<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/NCT02203175</url>
  </required_header>
  <id_info>
    <org_study_id>100-26.01.2011</org_study_id>
    <nct_id>NCT02203175</nct_id>
  </id_info>
  <brief_title>Prevention of Propofol Injection Pain</brief_title>
  <acronym>VRS</acronym>
  <official_title>The Effect of Fentanyl-propofol Mixture on Propofol Injection Pain.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yeditepe University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yeditepe University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pain on injection of propofol is a comman problem. The investigators planned to evaluate the&#xD;
      effect of propofol-fentanyl mixture on propofol injection pain and compare it with fentanyl&#xD;
      pretreatment and control groups.&#xD;
&#xD;
      Following ethics committee approval, 150 ASA I,II patients (18-65 yr) undergoing general&#xD;
      anesthesia were enrolled to this study. Exclusion criteria were communication difficulty,&#xD;
      psychiatric, neurologic disorders and history of allergy. Patients were randomly assigned to&#xD;
      one of tree equal groups. Before the anesthesia induction, Group C (Control, n=50) and group&#xD;
      M (mixture, n=50) received 5 ml isotonic saline, group F (fentanyl, n=50)received 2micgr/kg&#xD;
      fentanyl. 10 seconds after the study drugs had been given, a standart question about the&#xD;
      comfort of the injection was asked to the patient. The investigators used the verbal rating&#xD;
      scale (VRS) for evaluation of propofol injection pain. Statistical analyses were performed&#xD;
      with Student's t and Fisher's exact tests; p value &lt;0,05 was considered significant.&#xD;
&#xD;
      Demographic data was similar among the groups (table I) In group M, the number of the&#xD;
      patients having propofol injection pain was significantly lower compared to groups F and C&#xD;
      (p&lt;0,001 for both) None of the patients in groups F and M experienced severe pain whereas 24&#xD;
      patients (48%) had severe pain in group C (p&lt;0.001 for both).&#xD;
&#xD;
      This study shown that fentanyl-propofol mixture is more effective compared to both fentanyl&#xD;
      pretreatment and placebo in preventing propofol injection pain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      150 ASA I-II patients, aged 18-65 year and scheduled for elective surgery were enrolled in&#xD;
      the study. Patients were randomly assigned to one of three equal groups using an Excel&#xD;
      (Microsoft , USA) generated randomization table. No patient received premedication. On&#xD;
      arrival at the operation room after monitoring [ECG, noninvasive blood pressure, pulse&#xD;
      oximeter and bispectral index (BIS)], a 20 gauge cannula was inserted into a vein on the&#xD;
      dorsum of the patient's nondominant hand and %0.9 NaCl infusion was started at a rate of 5&#xD;
      ml/kg/h for 5 min, then i.v. infusion was stopped and the arm with the i.v. line was elevated&#xD;
      for 15 s for drainage of venous blood. A tourniquet was placed on the forearm to produce a&#xD;
      venous occlusion for 1 minute. The patients were pretreated by the anesthesiologist blinded&#xD;
      to the groups. Before the anesthesia induction, Group C (Control, n=50) and group M (mixture,&#xD;
      n=50) received 5 ml isotonic saline whereas group F (fentanyl, n=50)received 2micgr/kg&#xD;
      fentanyl diluted with saline at a total volume of 5 ml as a pretreatment. (Propofol 1%&#xD;
      Fresenius-FRESENIUS CABI- Fentanyl 0,05 mg/ml JANSSEN-CILAG ) The drugs were prepared by one&#xD;
      of the investigators blinded to the study groups. Pretreatment solutions were identical in&#xD;
      appearance. pH value of the fentanyl, propofol and fentanyl-propofol mixture was measured at&#xD;
      the laboratory of our university with pH meter. For the patients in Group M a mixture of&#xD;
      propofol and fentanyl was prepared using 20 ml propofol and 4 ml fentanyl. After the&#xD;
      tourniquet was released, patients in Group C and F received 5 ml propofol whereas patients in&#xD;
      Group M received 5 ml of this mixture. 10 seconds after the study drugs had been given, a&#xD;
      standart question about the comfort of the injection was asked to the patient. We used the&#xD;
      verbal rating scale (VRS) for evaluation of propofol injection pain. (0: none (negative&#xD;
      response to questioning), 1: mild pain (pain reported only in response to questioning without&#xD;
      any behavioral signs, 2: moderate pain (pain reported in response to questioning and&#xD;
      accompanied by a behavioral sign or pain reported spontaneously without questioning), 3:&#xD;
      severe pain (strong vocal response or response accompanied by facial grimacing, arm&#xD;
      withdrawal or tears). All patients were able to answer the question about the pain and in all&#xD;
      patients BIS was above 80 at that moment. The remaining dose of propofol and fentanyl was&#xD;
      then given to complete the induction of anesthesia. Complete induction dose was propofol 2&#xD;
      mg/kg and fentanyl 2 mcg/kg. Because Group F and Group M had already received 2 mcg/kg&#xD;
      fentanyl before, only Group C patients received 2mcg/kg fentanyl after the muscle relaxant.&#xD;
      Before the induction of anesthesia, anesthesiologist explained all the patients that they&#xD;
      will receive an iv. anesthetic that might lead to pain on the injection point, hand or arm.&#xD;
&#xD;
      STATISTICAL ANALYSES: Propofol injection pain was the primary outcome in the study. It is&#xD;
      reported that the incidence of propofol injection pain is approximately 70 % and to decrease&#xD;
      this incidence to 35% , it is calculated that 49 patients were needed in each group with a&#xD;
      type I error of 0.05 and power of 90% . Due to possible drop outs in all groups 50 patients&#xD;
      were taken into the study. Demographic data were compared with Student's t test . Fisher's&#xD;
      Exact test and x2 tests were used to assess differences between categorical variables. A p&#xD;
      value &lt; 0.05 was considered significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2011</start_date>
  <completion_date type="Actual">April 2012</completion_date>
  <primary_completion_date type="Actual">April 2012</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>complete response</measure>
    <time_frame>1 year</time_frame>
    <description>The primary outcome is complete response: A complete response is defined as no pain during proposal injection.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Group C (plasebo): no pretreatment</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>saline injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>propofol and fentanyl</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>propofol 50 mg with fentanyl 50 mcgr iv during anesthesia induction ones time</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>saline</intervention_name>
    <description>Before the anesthesia induction, 5 ml isotonic saline</description>
    <arm_group_label>Group C (plasebo): no pretreatment</arm_group_label>
    <other_name>serum phisyologic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>fentanyl</intervention_name>
    <description>before the anesthesia induction 50 mcgr fentanyl</description>
    <arm_group_label>Group C (plasebo): no pretreatment</arm_group_label>
    <arm_group_label>propofol and fentanyl</arm_group_label>
    <other_name>talinat</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>propofol</intervention_name>
    <description>during anesthesia 50 mg proposal with 50 mcgr fentanyl</description>
    <arm_group_label>Group C (plasebo): no pretreatment</arm_group_label>
    <arm_group_label>propofol and fentanyl</arm_group_label>
    <other_name>pofol</other_name>
    <other_name>diprivan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18-65 age&#xD;
&#xD;
          -  ASA status I-II&#xD;
&#xD;
          -  Scheduled for elective surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Communication difficulty&#xD;
&#xD;
          -  Psychiatric and neurolojic disorders&#xD;
&#xD;
          -  History of allergy to the study drugs&#xD;
&#xD;
          -  Use of analgesics or sedative drugs within 24 hours before surgery.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>ferdi menda, assoc. prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yeditepe University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yeditepe University Hospital</name>
      <address>
        <city>Istanbul</city>
        <state>Devlet Yolu, Ankara cad 102/104, Kozyatagi</state>
        <zip>34752</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>June 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <last_update_submitted>September 23, 2014</last_update_submitted>
  <last_update_submitted_qc>September 23, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 25, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Yeditepe University Hospital</investigator_affiliation>
    <investigator_full_name>nurcan kizilcik</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>propofol</keyword>
  <keyword>pretreatment</keyword>
  <keyword>mixture</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Propofol</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/NCT02203175
org study id: 100-26.01.2011
nct id: NCT02203175
lead sponsor: 
has dmc: No
Pain on injection of propofol is a comman problem. The investigators planned to evaluate the
      effect of propofol-fentanyl mixture on propofol injection pain and compare it with fentanyl
      pretreatment and control groups.

      Following ethics committee approval, 150 ASA I,II patients (18-65 yr) undergoing general
      anesthesia were enrolled to this study. Exclusion criteria were communication difficulty,
      psychiatric, neurologic disorders and history of allergy. Patients were randomly assigned to
      one of tree equal groups. Before the anesthesia induction, Group C (Control, n=50) and group
      M (mixture, n=50) received 5 ml isotonic saline, group F (fentanyl, n=50)received 2micgr/kg
      fentanyl. 10 seconds after the study drugs had been given, a standart question about the
      comfort of the injection was asked to the patient. The investigators used the verbal rating
      scale (VRS) for evaluation of propofol injection pain. Statistical analyses were performed
      with Student's t and Fisher's exact tests; p value <0,05 was considered significant.

      Demographic data was similar among the groups (table I) In group M, the number of the
      patients having propofol injection pain was significantly lower compared to groups F and C
      (p<0,001 for both) None of the patients in groups F and M experienced severe pain whereas 24
      patients (48%) had severe pain in group C (p<0.001 for both).

      This study shown that fentanyl-propofol mixture is more effective compared to both fentanyl
      pretreatment and placebo in preventing propofol injection pain.
150 ASA I-II patients, aged 18-65 year and scheduled for elective surgery were enrolled in
      the study. Patients were randomly assigned to one of three equal groups using an Excel
      (Microsoft , USA) generated randomization table. No patient received premedication. On
      arrival at the operation room after monitoring [ECG, noninvasive blood pressure, pulse
      oximeter and bispectral index (BIS)], a 20 gauge cannula was inserted into a vein on the
      dorsum of the patient's nondominant hand and %0.9 NaCl infusion was started at a rate of 5
      ml/kg/h for 5 min, then i.v. infusion was stopped and the arm with the i.v. line was elevated
      for 15 s for drainage of venous blood. A tourniquet was placed on the forearm to produce a
      venous occlusion for 1 minute. The patients were pretreated by the anesthesiologist blinded
      to the groups. Before the anesthesia induction, Group C (Control, n=50) and group M (mixture,
      n=50) received 5 ml isotonic saline whereas group F (fentanyl, n=50)received 2micgr/kg
      fentanyl diluted with saline at a total volume of 5 ml as a pretreatment. (Propofol 1%
      Fresenius-FRESENIUS CABI- Fentanyl 0,05 mg/ml JANSSEN-CILAG ) The drugs were prepared by one
      of the investigators blinded to the study groups. Pretreatment solutions were identical in
      appearance. pH value of the fentanyl, propofol and fentanyl-propofol mixture was measured at
      the laboratory of our university with pH meter. For the patients in Group M a mixture of
      propofol and fentanyl was prepared using 20 ml propofol and 4 ml fentanyl. After the
      tourniquet was released, patients in Group C and F received 5 ml propofol whereas patients in
      Group M received 5 ml of this mixture. 10 seconds after the study drugs had been given, a
      standart question about the comfort of the injection was asked to the patient. We used the
      verbal rating scale (VRS) for evaluation of propofol injection pain. (0: none (negative
      response to questioning), 1: mild pain (pain reported only in response to questioning without
      any behavioral signs, 2: moderate pain (pain reported in response to questioning and
      accompanied by a behavioral sign or pain reported spontaneously without questioning), 3:
      severe pain (strong vocal response or response accompanied by facial grimacing, arm
      withdrawal or tears). All patients were able to answer the question about the pain and in all
      patients BIS was above 80 at that moment. The remaining dose of propofol and fentanyl was
      then given to complete the induction of anesthesia. Complete induction dose was propofol 2
      mg/kg and fentanyl 2 mcg/kg. Because Group F and Group M had already received 2 mcg/kg
      fentanyl before, only Group C patients received 2mcg/kg fentanyl after the muscle relaxant.
      Before the induction of anesthesia, anesthesiologist explained all the patients that they
      will receive an iv. anesthetic that might lead to pain on the injection point, hand or arm.

      STATISTICAL ANALYSES: Propofol injection pain was the primary outcome in the study. It is
      reported that the incidence of propofol injection pain is approximately 70 % and to decrease
      this incidence to 35% , it is calculated that 49 patients were needed in each group with a
      type I error of 0.05 and power of 90% . Due to possible drop outs in all groups 50 patients
      were taken into the study. Demographic data were compared with Student's t test . Fisher's
      Exact test and x2 tests were used to assess differences between categorical variables. A p
      value < 0.05 was considered significant.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Prevention
masking: Double (Investigator, Outcomes Assessor)
measure: complete response
time frame: 1 year
description: The primary outcome is complete response: A complete response is defined as no pain during proposal injection.
arm group label: Group C (plasebo): no pretreatment
arm group type: Placebo Comparator
description: saline injection
arm group label: propofol and fentanyl
arm group type: Active Comparator
description: propofol 50 mg with fentanyl 50 mcgr iv during anesthesia induction ones time
intervention type: Drug
intervention name: saline
description: Before the anesthesia induction, 5 ml isotonic saline
arm group label: Group C (plasebo): no pretreatment
other name: serum phisyologic
intervention type: Drug
intervention name: fentanyl
description: before the anesthesia induction 50 mcgr fentanyl
arm group label: Group C (plasebo): no pretreatment
arm group label: propofol and fentanyl
other name: talinat
intervention type: Drug
intervention name: propofol
description: during anesthesia 50 mg proposal with 50 mcgr fentanyl
arm group label: Group C (plasebo): no pretreatment
arm group label: propofol and fentanyl
other name: pofol
other name: diprivan
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: ferdi menda, assoc. prof.
role: Principal Investigator
affiliation: Yeditepe University
facility: 
country: Turkey
responsible party type: Principal Investigator
investigator affiliation: Yeditepe University Hospital
investigator full name: nurcan kizilcik
investigator title: MD
mesh term: Fentanyl
mesh term: Propofol