold standard for pain control during first trimester abortion is the
      combination of a paracervical block with moderate intravenous (IV) sedation. Paracervical
      blocks are routinely done with lidocaine, with or without epinephrine or vasopressin.
      Moderate sedation is commonly achieved using fentanyl 50-100ug IV and midazolam 1-2mg IV. The
      issue with the use of IV opioids for sedation is the need for continuous cardio-respiratory
      monitoring, due to the risk of cardio-respiratory depression or collapse. This therefore
      limits the ability of some centers to provide the best form of pain control for their
      participants undergoing first trimester surgical abortion. For instance, our center currently
      uses a paracervical block plus a combination of oral medications (morphine and lorazepam),
      which has been found to be inferior to a paracervical block plus IV sedation. All
      participants without contraindications to NSAIDs are pre-medicated with naproxen as
      recommended.2 The investigators also have access to nitrous oxide/oxygen 50:50 (Entonox) to
      use as an adjunct, however this has not been found to significantly improve procedural or
      post-operative pain.

      In the past, ketamine was used for pain control during first trimester abortion. Ketamine is
      a dissociative agent and does not carry the same risk of cardio-respiratory depression as
      intravenous opioids. Ketamine was felt to be ideal for first trimester surgical abortion -as
      the medication has uterotonic properties, which could result in less blood loss. Doses of
      0.5mg/kg IV were typically used. However, the use of ketamine for first trimester surgical
      abortion decreased dramatically after the 1970-1980's due to reports of adverse events
      including emergence phenomena (nightmares), nausea, and vomiting. In fact, only one study
      published during this time did not find negative emergence phenomena in participants exposed
      to ketamine. More recently, a systematic review concluded that ketamine was an inferior agent
      when compared to propofol for pain control during first trimester surgical abortion. However,
      propofol, a general anesthetic requiring continuous cardio-respiratory monitoring, should not
      be placed in the same anesthetic category as ketamine. Furthermore, propofol is only
      available in a limited number of settings offering first trimester surgical abortion.

      Over the last 10 to 15 years, ketamine has become an increasingly commonly used dissociative
      agent for procedural sedation in the emergency department. The benefits of its use include
      the simultaneous provision of both sedation and analgesia, while maintaining airway reflexes
      and respiratory drive. Intravenous ketamine use in the emergency department has been shown to
      yield high success rates (94% to 100%). In addition, of all the drugs commonly used in this
      setting, ketamine has one of the highest safety profiles and lowest rates of complications.

      The investigators are interested in re-visiting whether ketamine would be an appropriate
      choice of anesthetic for first trimester surgical abortion. If ketamine is found to be
      superior to IV fentanyl, it would potentially increase access to optimal pain control in
      settings where continuous cardio-respiratory monitoring is not available. Furthermore, in the
      current era of opioid misuse, it is important that providers look for alternative forms of
      pain management when appropriate. In fact, the Society for Family Planning recently put out a
      call to action for more research on alternative options to control pain short of moderate or
      deep sedation.

      Study Setting:

      This study will be conducted at the Women's Clinic at Kingston General Hospital in Kingston,
      Ontario, Canada. Women from Kingston and the surrounding areas are referred to this clinic
      and can self-refer for therapeutic abortion.

      Study Drugs:

        -  PO Morphine

        -  IV Fentanyl

        -  IV Ketamine

        -  PO Placebo

        -  IV Placebo

      Administration of Study Drugs:

      Once written informed consent is received the care provider will determine opiate
      sensitization stratum and write orders for the appropriate amount of oral morphine to be
      dispensed to the participant.

      The next sequential randomization envelope for the appropriate stratum will then be
      retrieved. Within the randomization envelope there will be two envelopes, one for nursing
      staff and one for the anesthetist. Drug dispensing will be done in two stages.

      Nursing staff will open their envelope to determine from which drawer they are to dispense
      the oral morphine dose ordered by the care provider (A, B or C). Two will be placebo and one
      will be oral morphine, but nursing staff will be blinded to group assignment.

      The anesthetist will open her envelope prior to the procedure to determine group assignment.
      She will be responsible for the mixing and administration of all IV medications and will not
      be blinded to group assignment. All other study staff, clinical staff and the participant
      will remain blinded to group assignment.

      Nursing staff will be responsible for dispensing and administering all other standard
      medications including dimenhydrinate, naproxen, lorazepam and misoprostol.

      For all participants the anesthetist will prepare IV medications according to participant
      group assignment, ketamine, fentanyl or normal saline only. The syringes will be labelled
      with the participant's name and hospital identification number. The syringes will be used for
      IV drug administration during the procedure. Naloxone and/or midazolam will be administered
      as needed at the discretion of the anesthetist.

      Standard Script:

      Prior to starting the procedure, the physician administrating sedation during the procedure
      will inquire into some of the participant's favorite places and/or ideas, as this will be
      used to individualize guided imagery for each participant during the procedure. An example of
      such guided imagery during the procedure may include the physician asking the participant to
      feel the sand on her feet at her favorite beach, to hear the waves landing on the shore, and
      to feel the warmth of the sun on her skin. In addition to guided imagery performed during the
      procedure, the voices in the room will be minimized only to necessary communication in a calm
      gentle tone, and soothing music will be played quietly in the background. The guided imagery
      and room setup will be used for all participants, regardless of the study drug that they
      receive.

      Consent Process:

      Once the participant registers at the Women's Clinic, she will be asked by the nurse at
      intake if she would be interested in participating in the research study. If she is
      agreeable, the surgeon will proceed with the consent process.

      If the participant consents to participate in the study, the surgeon will administer a
      questionnaire to obtain a thorough medical history, collect information on participant
      demographics and determine whether the participant is opiate naïve or opiate sensitized.

      Randomization:

      Participants will be randomized to one of three treatment arms following receipt of written
      informed consent.

      Allocation Sequence Generation:

      The allocation sequence will be generated by an epidemiologist in the Department of
      Obstetrics and Gynecology at Queen's University. Randomization will be blocked and
      stratified. Stratification will be based on the participant's current opiate usage to ensure
      that participants who are opiate sensitized are evenly distributed between the groups. Unique
      allocation sequences will be generated for each stratum. Random block sizes of 3 and 6 will
      be used for each of the sequences. For both sequences, participants will be allocated in a
      1:1:1 ratio, with equal chance of being assigned to all three groups. An appropriate
      statistical program will be used to generate the two allocation sequences.

      Randomization Process:

      Randomization will be done with consecutively numbered opaque envelopes. Research staff will
      assemble these envelopes based on the two allocation sequences. The envelopes will be clearly
      labelled with the stratum (opiate sensitized or naïve). Within each envelope there will be
      two envelopes, one for nursing staff and one for the anesthetist. A sheet within the envelope
      for the nursing staff will indicate from which drawer they are to dispense the oral morphine
      (A, B, C). This will be done to ensure that nursing staff remains blinded to group
      assignment. A sheet inside the envelope for the anesthetist will indicate arm allocation (PO
      morphine, IV ketamine, IV fentanyl). The envelopes and sheets will be identical, except for
      the number and strata label on the outside and text on the sheet inside, to minimize the
      chance of accidental unblinding.

      Upon receipt of written informed consent, the care provider will determine whether the
      participant is opiate sensitized or naïve and write an order for an oral morphine dose. The
      participant will be randomized by selecting the next envelope in the sequence of the
      appropriate stratum based on the consecutive numbering. Nursing staff will open their labeled
      envelope to determine from where to dispense the oral morphine. The anesthetist will open her
      envelope to determine the participant's group allocation and dispense the appropriate IV
      medications. Both envelopes will then be sealed and place in the participants chart. The
      envelopes will only be opened in the case of emergency unblinding or by study staff for data
      entry at a later date.

      The Procedure:

      The participant will undergo her procedure with the pain control regimen based on the
      randomization. The anesthetist will maintain a drug administration log throughout the
      procedure, including the use of any reversal agents. The total amounts of drugs mixed, used
      and wasted will be recorded in this log. Only the anesthetist will have access to this log in
      order to maintain blinding. It will be sealed and kept in the participants chart after the
      procedure is complete. It will only be opened if emergency unblinding is required or by
      research staff for data entry at a later date.

      Once the procedure is complete, the nurse and/or surgeon will administer the immediate
      post-operative pain assessment. The surgeon will record their assessment of intra-operative
      pain management and their guess as to group assignment. Any adverse events or medication side
      effects during the procedure will be recorded by the clinical team (nurses and surgeons).

      The Recovery Room:

      In the recovery room, the clinical team (nurses and surgeons) will record any side effects or
      adverse events. Length of stay in recovery will be recorded in minutes by the nursing staff.
      The participant will be administered a final pain assessment by nursing staff prior to
      discharge. The participant will also be given a self-administered questionnaire with
      questions about participant satisfaction, likelihood of using the same pain regimen at a
      future procedure, and their guess regarding their group assignment.

      Follow-Up:

      The participant will be contacted by a member of the research team within 2-4 weeks of the
      procedure. This will be done by telephone. The participant will be asked a series of
      questions relating to satisfaction, complications that may have arisen following discharge,
      the likelihood of using the same pain regimen at a future procedure, and their guess
      regarding their group assignment.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This study will be a randomized, controlled, double-blinded, single-centre superiority trial with three parallel groups.
primary purpose: Supportive Care
masking: Triple (Participant, Care Provider, Outcomes Assessor)
masking description: For the three treatment arms, the nurses, the study participants, and the abortion provider will be blinded to study arm assignment and will remain blinded throughout the course of the study. As such, all study personnel who will be administering questionnaires will be appropriately blinded to minimize bias. The provider of the IV medications will not be blinded. This decision was made in order to ensure participant safety in titrating medication doses, and to avoid the need to unblind all members if a reversal agent is required. The provider of the anesthetic will not disclose which study arm the participant belongs to and will not be involved in administering questionnaires or data analysis.
measure: VAS Pain Score - Immediate Post-Procedure
time frame: Immediate Post-Procedure
description: The primary outcome measure is mean difference in immediate post-operative pain measured by the visual analogue pain scale (VAS). The VAS is a validated tool for research in operative pain management. Using this scale, participants rate their current pain on a scale from 0 to 10 by drawing an "x" on the horizontal line. This line is 10cm long and the participant's pain level is measured using a ruler to the millimeter mark and translated to a score out of 100mm. If the "x" falls between millimeter marks on the ruler the reader will round up to the nearest mark.
measure: VAS Pain Score - Prior to Discharge
time frame: Prior to discharge from recovery room on day of procedure (typically within 1h post-procedure)
description: This secondary outcome will post-operative pain prior to discharge measured by the visual analogue pain scale (VAS). The VAS is a validated tool for research in operative pain management. Using this scale, participants rate their current pain on a scale from 0 to 10 by drawing an "x" on the horizontal line. This line is 10cm long and the participant's pain level is measured using a ruler to the millimeter mark and translated to a score out of 100mm. If the "x" falls between millimeter marks on the ruler the reader will round up to the nearest mark.
measure: Length of Stay in Recovery
time frame: Day of Procedure
description: Length of stay in recovery in minutes from transfer from the procedure room till discharge.
measure: Satisfaction with Pain Control - Prior to Discharge
time frame: Prior to discharge from recovery room on day of procedure (typically within 1h post-procedure)
description: Satisfaction with pain control will be assessed using a 5-point Likert scale. 1 is the worst score and 5 is the best.
measure: Medication Side Effects
time frame: Prior to discharge from recovery room on day of procedure (typically within 1h post-procedure)
description: Medication side effects from administration till discharge as reported by the care providers and nurses.
measure: Provider Assessment of Intra-Operative Pain Management
time frame: Intra-Operative
description: Provider assessment of intra-operative pain will be reported using a 5-point Likert scale. 1 is the worst score and 5 is the best.
measure: Wong-Baker Faces Pain Score - Immediate Post-Procedure
time frame: Immediate Post-Procedure
description: Pain score will immediate post-procedure will also be reported using the Wong-Baker Faces Pain Rating Scale.
measure: Wong-Baker Faces Pain Score - Prior to Discharge
time frame: Prior to discharge from recovery room on day of procedure (typically within 1h post-procedure)
description: Pain score will prior to discharge will also be reported using the Wong-Baker Faces Pain Rating Scale.
measure: Pain Control After Discharge
time frame: 2-4 weeks post-procedure
description: Pain control after discharge will be assessed via telephone questionnaire using a 5-point Likert scale. 1 is the worst score and 5 is the best.
measure: Satisfaction with Pain Control After Discharge
time frame: 2-4 weeks post-procedure
description: Satisfaction with pain control after discharge will be assessed via telephone questionnaire using a 5-point Likert scale.
arm group label: PO Morphine & IV Placebo
arm group type: Active Comparator
description: One third of study participants will be randomized to this local standard of care arm.
arm group label: IV Fentanyl & PO Placebo
arm group type: Active Comparator
description: One third of study participants will be randomized to this current gold standard of care arm.
arm group label: IV Ketamine & PO Placebo
arm group type: Experimental
description: One third of study participants will be randomized to this experimental arm.
intervention type: Drug
intervention name: PO Morphine
description: 10-20mg oral morphine depending on such factors as weight (100-200mcg/kg), previous opiate exposure (opiate naïve vs opiate sensitized), and participant's previous experiences with opiate medications for painful procedures. Dosing will be determined at the discretion of the surgical provider in clinic that day, as per standard of care.
arm group label: PO Morphine & IV Placebo
other name: Morphine Sulphate
intervention type: Drug
intervention name: IV Fentanyl
description: 0.5-1mcg/kg IV fentanyl over 2 minutes repeated every 5 minutes as needed until appropriate analgesia is reached.
arm group label: IV Fentanyl & PO Placebo
other name: Fentanyl Citrate Injection
intervention type: Drug
intervention name: IV Ketamine
description: 200-500mcg/kg IV over 2 minutes repeated every 5 minutes as needed until appropriate analgesia is reached
arm group label: IV Ketamine & PO Placebo
other name: Ketamine Hydrochloride Injection
intervention type: Drug
intervention name: PO Placebo
description: A standard placebo pill, the same size, shape and colour of the oral morphine. The placebo will be administered to the participants randomized to the IV ketamine and IV fentanyl during pre-op in the same manner the oral morphine would be administered.
arm group label: IV Fentanyl & PO Placebo
arm group label: IV Ketamine & PO Placebo
other name: Oral Placebo Pill
intervention type: Drug
intervention name: IV Placebo
description: This normal saline will be administered to the participants randomized to the oral morphine group during the procedure in the same manner that IV fentanyl or IV ketamine would be administered.
arm group label: PO Morphine & IV Placebo
other name: Normal Saline
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sophie Bussiere-Cote, MD
role: Principal Investigator
affiliation: Queen's University
last name: Ashley Waddington, MD, MPA
role: Principal Investigator
affiliation: Queen's University
facility: 
country: Canada
citation: Induced abortions reported in Canada in 2016. Ottawa: Canadian Institute for Health Information; 2018. Available at: https://www.cihi.ca/en/induced-abortions-reported-in-canada-in-2016. Accessed on July 29, 2018.
citation: Costescu D, Guilbert E. No. 360-Induced Abortion: Surgical Abortion and Second Trimester Medical Methods. J Obstet Gynaecol Can. 2018 Jun;40(6):750-783. doi: 10.1016/j.jogc.2017.12.010.
PMID: 29861084
citation: Allen RH, Fitzmaurice G, Lifford KL, Lasic M, Goldberg AB. Oral compared with intravenous sedation for first-trimester surgical abortion: a randomized controlled trial. Obstet Gynecol. 2009 Feb;113(2 Pt 1):276-83. doi: 10.1097/AOG.0b013e3181938758.
PMID: 19155895
citation: Agostini A, Maruani J, Roblin P, Champion J, Cravello L, Gamerre M. A double-blind, randomized controlled trial of the use of a 50:50 mixture of nitrous oxide/oxygen in legal abortions. Contraception. 2012 Jul;86(1):79-83. doi: 10.1016/j.contraception.2011.11.015. Epub 2012 Jan 20.
PMID: 22264664
citation: Kan AS, Caves N, Wong SY, Ng EH, Ho PC. A double-blind, randomized controlled trial on the use of a 50:50 mixture of nitrous oxide/oxygen in pain relief during suction evacuation for the first trimester pregnancy termination. Hum Reprod. 2006 Oct;21(10):2606-11. doi: 10.1093/humrep/del234. Epub 2006 Jun 21.
PMID: 16790607
citation: Strayer RJ, Nelson LS. Adverse events associated with ketamine for procedural sedation in adults. Am J Emerg Med. 2008 Nov;26(9):985-1028. doi: 10.1016/j.ajem.2007.12.005. Erratum In: Am J Emerg Med. 2009 May;27(4):512.
PMID: 19091264
citation: Galloon S. Ketamine for dilatation and curettage. Can Anaesth Soc J. 1971 Nov;18(6):600-13. doi: 10.1007/BF03026180. No abstract available.
PMID: 5119802
citation: Hejja P, Galloon S. A consideration of ketamine dreams. Can Anaesth Soc J. 1975 Jan;22(1):100-5. doi: 10.1007/BF03004825.
PMID: 1109698
citation: Erbguth PH, Reiman B, Klein RL. The influence of chlorpromazine, diazepam, and droperidol on emergence from ketamine. Anesth Analg. 1972 Sep-Oct;51(5):693-700. No abstract available.
PMID: 4560720
citation: Hervey WH, Hustead RF. Ketamine for dilatation and currettage procedures: patient acceptance. Anesth Analg. 1972 Jul-Aug;51(4):647-55.
PMID: 5064798
citation: Krestow M. The effect of post-anaesthetic dreaming on patient acceptance of ketamine anaesthesia: a comparison with thiopentone-nitrous oxide anaesthesia. Can Anaesth Soc J. 1974 Jul;21(4):385-9. doi: 10.1007/BF03006072. No abstract available.
PMID: 4836917
citation: Freuchen I, Ostergaard J, Kuhl JB, Mikkelsen BO. Reduction of psychotomimetic side effects of Ketalar (ketamine) by Rohypnol (flunitrazepam). A randomized, double-blind trial. Acta Anaesthesiol Scand. 1976;20(2):97-103. doi: 10.1111/j.1399-6576.1976.tb05015.x.
PMID: 7095
citation: Coad NR, Mills PJ, Verma R, Ramasubramanian R. Evaluation of blood loss during suction termination of pregnancy: ketamine compared with methohexitone. Acta Anaesthesiol Scand. 1986 Apr;30(3):253-5. doi: 10.1111/j.1399-6576.1986.tb02407.x.
PMID: 3739583
citation: Renner RM, Jensen JT, Nichols MD, Edelman AB. Pain control in first-trimester surgical abortion: a systematic review of randomized controlled trials. Contraception. 2010 May;81(5):372-88. doi: 10.1016/j.contraception.2009.12.008. Epub 2010 Jan 27.
PMID: 20399943
citation: Godwin SA, Burton JH, Gerardo CJ, Hatten BW, Mace SE, Silvers SM, Fesmire FM; American College of Emergency Physicians. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2014 Feb;63(2):247-58.e18. doi: 10.1016/j.annemergmed.2013.10.015. Erratum In: Ann Emerg Med. 2017 Nov;70(5):758.
PMID: 24438649
citation: Atkinson P, French J, Nice CA. Procedural sedation and analgesia for adults in the emergency department. BMJ. 2014 May 8;348:g2965. doi: 10.1136/bmj.g2965. No abstract available. Erratum In: BMJ. 2015;350:h1007.
PMID: 24812113
citation: Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med. 2011 May;57(5):449-61. doi: 10.1016/j.annemergmed.2010.11.030. Epub 2011 Jan 21.
PMID: 21256625
citation: Newton A, Fitton L. Intravenous ketamine for adult procedural sedation in the emergency department: a prospective cohort study. Emerg Med J. 2008 Aug;25(8):498-501. doi: 10.1136/emj.2007.053421.
PMID: 18660398
citation: Coralic Z, Sawe HR, Mfinanga JA, Cortez A, Koehl J, Siroker H, Reynolds TA. Ketamine procedural sedation in the emergency department of an urban tertiary hospital in Dar es Salaam, Tanzania. Emerg Med J. 2018 Apr;35(4):214-219. doi: 10.1136/emermed-2017-206974. Epub 2018 Jan 22.
PMID: 29358491
citation: Bisanzo M, Nichols K, Hammerstedt H, Dreifuss B, Nelson SW, Chamberlain S, Kyomugisha F, Noble A, Arthur A, Thomas S. Nurse-administered ketamine sedation in an emergency department in rural Uganda. Ann Emerg Med. 2012 Apr;59(4):268-75. doi: 10.1016/j.annemergmed.2011.11.004. Epub 2011 Dec 9.
PMID: 22169331
citation: Sacchetti A, Senula G, Strickland J, Dubin R. Procedural sedation in the community emergency department: initial results of the ProSCED registry. Acad Emerg Med. 2007 Jan;14(1):41-6. doi: 10.1197/j.aem.2006.05.023. Epub 2006 Aug 31.
PMID: 16946280
citation: Allen RH, Singh R. Society of Family Planning clinical guidelines pain control in surgical abortion part 1 - local anesthesia and minimal sedation. Contraception. 2018 Jun;97(6):471-477. doi: 10.1016/j.contraception.2018.01.014. Epub 2018 Jan 31.
PMID: 29407363
responsible party type: Sponsor-Investigator
investigator affiliation: Queen's University
investigator full name: Dr. Marie Eve Sophie Bussiere-Cote
investigator title: Principal Investigator
mesh term: Fentanyl
mesh term: Ketamine
mesh term: Morphine
sharing ipd: Undecided