<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/NCT04495374</url>
  </required_header>
  <id_info>
    <org_study_id>3.334.050</org_study_id>
    <nct_id>NCT04495374</nct_id>
  </id_info>
  <brief_title>Oral Pregabalin as Preemptive Analgesia in Abdominal Hysterectomy</brief_title>
  <official_title>Use of Oral Pregabalin as Preemptive Analgesia in Abdominal Hysterectomy: Evaluation of Postoperative Pain and Opioid Consumption</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidade Federal de Alfenas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universidade Federal de Alfenas</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Postoperative pain affects 80% of surgical patients and is one of the main negative symptoms&#xD;
      resulting from surgery. It impairs the recovery of patient since it is related to chronic&#xD;
      pain, nausea and vomiting and longer hospital stay, generating higher cost to the health&#xD;
      system. Thus, the use of new methods to control postoperative pain is recommended and&#xD;
      multimodal analgesia, an opioid-sparing strategies, has been widely used by several&#xD;
      researchers. Studies show that gabapentins have beneficial effects on postoperative pain&#xD;
      control when used as pre-anesthetic medication, also showing a reduction in opioid&#xD;
      consumption, with few adverse effects. Among gynecological surgeries, abdominal hysterectomy&#xD;
      is one of the procedures that generates the highest degree of acute postoperative pain. Thus,&#xD;
      the aim of the present study is to investigate the effect of oral pregabalin (300 mg) two&#xD;
      hours before abdominal hysterectomy procedures on postoperative pain. This study is a&#xD;
      randomized, double-blind, placebo controlled clinical trial. Patients submitted to abdominal&#xD;
      hysterectomy for benign pathologies will be selected and divided into two groups: the placebo&#xD;
      controlled group (P0) and the pregabalin 300 mg group (P1). Group P0 will receive a placebo&#xD;
      tablet one hour before the procedure, while group P1 will receive a 300 mg tablet of&#xD;
      pregabalin identical to the placebo tablet. The reduction of postoperative pain and the best&#xD;
      quality of patient recovery will be evaluated using the Visual Analogue Pain Scale (VAS) and&#xD;
      the McGill Pain Questionnaire. Also, it will be evaluated the consumption of opioids as a&#xD;
      rescue analgesic medication and the presence of adverse effects such as nausea and vomiting.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The sample population of this study is 102 female patients (50 already included in the&#xD;
      study), who have undergone abdominal hysterectomy surgery for benign conditions, with or&#xD;
      without joint oophorectomy / salpingectomy. The patients received spinal anesthesia, at&#xD;
      hospital &quot;Santa Casa de Alfenas&quot; - Minas Gerais / Brazil (&quot;Casa de Caridade Nossa Senhora do&#xD;
      Perpétuo Socorro&quot;). All surgeries were performed by the same team of surgeons.&#xD;
&#xD;
      All patients were evaluated and followed from the preoperative period, up to 24 hours&#xD;
      postoperatively, passing through the intraoperative period. During all stages, patients were&#xD;
      assisted by a properly trained multi-professional team, consisting of a doctor, nurse and&#xD;
      nursing technician.&#xD;
&#xD;
      For the patient to be included in the study, she must have understood and agreed with the&#xD;
      informed consent form that was explained in detail to all possible candidates in the&#xD;
      preoperative period.&#xD;
&#xD;
      This is a double blind randomized study. The patients were randomly allocated to 02 groups,&#xD;
      in which Group 1 received medication A (designated in the study as medication 1), whereas&#xD;
      Group 2 received medication B (designated in the study as medication 2).&#xD;
&#xD;
      Study participants and researchers were blinded as to the use of drug / placebo to avoid&#xD;
      measurement bias. To carry out the blinding process, an external researcher was assigned to&#xD;
      randomize the groups and prepare the pills in opaque and closed envelopes characterized only&#xD;
      by a control identification (A or B), which is known only to this researcher. Patients in&#xD;
      both groups received identical sealed envelopes, 02h before the start of the anesthetic&#xD;
      procedure, only identified as medication A or B, which contained two pills in each envelope.&#xD;
      A second researcher is responsible for collecting data and monitoring the patient from the&#xD;
      intraoperative period up to 24 hours after discharge from the post-anesthetic recovery room&#xD;
      (PARR).&#xD;
&#xD;
      In the operating room, venoclysis was performed with jelco No. 18 or No. 20, and an infusion&#xD;
      of 08 ml.kg-1 of crystalloid solution (lactated ringer). The patients were properly monitored&#xD;
      with pulse oximetry, cardioscope, and non-invasive blood pressure monitor. After monitoring,&#xD;
      patients were premedicated with intravenous (IV) midazolam at a dosage of 0.03 mg.kg1.&#xD;
&#xD;
      To perform spinal anesthesia, the patients were seated on the surgical stretcher by the&#xD;
      nursing team. Asepsis and antisepsis were performed at the puncture site with alcoholic&#xD;
      chlorhexidine solution. After placement of sterile drapes, local anesthesia was performed&#xD;
      with 2.0% lidocaine without vasoconstrictor. The first attempt at subarachnoid puncture was&#xD;
      performed, using the median technique, between the intervertebral levels L3-L4 or L4-L5 or&#xD;
      L5-S1, with a 25 gauge Quincke needle for subarachnoid anesthesia. If there was a technical&#xD;
      difficulty in the puncture, the paramedian puncture technique was chosen. The confirmation of&#xD;
      the correct puncture was based on the aspiration of cerebrospinal fluid. Anesthesia was&#xD;
      performed with the local anesthetic 0.5% bupivacaine at a dosage of 0.3 mg.kg-1, injected&#xD;
      from a 5 ml disposable syringe. After anesthesia, the patients were placed in the supine&#xD;
      position, and the correct level of anesthesia was proven with thermal sensitivity tests using&#xD;
      cotton soaked with alcoholic solution. After the anesthesia reached the sensory level of the&#xD;
      T4 thoracic vertebra, the surgical team was allowed to start the procedure. Prior to the&#xD;
      beginning of the surgical incision, a delayed bladder probe was performed in all patients&#xD;
      according to the surgeon's indication.&#xD;
&#xD;
      Hemodynamic changes in blood pressure were controlled with the use of vasoactive medications&#xD;
      such as ephedrine or metaraminol. For prophylaxis of postoperative nausea and vomiting (PONV)&#xD;
      ondansetron was administered at a dosage of 4 mg intravenously (IV) 30 minutes before the end&#xD;
      of surgery. Tenoxicam was prescribed for all patients at a dosage of 20 mg IV at regular&#xD;
      intervals every 12 hours for the purpose of anti-inflammatory and analgesic action. For&#xD;
      analgesic relief, dipyrone IV was also prescribed at a dosage of 50 mg.kg-1 at regular&#xD;
      intervals every 6 hours. During the surgery, and also at the end of the surgery, the patients&#xD;
      were evaluated for the degree of sedation using the Ramsay sedation scale as a basis.&#xD;
&#xD;
      At the end of the surgery, the patients were referred to the post-anaesthesia care unit,&#xD;
      where they were monitored again, and went through the pain assessment process using the&#xD;
      visual analog scale (VAS) in relation to pain at rest and &quot;movement&quot; (the patient was asked&#xD;
      to perform the forced cough movement), through a direct question with scale demonstration.&#xD;
      Pains characterized as mild (0 - 2 VAS) received no medication other than those already&#xD;
      prescribed; pain characterized as moderate (3 - 7 EVA) received IV morphine at a dosage of&#xD;
      0.025 mg.kg-1; and severe pain (8 - 10 VAS) received IV morphine at a dose of 0.05 mg.kg-1&#xD;
      every 01 h until analgesic control.&#xD;
&#xD;
      To consider themselves able to be discharged from the post-anaesthesia care unit for clinical&#xD;
      follow-up in wards, patients should reach a score ≥ 9 on the modified Aldrete Scale and have&#xD;
      VAS pain scores ≤ 2.&#xD;
&#xD;
      In the infirmary, patients were tested at regular intervals for pain intensity, by of a team&#xD;
      of nurses trained and qualified to do so. The patients had pain classified as moderate (VAS ≥&#xD;
      2 &lt;8) or severe (VAS ≥ 8), receiving drugs with morphine IV in the dose of 1 mg and 2 mg&#xD;
      respectively, according to the medical prescription.&#xD;
&#xD;
      24 h after discharge from the post-anaesthesia care unit, in the ward, all the patient was&#xD;
      assessed by the same examiner who performed an assessment at the post-anaesthesia care unit,&#xD;
      who stratified the patient again from the EVA and assessed using the McGill questionnaire.&#xD;
&#xD;
      During the entire hospitalization period, the use of central nervous system (CNS) depressant&#xD;
      drugs (example: ketamine, droperidol, promethazine) and / or analgesic drugs that do not&#xD;
      contain any study protocol was avoided. If some patients were medicated with these drugs,&#xD;
      they were excluded from the study.&#xD;
&#xD;
      The data related to surgery (pre, trans and postoperative) were collected for statistical&#xD;
      analysis, according to Annex II, in which a total duration of surgery in minutes; the total&#xD;
      intravenous medication infused; the values of mean arterial pressure and heart rate in the&#xD;
      pre, intra and postoperative period; a presence or not, as well as a quantity, of PONV in the&#xD;
      post-anaesthesia care unit and after 24h; presence or not of dizziness as a possible side&#xD;
      effect; among others.&#xD;
&#xD;
      All data selected through the study will be digitized and analyzed using the Statistic® 7.0&#xD;
      software. The data will be compared using repeated measures ANOVA, followed by Newman-Keuls&#xD;
      post-hoc, being considered for p &lt;0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to an atypical health scenario caused by the COVID-19 pandemic&#xD;
  </why_stopped>
  <start_date type="Actual">September 2, 2019</start_date>
  <completion_date type="Actual">September 30, 2020</completion_date>
  <primary_completion_date type="Actual">September 9, 2020</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>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Postoperative Pain in Rest Assessed 24 Hours After Abdominal Hysterectomy Surgery Using the Visual Analog Scale (VAS)</measure>
    <time_frame>End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)</time_frame>
    <description>Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single dose of pregabalin 300mg or placebo as preemptive analgesia, using the visual analog scale (VAS) consisting of a 10 cm (cm) line ) graduated in natural number intervals, starting at 0 (zero) until reaching 10 (ten), associated with the numbers, drawings related to the pain presented by the patient at the moment, in which the absence of pain (0 ) there is a happy face, and as the numerical value increases, the drawn face will represent the intensity of pain, up to the value of 10, where a face with crying characteristics is found, indicating greater pain.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Postoperative Pain Assessed 24 Hours After Abdominal Hysterectomy Surgery, Using the McGill Pain Questionnaire</measure>
    <time_frame>End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)</time_frame>
    <description>Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single 300mg dose of pregabalin or placebo as preemptive analgesia, using the McGill pain questionnaire, which consists of 20 word groups , and each group can contain from 2 to 6 descriptive words, these descriptors are placed in an increasing order of magnitude in relation to the intensity. The left of each word has a numerical value in an attempt to represent the intensity of the descriptor. For the analysis of the answers, the total number of words chosen in each subgroup by the patient was used to qualify his pain, the minimum value being equal to 0 (zero), if the patient chose not to choose any descriptor, and the maximum value would be 20, as the patient can choose only one descriptor for each subgroup. The quantitative pain index was also evaluated, which represents the sum of the values of each descriptor chosen by the patient, with a minimum value of 0 and a maximum of 78.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Postoperative Pain in Active Movement Assessed 24 Hours After Abdominal Hysterectomy Surgery Using the Visual Analog Scale (VAS)</measure>
    <time_frame>End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)</time_frame>
    <description>Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single dose of pregabalin 300mg or placebo as preemptive analgesia, using the visual analog scale (VAS) consisting of a 10 cm (cm) line ) graduated in natural number intervals, starting at 0 (zero) until reaching 10 (ten), associated with the numbers, drawings related to the pain presented by the patient at the moment, in which the absence of pain (0 ) there is a happy face, and as the numerical value increases, the drawn face will represent the intensity of pain, up to the value of 10, where a face with crying characteristics is found, indicating greater pain.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Doses of Opioids Used as Analgesic Rescue in the Postoperative Period</measure>
    <time_frame>End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)</time_frame>
    <description>Evaluation of the number of intravenous opioid doses used within 24 hours of postoperative abdominal hysterectomy surgery in patients who used pregabalin 300mg or not as preemptive analgesia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time Required for the Use of the First Dose of Opioid as an Analgesic Rescue in the Postoperative Period</measure>
    <time_frame>End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)</time_frame>
    <description>• Evaluation of the time between the end of abdominal hysterectomy surgery and the patient's request for the use of the first dose of intravenous opioid as an analgesic rescue, comparing between patients who used or not pregabalin 300mg as preemptive analgesia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Dizziness Between the Intervention and Control Groups</measure>
    <time_frame>End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery) and also immediately in the post-anesthetic recovery room</time_frame>
    <description>• Assess the presence of adverse effects such as nausea and vomiting, itching and dizziness, comparing the intervention group that used pregabalin with the placebo group</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>Pain, Postoperative</condition>
  <condition>Analgesia</condition>
  <condition>Gabapentin Adverse Reaction</condition>
  <condition>Opioid Abuse</condition>
  <arm_group>
    <arm_group_label>Group P(0) - Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients were randomly allocated to Group P(0) - Placebo by a double blind randomized study. Group P(0) received two placebo tablets as medication, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group P(1) - Pregabalin 300mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients were randomly allocated to Group P(1) - Pregabalin 300mg by a double blind randomized study. Group P(1) received two tablets of pregabalin 150mg, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pregabalin 300mg</intervention_name>
    <description>Group P1 will receive a 300 mg tablet of pregabalin, 02h before the surgical procedure</description>
    <arm_group_label>Group P(1) - Pregabalin 300mg</arm_group_label>
    <other_name>Preemptive analgesia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Group P0 will receive a placebo tablet, 02h before the surgical procedure</description>
    <arm_group_label>Group P(0) - Placebo</arm_group_label>
    <other_name>Controls</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients who will undergo elective abdominal hysterectomy surgery due to benign&#xD;
             pathologies;&#xD;
&#xD;
          2. Be classified as physical status by the Society of Anesthesiologists (ASA) as ASA I&#xD;
             (healthy individual) or ASA II (patient with mild and controlled systemic disease);&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Allergy or intolerance previously known to pregabalin or opioids;&#xD;
&#xD;
          2. Patients with chronic pain or fibromyalgia;&#xD;
&#xD;
          3. Patients on chronic opioid use;&#xD;
&#xD;
          4. Carriers of malignant neoplasms;&#xD;
&#xD;
          5. Pregnant women;&#xD;
&#xD;
          6. People with active uncontrolled cardiovascular disease;&#xD;
&#xD;
          7. Patients with kidney and / or liver disease;&#xD;
&#xD;
          8. Patients who have spinal deformities that make spinal anesthesia impossible;&#xD;
&#xD;
          9. Presence of coagulation disorders or anticoagulant therapy that cannot be suspended&#xD;
             for surgery;&#xD;
&#xD;
         10. Presence of active sepsis.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Female patients</gender_description>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Larissa H Torres, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universidade Federal de Alfenas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Fabrício G Silva, BSc</last_name>
    <role>Study Chair</role>
    <affiliation>Santa Casa de Alfenas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Carlos M de Barros, BSc</last_name>
    <role>Study Chair</role>
    <affiliation>Universidade Federal de Alfenas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marcia H Podestá, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Universidade Federal de Alfenas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Carla S Ceron, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Universidade Federal de Alfenas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Thayná C Silva, BSc</last_name>
    <role>Study Chair</role>
    <affiliation>Santa Casa de Alfenas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Denismar A Nogueira, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Universidade Federal de Alfenas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Tiago M Reis, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Universidade Federal de Alfenas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Milena C Espósito, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Universidade Federal de Alfenas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Danielle A Oliveira, BSc</last_name>
    <role>Study Chair</role>
    <affiliation>Universidade Federal de Alfenas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universidade Federal de Alfenas</name>
      <address>
        <city>Alfenas</city>
        <state>Minas Gerais</state>
        <zip>37130-001</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>Hu J, Huang D, Li M, Wu C, Zhang J. Effects of a single dose of preoperative pregabalin and gabapentin for acute postoperative pain: a network meta-analysis of randomized controlled trials. J Pain Res. 2018 Nov 2;11:2633-2643. doi: 10.2147/JPR.S170810. eCollection 2018.</citation>
    <PMID>30519075</PMID>
  </reference>
  <reference>
    <citation>As-Sanie S, Till SR, Mowers EL, Lim CS, Skinner BD, Fritsch L, Tsodikov A, Dalton VK, Clauw DJ, Brummett CM. Opioid Prescribing Patterns, Patient Use, and Postoperative Pain After Hysterectomy for Benign Indications. Obstet Gynecol. 2017 Dec;130(6):1261-1268. doi: 10.1097/AOG.0000000000002344.</citation>
    <PMID>29112660</PMID>
  </reference>
  <reference>
    <citation>Farzi F, Naderi Nabi B, Mirmansouri A, Fakoor F, Atrkar Roshan Z, Biazar G, Zarei T. Postoperative Pain After Abdominal Hysterectomy: A Randomized, Double-Blind, Controlled Trial Comparing the Effects of Tramadol and Gabapentin as Premedication. Anesth Pain Med. 2016 Jan 17;6(1):e32360. doi: 10.5812/aapm.32360. eCollection 2016 Feb.</citation>
    <PMID>27110531</PMID>
  </reference>
  <reference>
    <citation>Ghai A, Gupta M, Hooda S, Singla D, Wadhera R. A randomized controlled trial to compare pregabalin with gabapentin for postoperative pain in abdominal hysterectomy. Saudi J Anaesth. 2011 Jul;5(3):252-7. doi: 10.4103/1658-354X.84097.</citation>
    <PMID>21957402</PMID>
  </reference>
  <reference>
    <citation>Kohli M, Murali T, Gupta R, Khan P, Bogra J. Optimization of subarachanoid block by oral pregabalin for hysterectomy. J Anaesthesiol Clin Pharmacol. 2011 Jan;27(1):101-5.</citation>
    <PMID>21804717</PMID>
  </reference>
  <reference>
    <citation>Main CJ. Pain assessment in context: a state of the science review of the McGill pain questionnaire 40 years on. Pain. 2016 Jul;157(7):1387-1399. doi: 10.1097/j.pain.0000000000000457.</citation>
    <PMID>26713423</PMID>
  </reference>
  <reference>
    <citation>Steinberg AC, Schimpf MO, White AB, Mathews C, Ellington DR, Jeppson P, Crisp C, Aschkenazi SO, Mamik MM, Balk EM, Murphy M. Preemptive analgesia for postoperative hysterectomy pain control: systematic review and clinical practice guidelines. Am J Obstet Gynecol. 2017 Sep;217(3):303-313.e6. doi: 10.1016/j.ajog.2017.03.013. Epub 2017 Mar 27.</citation>
    <PMID>28351670</PMID>
  </reference>
  <reference>
    <citation>Tulandi T, Krishnamurthy S, Mansour F, Suarthana E, Al-Malki G, Ballesteros LER, Moore A. A Triple-Blind Randomized Trial of Preemptive Use of Gabapentin Before Laparoscopic Hysterectomy for Benign Gynaecologic Conditions. J Obstet Gynaecol Can. 2019 Sep;41(9):1282-1288. doi: 10.1016/j.jogc.2018.11.019. Epub 2019 Jan 25.</citation>
    <PMID>30686609</PMID>
  </reference>
  <reference>
    <citation>Verret M, Lauzier F, Zarychanski R, Savard X, Cossi MJ, Pinard AM, Leblanc G, Turgeon AF. Perioperative use of gabapentinoids for the management of postoperative acute pain: protocol of a systematic review and meta-analysis. Syst Rev. 2019 Jan 16;8(1):24. doi: 10.1186/s13643-018-0906-3.</citation>
    <PMID>30651123</PMID>
  </reference>
  <reference>
    <citation>Yucel A, Ozturk E, Aydogan MS, Durmus M, Colak C, Ersoy MO. Effects of 2 different doses of pregabalin on morphine consumption and pain after abdominal hysterectomy: a randomized, double-blind clinical trial. Curr Ther Res Clin Exp. 2011 Aug;72(4):173-83. doi: 10.1016/j.curtheres.2011.06.004.</citation>
    <PMID>24648587</PMID>
  </reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 24, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <results_first_submitted>January 20, 2021</results_first_submitted>
  <results_first_submitted_qc>February 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 4, 2021</results_first_posted>
  <last_update_submitted>February 11, 2021</last_update_submitted>
  <last_update_submitted_qc>February 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidade Federal de Alfenas</investigator_affiliation>
    <investigator_full_name>Larissa Helena Lobo Torres Pacheco</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>postoperative pain</keyword>
  <keyword>multimodal analgesia</keyword>
  <keyword>pregabalin</keyword>
  <keyword>preemptive analgesia</keyword>
  <keyword>abdominal hysterectomy</keyword>
  <keyword>gabapentins</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Agnosia</mesh_term>
    <mesh_term>Pain, Postoperative</mesh_term>
    <mesh_term>Opioid-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pregabalin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 20, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT04495374/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Group P(0) - Placebo</title>
          <description>Patients were randomly allocated to Group P(0) - Placebo by a double blind randomized study. Group P(0) received two placebo tablets as medication, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Placebo: Group P0 will receive a placebo tablet, 02h before the surgical procedure</description>
        </group>
        <group group_id="P2">
          <title>Group P(1) - Pregabalin 300mg</title>
          <description>Patients were randomly allocated to Group P(1) - Pregabalin 300mg by a double blind randomized study. Group P(1) received two tablets of pregabalin 150mg, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Pregabalin 300mg: Group P1 will receive a 300 mg tablet of pregabalin, 02h before the surgical procedure</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Group P(0) - Placebo</title>
          <description>Patients were randomly allocated to Group P(0) - Placebo by a double blind randomized study. Group P(0) received two placebo tablets as medication, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Placebo: Group P0 will receive a placebo tablet, 02h before the surgical procedure</description>
        </group>
        <group group_id="B2">
          <title>Group P(1) - Pregabalin 300mg</title>
          <description>Patients were randomly allocated to Group P(1) - Pregabalin 300mg by a double blind randomized study. Group P(1) received two tablets of pregabalin 150mg, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Pregabalin 300mg: Group P1 will receive a 300 mg tablet of pregabalin, 02h before the surgical procedure</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="28"/>
            <count group_id="B2" value="27"/>
            <count group_id="B3" value="55"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41.5" spread="7.86"/>
                    <measurement group_id="B2" value="45" spread="4.15"/>
                    <measurement group_id="B3" value="43" spread="6.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Ethnicity</title>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Brown</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Postoperative Pain in Rest Assessed 24 Hours After Abdominal Hysterectomy Surgery Using the Visual Analog Scale (VAS)</title>
        <description>Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single dose of pregabalin 300mg or placebo as preemptive analgesia, using the visual analog scale (VAS) consisting of a 10 cm (cm) line ) graduated in natural number intervals, starting at 0 (zero) until reaching 10 (ten), associated with the numbers, drawings related to the pain presented by the patient at the moment, in which the absence of pain (0 ) there is a happy face, and as the numerical value increases, the drawn face will represent the intensity of pain, up to the value of 10, where a face with crying characteristics is found, indicating greater pain.</description>
        <time_frame>End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group P(0) - Placebo</title>
            <description>Patients were randomly allocated to Group P(0) - Placebo by a double blind randomized study. Group P(0) received two placebo tablets as medication, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Placebo: Group P0 will receive a placebo tablet, 02h before the surgical procedure</description>
          </group>
          <group group_id="O2">
            <title>Group P(1) - Pregabalin 300mg</title>
            <description>Patients were randomly allocated to Group P(1) - Pregabalin 300mg by a double blind randomized study. Group P(1) received two tablets of pregabalin 150mg, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Pregabalin 300mg: Group P1 will receive a 300 mg tablet of pregabalin, 02h before the surgical procedure</description>
          </group>
        </group_list>
        <measure>
          <title>Postoperative Pain in Rest Assessed 24 Hours After Abdominal Hysterectomy Surgery Using the Visual Analog Scale (VAS)</title>
          <description>Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single dose of pregabalin 300mg or placebo as preemptive analgesia, using the visual analog scale (VAS) consisting of a 10 cm (cm) line ) graduated in natural number intervals, starting at 0 (zero) until reaching 10 (ten), associated with the numbers, drawings related to the pain presented by the patient at the moment, in which the absence of pain (0 ) there is a happy face, and as the numerical value increases, the drawn face will represent the intensity of pain, up to the value of 10, where a face with crying characteristics is found, indicating greater pain.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" spread="1.34"/>
                    <measurement group_id="O2" value="2" spread="1.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Postoperative Pain Assessed 24 Hours After Abdominal Hysterectomy Surgery, Using the McGill Pain Questionnaire</title>
        <description>Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single 300mg dose of pregabalin or placebo as preemptive analgesia, using the McGill pain questionnaire, which consists of 20 word groups , and each group can contain from 2 to 6 descriptive words, these descriptors are placed in an increasing order of magnitude in relation to the intensity. The left of each word has a numerical value in an attempt to represent the intensity of the descriptor. For the analysis of the answers, the total number of words chosen in each subgroup by the patient was used to qualify his pain, the minimum value being equal to 0 (zero), if the patient chose not to choose any descriptor, and the maximum value would be 20, as the patient can choose only one descriptor for each subgroup. The quantitative pain index was also evaluated, which represents the sum of the values of each descriptor chosen by the patient, with a minimum value of 0 and a maximum of 78.</description>
        <time_frame>End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group P(0) - Placebo</title>
            <description>Patients were randomly allocated to Group P(0) - Placebo by a double blind randomized study. Group P(0) received two placebo tablets as medication, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Placebo: Group P0 will receive a placebo tablet, 02h before the surgical procedure</description>
          </group>
          <group group_id="O2">
            <title>Group P(1) - Pregabalin 300mg</title>
            <description>Patients were randomly allocated to Group P(1) - Pregabalin 300mg by a double blind randomized study. Group P(1) received two tablets of pregabalin 150mg, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Pregabalin 300mg: Group P1 will receive a 300 mg tablet of pregabalin, 02h before the surgical procedure</description>
          </group>
        </group_list>
        <measure>
          <title>Postoperative Pain Assessed 24 Hours After Abdominal Hysterectomy Surgery, Using the McGill Pain Questionnaire</title>
          <description>Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single 300mg dose of pregabalin or placebo as preemptive analgesia, using the McGill pain questionnaire, which consists of 20 word groups , and each group can contain from 2 to 6 descriptive words, these descriptors are placed in an increasing order of magnitude in relation to the intensity. The left of each word has a numerical value in an attempt to represent the intensity of the descriptor. For the analysis of the answers, the total number of words chosen in each subgroup by the patient was used to qualify his pain, the minimum value being equal to 0 (zero), if the patient chose not to choose any descriptor, and the maximum value would be 20, as the patient can choose only one descriptor for each subgroup. The quantitative pain index was also evaluated, which represents the sum of the values of each descriptor chosen by the patient, with a minimum value of 0 and a maximum of 78.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.5" spread="11"/>
                    <measurement group_id="O2" value="12" spread="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Postoperative Pain in Active Movement Assessed 24 Hours After Abdominal Hysterectomy Surgery Using the Visual Analog Scale (VAS)</title>
        <description>Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single dose of pregabalin 300mg or placebo as preemptive analgesia, using the visual analog scale (VAS) consisting of a 10 cm (cm) line ) graduated in natural number intervals, starting at 0 (zero) until reaching 10 (ten), associated with the numbers, drawings related to the pain presented by the patient at the moment, in which the absence of pain (0 ) there is a happy face, and as the numerical value increases, the drawn face will represent the intensity of pain, up to the value of 10, where a face with crying characteristics is found, indicating greater pain.</description>
        <time_frame>End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group P(0) - Placebo</title>
            <description>Patients were randomly allocated to Group P(0) - Placebo by a double blind randomized study. Group P(0) received two placebo tablets as medication, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Placebo: Group P0 will receive a placebo tablet, 02h before the surgical procedure</description>
          </group>
          <group group_id="O2">
            <title>Group P(1) - Pregabalin 300mg</title>
            <description>Patients were randomly allocated to Group P(1) - Pregabalin 300mg by a double blind randomized study. Group P(1) received two tablets of pregabalin 150mg, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Pregabalin 300mg: Group P1 will receive a 300 mg tablet of pregabalin, 02h before the surgical procedure</description>
          </group>
        </group_list>
        <measure>
          <title>Postoperative Pain in Active Movement Assessed 24 Hours After Abdominal Hysterectomy Surgery Using the Visual Analog Scale (VAS)</title>
          <description>Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single dose of pregabalin 300mg or placebo as preemptive analgesia, using the visual analog scale (VAS) consisting of a 10 cm (cm) line ) graduated in natural number intervals, starting at 0 (zero) until reaching 10 (ten), associated with the numbers, drawings related to the pain presented by the patient at the moment, in which the absence of pain (0 ) there is a happy face, and as the numerical value increases, the drawn face will represent the intensity of pain, up to the value of 10, where a face with crying characteristics is found, indicating greater pain.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" spread="1.41"/>
                    <measurement group_id="O2" value="4" spread="1.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Doses of Opioids Used as Analgesic Rescue in the Postoperative Period</title>
        <description>Evaluation of the number of intravenous opioid doses used within 24 hours of postoperative abdominal hysterectomy surgery in patients who used pregabalin 300mg or not as preemptive analgesia</description>
        <time_frame>End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group P(0) - Placebo</title>
            <description>Patients were randomly allocated to Group P(0) - Placebo by a double blind randomized study. Group P(0) received two placebo tablets as medication, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Placebo: Group P0 will receive a placebo tablet, 02h before the surgical procedure</description>
          </group>
          <group group_id="O2">
            <title>Group P(1) - Pregabalin 300mg</title>
            <description>Patients were randomly allocated to Group P(1) - Pregabalin 300mg by a double blind randomized study. Group P(1) received two tablets of pregabalin 150mg, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Pregabalin 300mg: Group P1 will receive a 300 mg tablet of pregabalin, 02h before the surgical procedure</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Doses of Opioids Used as Analgesic Rescue in the Postoperative Period</title>
          <description>Evaluation of the number of intravenous opioid doses used within 24 hours of postoperative abdominal hysterectomy surgery in patients who used pregabalin 300mg or not as preemptive analgesia</description>
          <units>number of doses</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" spread="1.91"/>
                    <measurement group_id="O2" value="2" spread="1.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time Required for the Use of the First Dose of Opioid as an Analgesic Rescue in the Postoperative Period</title>
        <description>• Evaluation of the time between the end of abdominal hysterectomy surgery and the patient's request for the use of the first dose of intravenous opioid as an analgesic rescue, comparing between patients who used or not pregabalin 300mg as preemptive analgesia</description>
        <time_frame>End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group P(0) - Placebo</title>
            <description>Patients were randomly allocated to Group P(0) - Placebo by a double blind randomized study. Group P(0) received two placebo tablets as medication, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Placebo: Group P0 will receive a placebo tablet, 02h before the surgical procedure</description>
          </group>
          <group group_id="O2">
            <title>Group P(1) - Pregabalin 300mg</title>
            <description>Patients were randomly allocated to Group P(1) - Pregabalin 300mg by a double blind randomized study. Group P(1) received two tablets of pregabalin 150mg, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Pregabalin 300mg: Group P1 will receive a 300 mg tablet of pregabalin, 02h before the surgical procedure</description>
          </group>
        </group_list>
        <measure>
          <title>Time Required for the Use of the First Dose of Opioid as an Analgesic Rescue in the Postoperative Period</title>
          <description>• Evaluation of the time between the end of abdominal hysterectomy surgery and the patient's request for the use of the first dose of intravenous opioid as an analgesic rescue, comparing between patients who used or not pregabalin 300mg as preemptive analgesia</description>
          <units>Time in minutes</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="170" spread="177.6"/>
                    <measurement group_id="O2" value="106" spread="64.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Dizziness Between the Intervention and Control Groups</title>
        <description>• Assess the presence of adverse effects such as nausea and vomiting, itching and dizziness, comparing the intervention group that used pregabalin with the placebo group</description>
        <time_frame>End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery) and also immediately in the post-anesthetic recovery room</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group P(0) - Placebo</title>
            <description>Patients were randomly allocated to Group P(0) - Placebo by a double blind randomized study. Group P(0) received two placebo tablets as medication, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Placebo: Group P0 will receive a placebo tablet, 02h before the surgical procedure</description>
          </group>
          <group group_id="O2">
            <title>Group P(1) - Pregabalin 300mg</title>
            <description>Patients were randomly allocated to Group P(1) - Pregabalin 300mg by a double blind randomized study. Group P(1) received two tablets of pregabalin 150mg, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Pregabalin 300mg: Group P1 will receive a 300 mg tablet of pregabalin, 02h before the surgical procedure</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Dizziness Between the Intervention and Control Groups</title>
          <description>• Assess the presence of adverse effects such as nausea and vomiting, itching and dizziness, comparing the intervention group that used pregabalin with the placebo group</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Data related to adverse events were collected during the follow-up of patients from the preoperative period up to 24h postoperatively.</time_frame>
      <desc>Adverse events such as nausea and vomiting, pruritus, dizziness were evaluated during the entire follow-up of patients</desc>
      <group_list>
        <group group_id="E1">
          <title>Group P(0) - Placebo</title>
          <description>Patients were randomly allocated to Group P(0) - Placebo by a double blind randomized study. Group P(0) received two placebo tablets as medication, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Placebo: Group P0 will receive a placebo tablet, 02h before the surgical procedure</description>
        </group>
        <group group_id="E2">
          <title>Group P(1) - Pregabalin 300mg</title>
          <description>Patients were randomly allocated to Group P(1) - Pregabalin 300mg by a double blind randomized study. Group P(1) received two tablets of pregabalin 150mg, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B&#xD;
Pregabalin 300mg: Group P1 will receive a 300 mg tablet of pregabalin, 02h before the surgical procedure</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>Dizziness</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title vocab="Nausea and vomiting">Nausea and vomiting</sub_title>
                <description>The presence of nausea and vomiting is a common side effect of abdominal surgery, and its incidence may be increased by the use of opioids.</description>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title vocab="Pruritus">Pruritus</sub_title>
                <description>The presence of pruritus is a common adverse event in the use of opioids</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <description>Dizziness is an adverse event that can commonly occur with the use of pregabalin</description>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Failure to monitor patients 24 hours after surgery to assess parameters such as chronic pain and home opioid consumption. All patients admitted to the study underwent abdominal hysterectomy, a surgery known to have higher pain rates, which makes it impossible for the results found to be used as a basis for patients undergoing laparoscopic hysterectomy or other types of surgery.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Profa. Dra. Larissa Helena Lobos Torres Pacheco</name_or_title>
      <organization>Universidade Federal de Alfenas</organization>
      <phone>3537011805 ext 55</phone>
      <email>larissa.torres@unifal-mg.edu.br</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04495374
org study id: 3.334.050
nct id: NCT04495374
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Postoperative pain affects 80% of surgical patients and is one of the main negative symptoms
      resulting from surgery. It impairs the recovery of patient since it is related to chronic
      pain, nausea and vomiting and longer hospital stay, generating higher cost to the health
      system. Thus, the use of new methods to control postoperative pain is recommended and
      multimodal analgesia, an opioid-sparing strategies, has been widely used by several
      researchers. Studies show that gabapentins have beneficial effects on postoperative pain
      control when used as pre-anesthetic medication, also showing a reduction in opioid
      consumption, with few adverse effects. Among gynecological surgeries, abdominal hysterectomy
      is one of the procedures that generates the highest degree of acute postoperative pain. Thus,
      the aim of the present study is to investigate the effect of oral pregabalin (300 mg) two
      hours before abdominal hysterectomy procedures on postoperative pain. This study is a
      randomized, double-blind, placebo controlled clinical trial. Patients submitted to abdominal
      hysterectomy for benign pathologies will be selected and divided into two groups: the placebo
      controlled group (P0) and the pregabalin 300 mg group (P1). Group P0 will receive a placebo
      tablet one hour before the procedure, while group P1 will receive a 300 mg tablet of
      pregabalin identical to the placebo tablet. The reduction of postoperative pain and the best
      quality of patient recovery will be evaluated using the Visual Analogue Pain Scale (VAS) and
      the McGill Pain Questionnaire. Also, it will be evaluated the consumption of opioids as a
      rescue analgesic medication and the presence of adverse effects such as nausea and vomiting.
The sample population of this study is 102 female patients (50 already included in the
      study), who have undergone abdominal hysterectomy surgery for benign conditions, with or
      without joint oophorectomy / salpingectomy. The patients received spinal anesthesia, at
      hospital "Santa Casa de Alfenas" - Minas Gerais / Brazil ("Casa de Caridade Nossa Senhora do
      Perpétuo Socorro"). All surgeries were performed by the same team of surgeons.

      All patients were evaluated and followed from the preoperative period, up to 24 hours
      postoperatively, passing through the intraoperative period. During all stages, patients were
      assisted by a properly trained multi-professional team, consisting of a doctor, nurse and
      nursing technician.

      For the patient to be included in the study, she must have understood and agreed with the
      informed consent form that was explained in detail to all possible candidates in the
      preoperative period.

      This is a double blind randomized study. The patients were randomly allocated to 02 groups,
      in which Group 1 received medication A (designated in the study as medication 1), whereas
      Group 2 received medication B (designated in the study as medication 2).

      Study participants and researchers were blinded as to the use of drug / placebo to avoid
      measurement bias. To carry out the blinding process, an external researcher was assigned to
      randomize the groups and prepare the pills in opaque and closed envelopes characterized only
      by a control identification (A or B), which is known only to this researcher. Patients in
      both groups received identical sealed envelopes, 02h before the start of the anesthetic
      procedure, only identified as medication A or B, which contained two pills in each envelope.
      A second researcher is responsible for collecting data and monitoring the patient from the
      intraoperative period up to 24 hours after discharge from the post-anesthetic recovery room
      (PARR).

      In the operating room, venoclysis was performed with jelco No. 18 or No. 20, and an infusion
      of 08 ml.kg-1 of crystalloid solution (lactated ringer). The patients were properly monitored
      with pulse oximetry, cardioscope, and non-invasive blood pressure monitor. After monitoring,
      patients were premedicated with intravenous (IV) midazolam at a dosage of 0.03 mg.kg1.

      To perform spinal anesthesia, the patients were seated on the surgical stretcher by the
      nursing team. Asepsis and antisepsis were performed at the puncture site with alcoholic
      chlorhexidine solution. After placement of sterile drapes, local anesthesia was performed
      with 2.0% lidocaine without vasoconstrictor. The first attempt at subarachnoid puncture was
      performed, using the median technique, between the intervertebral levels L3-L4 or L4-L5 or
      L5-S1, with a 25 gauge Quincke needle for subarachnoid anesthesia. If there was a technical
      difficulty in the puncture, the paramedian puncture technique was chosen. The confirmation of
      the correct puncture was based on the aspiration of cerebrospinal fluid. Anesthesia was
      performed with the local anesthetic 0.5% bupivacaine at a dosage of 0.3 mg.kg-1, injected
      from a 5 ml disposable syringe. After anesthesia, the patients were placed in the supine
      position, and the correct level of anesthesia was proven with thermal sensitivity tests using
      cotton soaked with alcoholic solution. After the anesthesia reached the sensory level of the
      T4 thoracic vertebra, the surgical team was allowed to start the procedure. Prior to the
      beginning of the surgical incision, a delayed bladder probe was performed in all patients
      according to the surgeon's indication.

      Hemodynamic changes in blood pressure were controlled with the use of vasoactive medications
      such as ephedrine or metaraminol. For prophylaxis of postoperative nausea and vomiting (PONV)
      ondansetron was administered at a dosage of 4 mg intravenously (IV) 30 minutes before the end
      of surgery. Tenoxicam was prescribed for all patients at a dosage of 20 mg IV at regular
      intervals every 12 hours for the purpose of anti-inflammatory and analgesic action. For
      analgesic relief, dipyrone IV was also prescribed at a dosage of 50 mg.kg-1 at regular
      intervals every 6 hours. During the surgery, and also at the end of the surgery, the patients
      were evaluated for the degree of sedation using the Ramsay sedation scale as a basis.

      At the end of the surgery, the patients were referred to the post-anaesthesia care unit,
      where they were monitored again, and went through the pain assessment process using the
      visual analog scale (VAS) in relation to pain at rest and "movement" (the patient was asked
      to perform the forced cough movement), through a direct question with scale demonstration.
      Pains characterized as mild (0 - 2 VAS) received no medication other than those already
      prescribed; pain characterized as moderate (3 - 7 EVA) received IV morphine at a dosage of
      0.025 mg.kg-1; and severe pain (8 - 10 VAS) received IV morphine at a dose of 0.05 mg.kg-1
      every 01 h until analgesic control.

      To consider themselves able to be discharged from the post-anaesthesia care unit for clinical
      follow-up in wards, patients should reach a score ≥ 9 on the modified Aldrete Scale and have
      VAS pain scores ≤ 2.

      In the infirmary, patients were tested at regular intervals for pain intensity, by of a team
      of nurses trained and qualified to do so. The patients had pain classified as moderate (VAS ≥
      2 <8) or severe (VAS ≥ 8), receiving drugs with morphine IV in the dose of 1 mg and 2 mg
      respectively, according to the medical prescription.

      24 h after discharge from the post-anaesthesia care unit, in the ward, all the patient was
      assessed by the same examiner who performed an assessment at the post-anaesthesia care unit,
      who stratified the patient again from the EVA and assessed using the McGill questionnaire.

      During the entire hospitalization period, the use of central nervous system (CNS) depressant
      drugs (example: ketamine, droperidol, promethazine) and / or analgesic drugs that do not
      contain any study protocol was avoided. If some patients were medicated with these drugs,
      they were excluded from the study.

      The data related to surgery (pre, trans and postoperative) were collected for statistical
      analysis, according to Annex II, in which a total duration of surgery in minutes; the total
      intravenous medication infused; the values of mean arterial pressure and heart rate in the
      pre, intra and postoperative period; a presence or not, as well as a quantity, of PONV in the
      post-anaesthesia care unit and after 24h; presence or not of dizziness as a possible side
      effect; among others.

      All data selected through the study will be digitized and analyzed using the Statistic® 7.0
      software. The data will be compared using repeated measures ANOVA, followed by Newman-Keuls
      post-hoc, being considered for p <0.05.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
measure: Postoperative Pain in Rest Assessed 24 Hours After Abdominal Hysterectomy Surgery Using the Visual Analog Scale (VAS)
time frame: End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)
description: Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single dose of pregabalin 300mg or placebo as preemptive analgesia, using the visual analog scale (VAS) consisting of a 10 cm (cm) line ) graduated in natural number intervals, starting at 0 (zero) until reaching 10 (ten), associated with the numbers, drawings related to the pain presented by the patient at the moment, in which the absence of pain (0 ) there is a happy face, and as the numerical value increases, the drawn face will represent the intensity of pain, up to the value of 10, where a face with crying characteristics is found, indicating greater pain.
measure: Postoperative Pain Assessed 24 Hours After Abdominal Hysterectomy Surgery, Using the McGill Pain Questionnaire
time frame: End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)
description: Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single 300mg dose of pregabalin or placebo as preemptive analgesia, using the McGill pain questionnaire, which consists of 20 word groups , and each group can contain from 2 to 6 descriptive words, these descriptors are placed in an increasing order of magnitude in relation to the intensity. The left of each word has a numerical value in an attempt to represent the intensity of the descriptor. For the analysis of the answers, the total number of words chosen in each subgroup by the patient was used to qualify his pain, the minimum value being equal to 0 (zero), if the patient chose not to choose any descriptor, and the maximum value would be 20, as the patient can choose only one descriptor for each subgroup. The quantitative pain index was also evaluated, which represents the sum of the values of each descriptor chosen by the patient, with a minimum value of 0 and a maximum of 78.
measure: Postoperative Pain in Active Movement Assessed 24 Hours After Abdominal Hysterectomy Surgery Using the Visual Analog Scale (VAS)
time frame: End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)
description: Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single dose of pregabalin 300mg or placebo as preemptive analgesia, using the visual analog scale (VAS) consisting of a 10 cm (cm) line ) graduated in natural number intervals, starting at 0 (zero) until reaching 10 (ten), associated with the numbers, drawings related to the pain presented by the patient at the moment, in which the absence of pain (0 ) there is a happy face, and as the numerical value increases, the drawn face will represent the intensity of pain, up to the value of 10, where a face with crying characteristics is found, indicating greater pain.
measure: Number of Doses of Opioids Used as Analgesic Rescue in the Postoperative Period
time frame: End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)
description: Evaluation of the number of intravenous opioid doses used within 24 hours of postoperative abdominal hysterectomy surgery in patients who used pregabalin 300mg or not as preemptive analgesia
measure: Time Required for the Use of the First Dose of Opioid as an Analgesic Rescue in the Postoperative Period
time frame: End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)
description: • Evaluation of the time between the end of abdominal hysterectomy surgery and the patient's request for the use of the first dose of intravenous opioid as an analgesic rescue, comparing between patients who used or not pregabalin 300mg as preemptive analgesia
measure: Number of Participants With Dizziness Between the Intervention and Control Groups
time frame: End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery) and also immediately in the post-anesthetic recovery room
description: • Assess the presence of adverse effects such as nausea and vomiting, itching and dizziness, comparing the intervention group that used pregabalin with the placebo group
arm group label: Group P(0) - Placebo
arm group type: Placebo Comparator
description: Patients were randomly allocated to Group P(0) - Placebo by a double blind randomized study. Group P(0) received two placebo tablets as medication, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B
arm group label: Group P(1) - Pregabalin 300mg
arm group type: Experimental
description: Patients were randomly allocated to Group P(1) - Pregabalin 300mg by a double blind randomized study. Group P(1) received two tablets of pregabalin 150mg, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B
intervention type: Drug
intervention name: Pregabalin 300mg
description: Group P1 will receive a 300 mg tablet of pregabalin, 02h before the surgical procedure
arm group label: Group P(1) - Pregabalin 300mg
other name: Preemptive analgesia
intervention type: Other
intervention name: Placebo
description: Group P0 will receive a placebo tablet, 02h before the surgical procedure
arm group label: Group P(0) - Placebo
other name: Controls
criteria: 
gender: Female
gender based: Yes
gender description: Female patients
minimum age: 20 Years
maximum age: 65 Years
healthy volunteers: No
last name: Larissa H Torres, PhD
role: Principal Investigator
affiliation: Universidade Federal de Alfenas
last name: Fabrício G Silva, BSc
role: Study Chair
affiliation: Santa Casa de Alfenas
last name: Carlos M de Barros, BSc
role: Study Chair
affiliation: Universidade Federal de Alfenas
last name: Marcia H Podestá, PhD
role: Study Chair
affiliation: Universidade Federal de Alfenas
last name: Carla S Ceron, PhD
role: Study Chair
affiliation: Universidade Federal de Alfenas
last name: Thayná C Silva, BSc
role: Study Chair
affiliation: Santa Casa de Alfenas
last name: Denismar A Nogueira, PhD
role: Study Chair
affiliation: Universidade Federal de Alfenas
last name: Tiago M Reis, PhD
role: Study Chair
affiliation: Universidade Federal de Alfenas
last name: Milena C Espósito, PhD
role: Study Chair
affiliation: Universidade Federal de Alfenas
last name: Danielle A Oliveira, BSc
role: Study Chair
affiliation: Universidade Federal de Alfenas
facility: 
country: Brazil
citation: Hu J, Huang D, Li M, Wu C, Zhang J. Effects of a single dose of preoperative pregabalin and gabapentin for acute postoperative pain: a network meta-analysis of randomized controlled trials. J Pain Res. 2018 Nov 2;11:2633-2643. doi: 10.2147/JPR.S170810. eCollection 2018.
PMID: 30519075
citation: As-Sanie S, Till SR, Mowers EL, Lim CS, Skinner BD, Fritsch L, Tsodikov A, Dalton VK, Clauw DJ, Brummett CM. Opioid Prescribing Patterns, Patient Use, and Postoperative Pain After Hysterectomy for Benign Indications. Obstet Gynecol. 2017 Dec;130(6):1261-1268. doi: 10.1097/AOG.0000000000002344.
PMID: 29112660
citation: Farzi F, Naderi Nabi B, Mirmansouri A, Fakoor F, Atrkar Roshan Z, Biazar G, Zarei T. Postoperative Pain After Abdominal Hysterectomy: A Randomized, Double-Blind, Controlled Trial Comparing the Effects of Tramadol and Gabapentin as Premedication. Anesth Pain Med. 2016 Jan 17;6(1):e32360. doi: 10.5812/aapm.32360. eCollection 2016 Feb.
PMID: 27110531
citation: Ghai A, Gupta M, Hooda S, Singla D, Wadhera R. A randomized controlled trial to compare pregabalin with gabapentin for postoperative pain in abdominal hysterectomy. Saudi J Anaesth. 2011 Jul;5(3):252-7. doi: 10.4103/1658-354X.84097.
PMID: 21957402
citation: Kohli M, Murali T, Gupta R, Khan P, Bogra J. Optimization of subarachanoid block by oral pregabalin for hysterectomy. J Anaesthesiol Clin Pharmacol. 2011 Jan;27(1):101-5.
PMID: 21804717
citation: Main CJ. Pain assessment in context: a state of the science review of the McGill pain questionnaire 40 years on. Pain. 2016 Jul;157(7):1387-1399. doi: 10.1097/j.pain.0000000000000457.
PMID: 26713423
citation: Steinberg AC, Schimpf MO, White AB, Mathews C, Ellington DR, Jeppson P, Crisp C, Aschkenazi SO, Mamik MM, Balk EM, Murphy M. Preemptive analgesia for postoperative hysterectomy pain control: systematic review and clinical practice guidelines. Am J Obstet Gynecol. 2017 Sep;217(3):303-313.e6. doi: 10.1016/j.ajog.2017.03.013. Epub 2017 Mar 27.
PMID: 28351670
citation: Tulandi T, Krishnamurthy S, Mansour F, Suarthana E, Al-Malki G, Ballesteros LER, Moore A. A Triple-Blind Randomized Trial of Preemptive Use of Gabapentin Before Laparoscopic Hysterectomy for Benign Gynaecologic Conditions. J Obstet Gynaecol Can. 2019 Sep;41(9):1282-1288. doi: 10.1016/j.jogc.2018.11.019. Epub 2019 Jan 25.
PMID: 30686609
citation: Verret M, Lauzier F, Zarychanski R, Savard X, Cossi MJ, Pinard AM, Leblanc G, Turgeon AF. Perioperative use of gabapentinoids for the management of postoperative acute pain: protocol of a systematic review and meta-analysis. Syst Rev. 2019 Jan 16;8(1):24. doi: 10.1186/s13643-018-0906-3.
PMID: 30651123
citation: Yucel A, Ozturk E, Aydogan MS, Durmus M, Colak C, Ersoy MO. Effects of 2 different doses of pregabalin on morphine consumption and pain after abdominal hysterectomy: a randomized, double-blind clinical trial. Curr Ther Res Clin Exp. 2011 Aug;72(4):173-83. doi: 10.1016/j.curtheres.2011.06.004.
PMID: 24648587
responsible party type: Principal Investigator
investigator affiliation: Universidade Federal de Alfenas
investigator full name: Larissa Helena Lobo Torres Pacheco
investigator title: Principal Investigator
mesh term: Agnosia
mesh term: Pain, Postoperative
mesh term: Opioid-Related Disorders
mesh term: Pregabalin
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Failure to monitor patients 24 hours after surgery to assess parameters such as chronic pain and home opioid consumption. All patients admitted to the study underwent abdominal hysterectomy, a surgery known to have higher pain rates, which makes it impossible for the results found to be used as a basis for patients undergoing laparoscopic hysterectomy or other types of surgery.
point of contact: 