<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/NCT02248493</url>
  </required_header>
  <id_info>
    <org_study_id>BEC-MF-10</org_study_id>
    <nct_id>NCT02248493</nct_id>
  </id_info>
  <brief_title>Intravenous Paracetamol for Postoperative Pain</brief_title>
  <acronym>IVPARACET</acronym>
  <official_title>The Effect of Intravenous Paracetamol in Combination With NSAIDs for Postoperative Pain in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lithuanian University of Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lithuanian University of Health Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to define if intravenous paracetamol may improve analgesia and&#xD;
      outcome in pediatric surgical patients treated with non-steroidal anti-inflammatory drugs&#xD;
      (NSAIDs) postoperatively.&#xD;
&#xD;
      Hypothesis: intravenous paracetamol in a dose 60 mg/kg/24 h IV, given in addition to IV&#xD;
      ketoprofen (4,5 mg/kg/24h), improves analgesia and physical recovery in children and&#xD;
      adolescents following surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients aged 1-18 years undergoing general, plastic or orthopedic surgery with expected&#xD;
      moderate to severe pain at least for 24 hours postoperatively, who meet inclusion criteria&#xD;
      and does not meet exclusion criteria, are enrolled. At the end of surgical procedure, at skin&#xD;
      closure, all patients are given 1,5 mg/kg intravenous ketoprofen and repeated every 8 hours&#xD;
      up till 4,5 mg/kg/24 h. Patients in paracetamol group are additionally given the first dose&#xD;
      of IV paracetamol 20 mg/kg and repeated 6 and 20 hours postoperatively up till 60 mg/kg/24 h.&#xD;
      Patients in the placebo group are given 0.9% sodium chloride 2 ml/kg IV and repeated 6 and 20&#xD;
      hours postoperatively.&#xD;
&#xD;
      After surgery optional rescue analgesia is given on patient request: either tramadol in a&#xD;
      dose of 2 mg/kg (up till 4 mg/kg/24h), either patient-controlled analgesia (PCA) with&#xD;
      morphine, as indicated according to the standard of care. Patients are evaluated up till 24&#xD;
      hours postoperatively. After that patients are followed up as long as indicated per standard&#xD;
      of care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">March 2017</completion_date>
  <primary_completion_date type="Actual">March 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>change in postoperative intravenous opioid dose</measure>
    <time_frame>24 hours postoperatively</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>change in pain level (analgesia) assessed by 10 point pain scales</measure>
    <time_frame>1 hour postoperatively</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in pain level (analgesia) assessed by 10 point pain scales</measure>
    <time_frame>24 hours postoperatively</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>time until the first oral intake after surgery</measure>
    <time_frame>24 hours postoperatively</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>time until the first urination after surgery</measure>
    <time_frame>24 hours postoperatively</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>time until ambulation after surgery</measure>
    <time_frame>24 hours postoperatively</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Pain, Postoperative</condition>
  <condition>Recovery of Function</condition>
  <condition>Child</condition>
  <arm_group>
    <arm_group_label>paracetamol and ketoprofen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>paracetamol 20 mg/kg (1% 2 ml/kg) IV at the end of surgery 6 and 20 hours thereafter.&#xD;
ketoprofen 1.5 mg/kg IV at the end of surgery 8 and 16 hours thereafter. tramadol 2 mg/kg IV on patient request up til 4 mg/kg or PCA morphine during 24 hours postoperatively.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo and ketoprofen</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>0.9% sodium chloride (2 ml/kg) IV at the end of surgery 6 and 20 hours thereafter.&#xD;
ketoprofen 1.5 mg/kg IV at the end of surgery 8 and 16 hours thereafter. tramadol 2 mg/kg IV on patient request up til 4 mg/kg or PCA morphine during 24 hours postoperatively.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paracetamol</intervention_name>
    <arm_group_label>paracetamol and ketoprofen</arm_group_label>
    <other_name>Acetaminophen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (for paracetamol)</intervention_name>
    <arm_group_label>placebo and ketoprofen</arm_group_label>
    <other_name>0.9% sodium cloride solution</other_name>
    <other_name>Normal saline solution</other_name>
    <other_name>Izotonic saline solution</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketoprofen</intervention_name>
    <arm_group_label>paracetamol and ketoprofen</arm_group_label>
    <arm_group_label>placebo and ketoprofen</arm_group_label>
    <other_name>Ketonal</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tramadol</intervention_name>
    <description>Administered on request as rescue medication in a dose 2 mg/kg IV up till 2 doses. No other opioid is given to these patients.</description>
    <arm_group_label>paracetamol and ketoprofen</arm_group_label>
    <arm_group_label>placebo and ketoprofen</arm_group_label>
    <other_name>Tramal</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <description>administered in patients receiving IV PCA with morphine postoperatively. No other opioid is given to these patients.</description>
    <arm_group_label>paracetamol and ketoprofen</arm_group_label>
    <arm_group_label>placebo and ketoprofen</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients 1-18 years of age, undergoing general, plastic or orthopedic surgery with&#xD;
             expected median to severe pain postoperatively.&#xD;
&#xD;
          -  physical status of the patient corresponding to American Society of Anesthesiologists&#xD;
             (ASA) class 1 or 2&#xD;
&#xD;
          -  Signed written informed consent by parents/official caregivers.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy to paracetamol, ketoprofen, tramadol, morphine or any NSAID&#xD;
&#xD;
          -  oncologic disease&#xD;
&#xD;
          -  central nervous system disease&#xD;
&#xD;
          -  renal dysfunction&#xD;
&#xD;
          -  hepatic dysfunction&#xD;
&#xD;
          -  bronchial asthma&#xD;
&#xD;
          -  ulcer(s) in gastrointestinal system&#xD;
&#xD;
          -  hemorrhagic diathesis&#xD;
&#xD;
          -  chronic use of NSAIDs&#xD;
&#xD;
          -  chronic use of opioids&#xD;
&#xD;
          -  chronic use of anticoagulants&#xD;
&#xD;
          -  female patient is known to be pregnant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Danguole C Rugyte, MD. PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lithuanian University of Health Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Lithuanian University of Health Sciences Kaunas Clinics</name>
      <address>
        <city>Kaunas</city>
        <zip>50009</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Lithuania</country>
  </location_countries>
  <reference>
    <citation>Ong CK, Seymour RA, Lirk P, Merry AF. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg. 2010 Apr 1;110(4):1170-9. doi: 10.1213/ANE.0b013e3181cf9281. Epub 2010 Feb 8.</citation>
    <PMID>20142348</PMID>
  </reference>
  <reference>
    <citation>Wong I, St John-Green C, Walker SM. Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Paediatr Anaesth. 2013 Jun;23(6):475-95. doi: 10.1111/pan.12163. Epub 2013 Apr 9.</citation>
    <PMID>23570544</PMID>
  </reference>
  <reference>
    <citation>Hiller A, Silvanto M, Savolainen S, Tarkkila P. Propacetamol and diclofenac alone and in combination for analgesia after elective tonsillectomy. Acta Anaesthesiol Scand. 2004 Oct;48(9):1185-9. doi: 10.1111/j.1399-6576.2004.00473.x.</citation>
    <PMID>15352967</PMID>
  </reference>
  <reference>
    <citation>Rugyte D, Kokki H. Intravenous ketoprofen as an adjunct to patient-controlled analgesia morphine in adolescents with thoracic surgery: a placebo controlled double-blinded study. Eur J Pain. 2007 Aug;11(6):694-9. doi: 10.1016/j.ejpain.2006.11.001. Epub 2006 Dec 20.</citation>
    <PMID>17185016</PMID>
  </reference>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>September 22, 2014</study_first_submitted>
  <study_first_submitted_qc>September 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>March 3, 2017</last_update_submitted>
  <last_update_submitted_qc>March 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Lithuanian University of Health Sciences</investigator_affiliation>
    <investigator_full_name>Danguole C Rugyte</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Pain, Postoperative</keyword>
  <keyword>Paracetamol</keyword>
  <keyword>Administration, Intravenous</keyword>
  <keyword>Anti-Inflammatory Agents, Non-Steroidal</keyword>
  <keyword>Child</keyword>
  <keyword>Adolescent</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</mesh_term>
    <mesh_term>Ketoprofen</mesh_term>
    <mesh_term>Morphine</mesh_term>
    <mesh_term>Tramadol</mesh_term>
    <mesh_term>Pharmaceutical Solutions</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02248493
org study id: BEC-MF-10
nct id: NCT02248493
lead sponsor: 
has dmc: No
The purpose of this study is to define if intravenous paracetamol may improve analgesia and
      outcome in pediatric surgical patients treated with non-steroidal anti-inflammatory drugs
      (NSAIDs) postoperatively.

      Hypothesis: intravenous paracetamol in a dose 60 mg/kg/24 h IV, given in addition to IV
      ketoprofen (4,5 mg/kg/24h), improves analgesia and physical recovery in children and
      adolescents following surgery.
Patients aged 1-18 years undergoing general, plastic or orthopedic surgery with expected
      moderate to severe pain at least for 24 hours postoperatively, who meet inclusion criteria
      and does not meet exclusion criteria, are enrolled. At the end of surgical procedure, at skin
      closure, all patients are given 1,5 mg/kg intravenous ketoprofen and repeated every 8 hours
      up till 4,5 mg/kg/24 h. Patients in paracetamol group are additionally given the first dose
      of IV paracetamol 20 mg/kg and repeated 6 and 20 hours postoperatively up till 60 mg/kg/24 h.
      Patients in the placebo group are given 0.9% sodium chloride 2 ml/kg IV and repeated 6 and 20
      hours postoperatively.

      After surgery optional rescue analgesia is given on patient request: either tramadol in a
      dose of 2 mg/kg (up till 4 mg/kg/24h), either patient-controlled analgesia (PCA) with
      morphine, as indicated according to the standard of care. Patients are evaluated up till 24
      hours postoperatively. After that patients are followed up as long as indicated per standard
      of care.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: change in postoperative intravenous opioid dose
time frame: 24 hours postoperatively
measure: change in pain level (analgesia) assessed by 10 point pain scales
time frame: 1 hour postoperatively
measure: change in pain level (analgesia) assessed by 10 point pain scales
time frame: 24 hours postoperatively
measure: time until the first oral intake after surgery
time frame: 24 hours postoperatively
measure: time until the first urination after surgery
time frame: 24 hours postoperatively
measure: time until ambulation after surgery
time frame: 24 hours postoperatively
arm group label: paracetamol and ketoprofen
arm group type: Experimental
description: paracetamol 20 mg/kg (1% 2 ml/kg) IV at the end of surgery 6 and 20 hours thereafter.
ketoprofen 1.5 mg/kg IV at the end of surgery 8 and 16 hours thereafter. tramadol 2 mg/kg IV on patient request up til 4 mg/kg or PCA morphine during 24 hours postoperatively.
arm group label: placebo and ketoprofen
arm group type: Placebo Comparator
description: 0.9% sodium chloride (2 ml/kg) IV at the end of surgery 6 and 20 hours thereafter.
ketoprofen 1.5 mg/kg IV at the end of surgery 8 and 16 hours thereafter. tramadol 2 mg/kg IV on patient request up til 4 mg/kg or PCA morphine during 24 hours postoperatively.
intervention type: Drug
intervention name: Paracetamol
arm group label: paracetamol and ketoprofen
other name: Acetaminophen
intervention type: Drug
intervention name: Placebo (for paracetamol)
arm group label: placebo and ketoprofen
other name: 0.9% sodium cloride solution
other name: Normal saline solution
other name: Izotonic saline solution
intervention type: Drug
intervention name: Ketoprofen
arm group label: paracetamol and ketoprofen
arm group label: placebo and ketoprofen
other name: Ketonal
intervention type: Drug
intervention name: Tramadol
description: Administered on request as rescue medication in a dose 2 mg/kg IV up till 2 doses. No other opioid is given to these patients.
arm group label: paracetamol and ketoprofen
arm group label: placebo and ketoprofen
other name: Tramal
intervention type: Drug
intervention name: Morphine
description: administered in patients receiving IV PCA with morphine postoperatively. No other opioid is given to these patients.
arm group label: paracetamol and ketoprofen
arm group label: placebo and ketoprofen
criteria: 
gender: All
minimum age: 1 Year
maximum age: 18 Years
healthy volunteers: No
last name: Danguole C Rugyte, MD. PhD
role: Principal Investigator
affiliation: Lithuanian University of Health Sciences
facility: 
country: Lithuania
citation: Ong CK, Seymour RA, Lirk P, Merry AF. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg. 2010 Apr 1;110(4):1170-9. doi: 10.1213/ANE.0b013e3181cf9281. Epub 2010 Feb 8.
PMID: 20142348
citation: Wong I, St John-Green C, Walker SM. Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Paediatr Anaesth. 2013 Jun;23(6):475-95. doi: 10.1111/pan.12163. Epub 2013 Apr 9.
PMID: 23570544
citation: Hiller A, Silvanto M, Savolainen S, Tarkkila P. Propacetamol and diclofenac alone and in combination for analgesia after elective tonsillectomy. Acta Anaesthesiol Scand. 2004 Oct;48(9):1185-9. doi: 10.1111/j.1399-6576.2004.00473.x.
PMID: 15352967
citation: Rugyte D, Kokki H. Intravenous ketoprofen as an adjunct to patient-controlled analgesia morphine in adolescents with thoracic surgery: a placebo controlled double-blinded study. Eur J Pain. 2007 Aug;11(6):694-9. doi: 10.1016/j.ejpain.2006.11.001. Epub 2006 Dec 20.
PMID: 17185016
responsible party type: Principal Investigator
investigator affiliation: Lithuanian University of Health Sciences
investigator full name: Danguole C Rugyte
investigator title: MD, PhD
mesh term: Pain, Postoperative
mesh term: Acetaminophen
mesh term: Ketoprofen
mesh term: Morphine
mesh term: Tramadol
mesh term: Pharmaceutical Solutions