<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/NCT02187614</url>
  </required_header>
  <id_info>
    <org_study_id>IRB Number: 14-00059</org_study_id>
    <secondary_id>Hamad Medical Corporation-MRC</secondary_id>
    <nct_id>NCT02187614</nct_id>
  </id_info>
  <brief_title>Efficacy Study of Different Analgesic Options in Kidney Stone Pain Management</brief_title>
  <official_title>A Double Blind, Multi-arm Randomized Control Trial, for Efficacy of Intramuscular Diclofenac Versus Intravenous Morphine Versus Intravenous Paracetamol, in Renal Colic Emergency Department Pain Management</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hamad Medical Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hamad Medical Corporation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Abdominal pain is one of the most common presentations to an emergency department (ED). Among&#xD;
      patients presenting with abdominal pain, a common diagnosis in the Middle East is renal colic&#xD;
      (urolithiasis or Kidney stones). As the patients with renal colic writhe around in agonizing&#xD;
      pain, the first priority in an ED from a patient's perspective is fast and safe analgesia and&#xD;
      to be pain free as early as possible. There are variations in physician preference to choose&#xD;
      initial analgesic drug for managing such pain. Commonly used drugs are:&#xD;
&#xD;
        -  Opioids such as Morphine or Fentanyl&#xD;
&#xD;
        -  Non steroidal drugs such as Diclofenac, Ketorolac or Brufen&#xD;
&#xD;
        -  and Paracetamol intravenous injection.&#xD;
&#xD;
      A robust evidence in comparison of diclofenac versus morphine and paracetamol is lacking.&#xD;
      This study is design to obtain data on efficacy of these three drugs within 30 minutes in a&#xD;
      non inferiority trail.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a double blind RCT, where participants will be enrolled consecutively after&#xD;
      meeting eligibility criteria and obtaining a written informed consent. They will be assign to&#xD;
      one of the three study arms by computer generated randomization process. The study packets&#xD;
      will be prepared by a dedicated nurse or pharmacist who will not a part of investigating&#xD;
      team. Each Patients will receive one analgesic drug (active drug) and two placebos. Drugs&#xD;
      will be given as one intramuscular injection and two intravenous solutions.&#xD;
&#xD;
      Pain score will be recorded using NRS at 0, 30, 60, and 90 minutes. Data will be collected on&#xD;
      standard Data collection form. Each participant will receive analgesia from study packet&#xD;
      which contains, one active drug and two placebos to be administer as one intramuscular and&#xD;
      two intravenous solutions. At any given time every patient will receive one analgesia from&#xD;
      either Diclofenac, Paracetamol or Morphine. If patient pain does not respond to initial&#xD;
      treatments, at 30 minutes a rescue analgesia in form of morphine will be administered till&#xD;
      patient is pain free or NRS&lt;=2 or adverse event to morphine.&#xD;
&#xD;
      Based on the results of previous studies (1-3), proportion of patients achieving more than&#xD;
      50% pain reduction, is between 65-75% for diclofenac, morphine and paracetamol when compared&#xD;
      with other drugs. In each group, 437 patients are required to detect a difference of 10% in&#xD;
      primary outcome, in a superiority trial with power (1-beta) of 90% and significance level&#xD;
      (alpha) of 5% in this study. Considering 15% extra, total sample size required in this&#xD;
      superiority trial will be 1507 patients in total.&#xD;
&#xD;
      Data will be collected on a standard data recording form and it will be converted to&#xD;
      electronic excel sheet hiding patient identifiable details. Continuous variables will be&#xD;
      presented as mean with standard deviation (SD). Categorical variables will be calculated as&#xD;
      proportions and presented with 95% Confidence interval (CI). Statistical analyses will be&#xD;
      undertaken using Stata 12.0 (College Station, Texas).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The proportion of patients achieving a reduction of &gt;50% on Numerical Rating Scale (NRS-11) from the initial NRS recorded at the end of 30 minutes in each study arm.</measure>
    <time_frame>at 30 minutes after analgesia</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>reduction in mean NRS</measure>
    <time_frame>at 30, 60 and 90 minutes after analgesia</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>adverse event rate</measure>
    <time_frame>Within 14 days of ED visit</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>total analgesia requirement to get pain score (NRS) less than or equal to 2.</measure>
    <time_frame>by 90 minutes</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">1645</enrollment>
  <condition>Renal Colic</condition>
  <condition>Urinary Calculi</condition>
  <arm_group>
    <arm_group_label>Diclofenac and Placebos</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this group will receive a Diclofenac 75 mg intramuscular injection, and two placebo saline solutions intravenously.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Morphine and Placebos</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in this group will receive Morphine 0.1 mg/kg intravenously, along with an additional intravenous placebo and an intramuscular placebo injection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Paracetamol and Placebos</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>participants in this group will receive intravenous Paracetamol 1 gm solution, along with an additional intravenous placebo and an intramuscular placebo injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Diclofenac</intervention_name>
    <arm_group_label>Diclofenac and Placebos</arm_group_label>
    <other_name>Voltaren</other_name>
    <other_name>Diclofen</other_name>
    <other_name>Diclorex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <arm_group_label>Morphine and Placebos</arm_group_label>
    <other_name>Morphine sulphate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paracetamol</intervention_name>
    <arm_group_label>Paracetamol and Placebos</arm_group_label>
    <other_name>Perfalgan</other_name>
    <other_name>Acetaminophen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <arm_group_label>Diclofenac and Placebos</arm_group_label>
    <arm_group_label>Morphine and Placebos</arm_group_label>
    <arm_group_label>Paracetamol and Placebos</arm_group_label>
    <other_name>saline solution</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;=18 years and &lt; 65 years&#xD;
&#xD;
          -  Acute onset, one side flank or loin pain, with or without radiation to groin or&#xD;
             genital areas.&#xD;
&#xD;
          -  Pain intensity on NRS more than or equal to 4. (Moderate to Severe Pain)&#xD;
&#xD;
          -  Diagnosis confirmed by non contrast CT KUB within the ED visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Traumatic flank pain&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Known renal failure or impairment&#xD;
&#xD;
          -  Known allergy to morphine, diclofenac or paracetamol&#xD;
&#xD;
          -  Bronchial asthma&#xD;
&#xD;
          -  Previously enrolled in the study.&#xD;
&#xD;
          -  Use of any analgesia in last 6 hour.&#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>Dr.Sameer A. Pathan, MBBS, MCEM</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hamad Medical Corporation</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Prof. Peter A Cameron, MD,FACEM</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hamad Medical Corporation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emergency Department, Hamad General Hospital.</name>
      <address>
        <city>Doha</city>
        <zip>3050</zip>
        <country>Qatar</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Qatar</country>
  </location_countries>
  <reference>
    <citation>Grissa MH, Claessens YE, Bouida W, Boubaker H, Boudhib L, Kerkeni W, Boukef R, Nouira S. Paracetamol vs piroxicam to relieve pain in renal colic. Results of a randomized controlled trial. Am J Emerg Med. 2011 Feb;29(2):203-6. doi: 10.1016/j.ajem.2009.09.019. Epub 2010 Oct 8.</citation>
    <PMID>20934829</PMID>
  </reference>
  <reference>
    <citation>Behzadnia MJ, Javadzadeh HR, Saboori F. Time of admission, gender and age: challenging factors in emergency renal colic - a preliminary study. Trauma Mon. 2012 Fall;17(3):329-32. doi: 10.5812/traumamon.6800. Epub 2012 Oct 10.</citation>
    <PMID>24350118</PMID>
  </reference>
  <reference>
    <citation>Shaden Salameh; Nurit Hiller; Meir Antopolsky; Fedaa Ghanem; Yigaal Abramovitz; Ruth Stalnikowics. Diclofenac versus Tramadol in the Treatment of Renal Colic: A Prospective, Randomized Trial. The Open Emergency Medicine Journal. 2011; 4: 9-13.</citation>
  </reference>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <last_update_submitted>March 17, 2015</last_update_submitted>
  <last_update_submitted_qc>March 17, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 18, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hamad Medical Corporation</investigator_affiliation>
    <investigator_full_name>Dr. SAMEER PATHAN</investigator_full_name>
    <investigator_title>Research Fellow and Specialist</investigator_title>
  </responsible_party>
  <keyword>Acute Renal colic</keyword>
  <keyword>Acute Ureteric Colic</keyword>
  <keyword>Renal or Ureteral Calculi</keyword>
  <keyword>Urolithiasis</keyword>
  <keyword>Kidney or Ureteral stones</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urinary Calculi</mesh_term>
    <mesh_term>Urolithiasis</mesh_term>
    <mesh_term>Colic</mesh_term>
    <mesh_term>Calculi</mesh_term>
    <mesh_term>Renal Colic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</mesh_term>
    <mesh_term>Diclofenac</mesh_term>
    <mesh_term>Morphine</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/NCT02187614
org study id: IRB Number: 14-00059
secondary id: Hamad Medical Corporation-MRC
nct id: NCT02187614
lead sponsor: 
has dmc: No
Abdominal pain is one of the most common presentations to an emergency department (ED). Among
      patients presenting with abdominal pain, a common diagnosis in the Middle East is renal colic
      (urolithiasis or Kidney stones). As the patients with renal colic writhe around in agonizing
      pain, the first priority in an ED from a patient's perspective is fast and safe analgesia and
      to be pain free as early as possible. There are variations in physician preference to choose
      initial analgesic drug for managing such pain. Commonly used drugs are:

        -  Opioids such as Morphine or Fentanyl

        -  Non steroidal drugs such as Diclofenac, Ketorolac or Brufen

        -  and Paracetamol intravenous injection.

      A robust evidence in comparison of diclofenac versus morphine and paracetamol is lacking.
      This study is design to obtain data on efficacy of these three drugs within 30 minutes in a
      non inferiority trail.
This will be a double blind RCT, where participants will be enrolled consecutively after
      meeting eligibility criteria and obtaining a written informed consent. They will be assign to
      one of the three study arms by computer generated randomization process. The study packets
      will be prepared by a dedicated nurse or pharmacist who will not a part of investigating
      team. Each Patients will receive one analgesic drug (active drug) and two placebos. Drugs
      will be given as one intramuscular injection and two intravenous solutions.

      Pain score will be recorded using NRS at 0, 30, 60, and 90 minutes. Data will be collected on
      standard Data collection form. Each participant will receive analgesia from study packet
      which contains, one active drug and two placebos to be administer as one intramuscular and
      two intravenous solutions. At any given time every patient will receive one analgesia from
      either Diclofenac, Paracetamol or Morphine. If patient pain does not respond to initial
      treatments, at 30 minutes a rescue analgesia in form of morphine will be administered till
      patient is pain free or NRS<=2 or adverse event to morphine.

      Based on the results of previous studies (1-3), proportion of patients achieving more than
      50% pain reduction, is between 65-75% for diclofenac, morphine and paracetamol when compared
      with other drugs. In each group, 437 patients are required to detect a difference of 10% in
      primary outcome, in a superiority trial with power (1-beta) of 90% and significance level
      (alpha) of 5% in this study. Considering 15% extra, total sample size required in this
      superiority trial will be 1507 patients in total.

      Data will be collected on a standard data recording form and it will be converted to
      electronic excel sheet hiding patient identifiable details. Continuous variables will be
      presented as mean with standard deviation (SD). Categorical variables will be calculated as
      proportions and presented with 95% Confidence interval (CI). Statistical analyses will be
      undertaken using Stata 12.0 (College Station, Texas).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The proportion of patients achieving a reduction of >50% on Numerical Rating Scale (NRS-11) from the initial NRS recorded at the end of 30 minutes in each study arm.
time frame: at 30 minutes after analgesia
measure: reduction in mean NRS
time frame: at 30, 60 and 90 minutes after analgesia
measure: adverse event rate
time frame: Within 14 days of ED visit
measure: total analgesia requirement to get pain score (NRS) less than or equal to 2.
time frame: by 90 minutes
arm group label: Diclofenac and Placebos
arm group type: Experimental
description: Participants in this group will receive a Diclofenac 75 mg intramuscular injection, and two placebo saline solutions intravenously.
arm group label: Morphine and Placebos
arm group type: Active Comparator
description: Participants in this group will receive Morphine 0.1 mg/kg intravenously, along with an additional intravenous placebo and an intramuscular placebo injection.
arm group label: Paracetamol and Placebos
arm group type: Active Comparator
description: participants in this group will receive intravenous Paracetamol 1 gm solution, along with an additional intravenous placebo and an intramuscular placebo injection.
intervention type: Drug
intervention name: Diclofenac
arm group label: Diclofenac and Placebos
other name: Voltaren
other name: Diclofen
other name: Diclorex
intervention type: Drug
intervention name: Morphine
arm group label: Morphine and Placebos
other name: Morphine sulphate
intervention type: Drug
intervention name: Paracetamol
arm group label: Paracetamol and Placebos
other name: Perfalgan
other name: Acetaminophen
intervention type: Drug
intervention name: Placebos
arm group label: Diclofenac and Placebos
arm group label: Morphine and Placebos
arm group label: Paracetamol and Placebos
other name: saline solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Dr.Sameer A. Pathan, MBBS, MCEM
role: Principal Investigator
affiliation: Hamad Medical Corporation
last name: Prof. Peter A Cameron, MD,FACEM
role: Principal Investigator
affiliation: Hamad Medical Corporation
facility: 
country: Qatar
citation: Grissa MH, Claessens YE, Bouida W, Boubaker H, Boudhib L, Kerkeni W, Boukef R, Nouira S. Paracetamol vs piroxicam to relieve pain in renal colic. Results of a randomized controlled trial. Am J Emerg Med. 2011 Feb;29(2):203-6. doi: 10.1016/j.ajem.2009.09.019. Epub 2010 Oct 8.
PMID: 20934829
citation: Behzadnia MJ, Javadzadeh HR, Saboori F. Time of admission, gender and age: challenging factors in emergency renal colic - a preliminary study. Trauma Mon. 2012 Fall;17(3):329-32. doi: 10.5812/traumamon.6800. Epub 2012 Oct 10.
PMID: 24350118
citation: Shaden Salameh; Nurit Hiller; Meir Antopolsky; Fedaa Ghanem; Yigaal Abramovitz; Ruth Stalnikowics. Diclofenac versus Tramadol in the Treatment of Renal Colic: A Prospective, Randomized Trial. The Open Emergency Medicine Journal. 2011; 4: 9-13.
responsible party type: Principal Investigator
investigator affiliation: Hamad Medical Corporation
investigator full name: Dr. SAMEER PATHAN
investigator title: Research Fellow and Specialist
mesh term: Urinary Calculi
mesh term: Urolithiasis
mesh term: Colic
mesh term: Calculi
mesh term: Renal Colic
mesh term: Acetaminophen
mesh term: Diclofenac
mesh term: Morphine