<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/NCT02254525</url>
  </required_header>
  <id_info>
    <org_study_id>BIBEC02</org_study_id>
    <nct_id>NCT02254525</nct_id>
  </id_info>
  <brief_title>A Multicenter Trial of the Efficacy and Safety of a New Formulation of Ibuprofen 800 mg Every 6 Hours in the Management of Postoperative Pain</brief_title>
  <official_title>A Multicenter, Randomized, Double-blind, and Parallel Groups, Placebo-controlled Trial of the Efficacy and Safety of a New Formulation of Ibuprofen 800 mg Every 6 Hours in the Management of Postoperative Pain.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biomendi S.A.U.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pivotal S.L.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Biomendi S.A.U.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to study the efficacy of intravenous administration of ibuprofen&#xD;
      compared to placebo in patients with postoperative pain and evaluate its tolerability and&#xD;
      safety profile.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase III, national, multicenter, randomized, double-blind, parallel groups, and&#xD;
      placebo-controlled.&#xD;
&#xD;
      Patients will be randomized to receive either ibuprofen or placebo. Stratified randomization&#xD;
      will be used to assign eligible patients to a stratum according to type of surgery and&#xD;
      centre. Randomization sequence will be generated in the coordinating centre.&#xD;
&#xD;
      Blinding of the patient and study personnel evaluating response will be warranted by adequate&#xD;
      drug labelling.&#xD;
&#xD;
      All patients will receive morphine administered by patient controlled analgesia (PCA)&#xD;
      following a similar schedule in all centres: 1 mg bolus dose with a close time of 5 min and a&#xD;
      maximum of 10 mg in an hour and a maximum of 30 mg in 4 hours.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sample not reached in traumathology arm&#xD;
  </why_stopped>
  <start_date>May 2012</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluate the efficacy of intravenous ibuprofen for the management of postoperative pain in comparison to placebo</measure>
    <time_frame>First 24 hours post- surgery</time_frame>
    <description>The primary efficacy endpoint will be the reduction in total morphine use in the first 24 hours post- surgery as compared to placebo.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary efficacy endpoints</measure>
    <time_frame>From 0 hours to 72 hours post- surgery</time_frame>
    <description>- Consumption of morphine in the first 48 h (and 72) hours post- surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary efficacy endpoints</measure>
    <time_frame>From 0 hours to 72 hours post- surgery</time_frame>
    <description>- Pain intensity at rest and with movement measured with the eleven points visual analogue scale (VAS), at 1 and 3 hours and every 6 hours thereafter up to hour 24 h, and then every 8 h up to 6 hour after the last ibuprofen dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary efficacy endpoints</measure>
    <time_frame>From 0 hours to 72 hours post- surgery</time_frame>
    <description>- Ramsay-Hunt sedation scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary efficacy endpoints</measure>
    <time_frame>From 0 hours to 72 hours post- surgery</time_frame>
    <description>- Time to first subsequent narcotic analgesia (or time to treatment failure).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary efficacy endpoints</measure>
    <time_frame>From 0 hours to 72 hours post- surgery</time_frame>
    <description>- Number of doses of morphine and number of attempts of dosing at PCA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary tolerability and safety endpoints</measure>
    <time_frame>From 0 hours to 72 hours post- surgery</time_frame>
    <description>- Report of adverse events (AEs) during the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary tolerability and safety endpoints</measure>
    <time_frame>From 0 hours to 72 hours post- surgery</time_frame>
    <description>- Local reactions due to IV infusion (pain, erythema, phlebitis)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary tolerability and safety endpoints</measure>
    <time_frame>From 0 hours to 72 hours post- surgery</time_frame>
    <description>- Vital signs (heart rate, blood pressure, temperature) at 1, 3, 6 hour after the initial dose and every 8 hours thereafter.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary tolerability and safety endpoints</measure>
    <time_frame>From 0 hours to 72 hours post- surgery</time_frame>
    <description>- Routine laboratory tests (chemistry, haematology and coagulation) at baseline and within 24 hours after the last dose.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">231</enrollment>
  <condition>Postoperative Pain</condition>
  <arm_group>
    <arm_group_label>800 mg intravenous ibuprofen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment group: 800 mg IV ibuprofen, starting at the moment of skin closure and every 6 hours, infused over 15 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>200 ml of saline solution</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo group: 200 ml of saline solution, starting at the moment of skin closure and every 6 hours, infused over 15 min.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravenous ibuprofen</intervention_name>
    <description>Treatment group: 800 mg IV ibuprofen, starting at the moment of skin closure and every 6 hours up to 72 hours after the first dose.&#xD;
All patients will receive morphine administered by patient controlled analgesia (PCA). Investigation treatment will be administered every 6 hours until 24 h in abdominal surgery, 48 h in hip surgery and 72 h in knee surgery.</description>
    <arm_group_label>800 mg intravenous ibuprofen</arm_group_label>
    <other_name>IV ibuprofen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline solution</intervention_name>
    <description>Placebo group: 200 ml of saline solution, starting at the moment of skin closure and every 6 hours up to 72 hours after the first dose.&#xD;
All patients will receive morphine administered by patient controlled analgesia (PCA). Investigation treatment will be administered every 6 hours until 24 h in abdominal surgery, 48 h in hip surgery and 72 h in knee surgery.</description>
    <arm_group_label>200 ml of saline solution</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men or women between 18 and 80 years old.&#xD;
&#xD;
          2. Being scheduled for elective single surgical site orthopaedic surgery (hip or knee&#xD;
             joint replacement, corsed ligaments, column or shoulder surgery), or abdominal surgery&#xD;
             (inguinal hernia, cholecystectomy, eventration or hiatus hernia)&#xD;
&#xD;
          3. Being scheduled for general anaesthesia or regional anesthesia without regional&#xD;
             analgesia after surgery.&#xD;
&#xD;
          4. Having anticipated need for postoperative narcotic analgesia administered by patient&#xD;
             controlled analgesia (PCA).&#xD;
&#xD;
          5. Expected to stay at the hospital for at least 24 h.&#xD;
&#xD;
          6. Providing written informed consent for participating in this study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of NSAID within 12 hours prior to the first planned dose.&#xD;
&#xD;
          2. Taking oral anticoagulants, lithium, combination of ACE inhibitors, furosemide or&#xD;
             aspirin.&#xD;
&#xD;
          3. Anaemia (haemoglobin &lt;10 g/dl) and/or history or evidence of asthma or heart failure.&#xD;
&#xD;
          4. History of allergy or hypersensitivity to any component of IV ibuprofen, aspirin or&#xD;
             aspirin related products, NSAID or COX-2 inhibitors.&#xD;
&#xD;
          5. Pregnant or nursing.&#xD;
&#xD;
          6. Weight less than 40 kg.&#xD;
&#xD;
          7. History of severe head trauma that required hospitalization, intracranial surgery or&#xD;
             stroke within the previous 30 days, or any history of intracerebral arteriovenous&#xD;
             malformation, cerebral aneurism or CNS mass lesion.&#xD;
&#xD;
          8. History of congenital bleeding diathesis or any active clinically significant bleeding&#xD;
             or underlying platelet dysfunction.&#xD;
&#xD;
          9. Gastrointestinal bleeding that required medical intervention.&#xD;
&#xD;
         10. Platelet count less than 80.000 determined within the 28 days prior to surgery.&#xD;
&#xD;
         11. Pre-existing dependence on narcotics or receiving chronic treatment with opioids.&#xD;
&#xD;
         12. Severe renal failure (calculated creatinine clearance &lt; 60 ml/min).&#xD;
&#xD;
         13. Liver failure, ALAT or ASAT &gt;3 times upper limit of normality, or bilirubin &gt;2 g/dl.&#xD;
&#xD;
         14. Diagnosed of Bowel Inflammatory Disease.&#xD;
&#xD;
         15. Not able to understand the requirements of the study, or to abide by the study&#xD;
             restrictions or to return for the required assessments.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Concepción Pérez, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital La Princesa</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Francisco Abad, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital La Princesa</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dolores Ochoa, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital La Princesa</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Antonio Planas, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital La Princesa</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital de Móstoles</name>
      <address>
        <city>Móstoles</city>
        <state>Madrid</state>
        <zip>28935</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Xeral Cíes de Vigo</name>
      <address>
        <city>Vigo</city>
        <state>Pontevedra</state>
        <zip>15781</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Cruces</name>
      <address>
        <city>Barakaldo</city>
        <state>Vizcaya</state>
        <zip>48903</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario de A Coruña</name>
      <address>
        <city>La Coruña</city>
        <zip>15001</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Arnau de Vilanova de Lleida</name>
      <address>
        <city>Lleida</city>
        <zip>25198</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital La Princesa</name>
      <address>
        <city>Madrid</city>
        <zip>28006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundación Jiménez Díaz</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Montepríncipe</name>
      <address>
        <city>Madrid</city>
        <zip>28660</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clínica Universitaria de Navarra</name>
      <address>
        <city>Pamplona</city>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen de la Salud</name>
      <address>
        <city>Toledo</city>
        <zip>45005</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital La Fe</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico de Valladolid</name>
      <address>
        <city>Valladolid</city>
        <zip>47005</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 25, 2014</study_first_submitted>
  <study_first_submitted_qc>October 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2014</study_first_posted>
  <last_update_submitted>October 1, 2014</last_update_submitted>
  <last_update_submitted_qc>October 1, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 2, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Ibuprofen</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/NCT02254525
org study id: BIBEC02
nct id: NCT02254525
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to study the efficacy of intravenous administration of ibuprofen
      compared to placebo in patients with postoperative pain and evaluate its tolerability and
      safety profile.
This is a phase III, national, multicenter, randomized, double-blind, parallel groups, and
      placebo-controlled.

      Patients will be randomized to receive either ibuprofen or placebo. Stratified randomization
      will be used to assign eligible patients to a stratum according to type of surgery and
      centre. Randomization sequence will be generated in the coordinating centre.

      Blinding of the patient and study personnel evaluating response will be warranted by adequate
      drug labelling.

      All patients will receive morphine administered by patient controlled analgesia (PCA)
      following a similar schedule in all centres: 1 mg bolus dose with a close time of 5 min and a
      maximum of 10 mg in an hour and a maximum of 30 mg in 4 hours.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Evaluate the efficacy of intravenous ibuprofen for the management of postoperative pain in comparison to placebo
time frame: First 24 hours post- surgery
description: The primary efficacy endpoint will be the reduction in total morphine use in the first 24 hours post- surgery as compared to placebo.
measure: Secondary efficacy endpoints
time frame: From 0 hours to 72 hours post- surgery
description: - Consumption of morphine in the first 48 h (and 72) hours post- surgery.
measure: Secondary efficacy endpoints
time frame: From 0 hours to 72 hours post- surgery
description: - Pain intensity at rest and with movement measured with the eleven points visual analogue scale (VAS), at 1 and 3 hours and every 6 hours thereafter up to hour 24 h, and then every 8 h up to 6 hour after the last ibuprofen dose.
measure: Secondary efficacy endpoints
time frame: From 0 hours to 72 hours post- surgery
description: - Ramsay-Hunt sedation scale.
measure: Secondary efficacy endpoints
time frame: From 0 hours to 72 hours post- surgery
description: - Time to first subsequent narcotic analgesia (or time to treatment failure).
measure: Secondary efficacy endpoints
time frame: From 0 hours to 72 hours post- surgery
description: - Number of doses of morphine and number of attempts of dosing at PCA
measure: Secondary tolerability and safety endpoints
time frame: From 0 hours to 72 hours post- surgery
description: - Report of adverse events (AEs) during the study
measure: Secondary tolerability and safety endpoints
time frame: From 0 hours to 72 hours post- surgery
description: - Local reactions due to IV infusion (pain, erythema, phlebitis)
measure: Secondary tolerability and safety endpoints
time frame: From 0 hours to 72 hours post- surgery
description: - Vital signs (heart rate, blood pressure, temperature) at 1, 3, 6 hour after the initial dose and every 8 hours thereafter.
measure: Secondary tolerability and safety endpoints
time frame: From 0 hours to 72 hours post- surgery
description: - Routine laboratory tests (chemistry, haematology and coagulation) at baseline and within 24 hours after the last dose.
arm group label: 800 mg intravenous ibuprofen
arm group type: Experimental
description: Treatment group: 800 mg IV ibuprofen, starting at the moment of skin closure and every 6 hours, infused over 15 minutes.
arm group label: 200 ml of saline solution
arm group type: Placebo Comparator
description: Placebo group: 200 ml of saline solution, starting at the moment of skin closure and every 6 hours, infused over 15 min.
intervention type: Drug
intervention name: Intravenous ibuprofen
description: Treatment group: 800 mg IV ibuprofen, starting at the moment of skin closure and every 6 hours up to 72 hours after the first dose.
All patients will receive morphine administered by patient controlled analgesia (PCA). Investigation treatment will be administered every 6 hours until 24 h in abdominal surgery, 48 h in hip surgery and 72 h in knee surgery.
arm group label: 800 mg intravenous ibuprofen
other name: IV ibuprofen
intervention type: Drug
intervention name: Saline solution
description: Placebo group: 200 ml of saline solution, starting at the moment of skin closure and every 6 hours up to 72 hours after the first dose.
All patients will receive morphine administered by patient controlled analgesia (PCA). Investigation treatment will be administered every 6 hours until 24 h in abdominal surgery, 48 h in hip surgery and 72 h in knee surgery.
arm group label: 200 ml of saline solution
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Concepción Pérez, MD
role: Study Chair
affiliation: Hospital La Princesa
last name: Francisco Abad, MD
role: Study Chair
affiliation: Hospital La Princesa
last name: Dolores Ochoa, MD
role: Study Chair
affiliation: Hospital La Princesa
last name: Antonio Planas, MD
role: Study Chair
affiliation: Hospital La Princesa
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Pain, Postoperative
mesh term: Ibuprofen