<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/NCT03770208</url>
  </required_header>
  <id_info>
    <org_study_id>PPIB0247S</org_study_id>
    <nct_id>NCT03770208</nct_id>
  </id_info>
  <brief_title>RIB PAIN (Rib Fractures Treated With Parental Analgesia With Infused LidocaiNe)</brief_title>
  <acronym>RIB PAIN</acronym>
  <official_title>A Randomized Control Trial of Intravenous Lidocaine for the Management of Traumatic Rib Fractures: a Single Trauma Centre Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Western University, Canada</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Western University, Canada</source>
  <oversight_info>
    <has_dmc>No</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>
      Traumatic rib fractures (RF) are a relatively common occurrence in patients of all ages, with&#xD;
      a 10% incidence in all trauma patients and are associated with significant morbidity and&#xD;
      mortality. Adequate analgesia is paramount for preventing pulmonary complications and can&#xD;
      reduce morbidity and mortality. There is longstanding evidence of lidocaine's effectiveness&#xD;
      and safety in the post-operative patient and the investigators hypothesize that this modality&#xD;
      may prove to be ideal in trauma patients with RF. Therefore, it is imperative that&#xD;
      intravenous lidocaine be investigated to ascertain if there is significant benefit for pain&#xD;
      reduction in patients who have sustained rib fractures.&#xD;
&#xD;
      A single-centre, double-blind, randomized control trial to evaluate the analgesic efficacy of&#xD;
      a 72-96 hour IV lidocaine infusion plus standard analgesics versus placebo infusion plus&#xD;
      standard analgesics will be performed on patients (age 18 or older) diagnosed with two or&#xD;
      more traumatic rib fractures ,from blunt thoracic trauma, requiring hospital admission at&#xD;
      Victoria Hospital.&#xD;
&#xD;
      The primary outcome is mean pain score, as measured on the Visual Analog Scale (VAS) when the&#xD;
      patient is at rest and with movement. Secondary outcomes are protocol adherence, patient&#xD;
      satisfaction as measured on the VAS, incidence of respiratory failure requiring mechanical&#xD;
      ventilation, hospital length of stay, ICU length of stay, mortality, incidence of lidocaine&#xD;
      toxicity, treatment regimens (use of additional non-opioid analgesics) and total morphine&#xD;
      equivalents used (including breakthrough doses).&#xD;
&#xD;
      This trial will serve to quantify the analgesic efficacy of intravenous lidocaine for&#xD;
      patients with traumatic rib fractures. Successful completion of a single centre trial will&#xD;
      inform the development of a multi-centre trial powered to demonstrate a reduction in&#xD;
      respiratory failure in the trauma population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This trial will use a randomized double blind design. All patients (age 18 or older)&#xD;
      diagnosed with two or more traumatic rib fractures requiring hospital admission at Victoria&#xD;
      Hospital will be identified at the time of admission by trauma team members and / or ICU&#xD;
      research assistants. Patients unable to understand or follow instructions in English or&#xD;
      French, and those unable to complete the Visual Analog Scale (VAS) for pain for any reason,&#xD;
      will be excluded.&#xD;
&#xD;
      Any physician member of the inpatient trauma service team, trauma nurse practitioner, or ICU&#xD;
      research assistants may approach patients and their families to discuss participation in the&#xD;
      trial. Research assistants will be responsible for providing the Letter of Information and&#xD;
      Consent Form to families, and storing them once complete. Consented patients will be&#xD;
      randomized at admission using the online randomization tool, like REDCAP, by pharmacy. Once&#xD;
      randomized, research assistants will contact pharmacy to order &quot;Study Drug&quot;, but will remain&#xD;
      blinded to study arm&#xD;
&#xD;
      Consented patients will receive either standard care (acetaminophen, NSAIDs, opioids) plus IV&#xD;
      placebo or standard care plus IV lidocaine using a fixed strategy with variable blocks and a&#xD;
      1:1 allocation ratio. The pharmacy will be the only party unblinded to randomization and will&#xD;
      distribute the &quot;Study Drug&quot; [either IV lidocaine or Lactated Ringer's (a clear colourless&#xD;
      solution that is indistinguishable from Lidocaine)] to study participants. All patients will&#xD;
      be followed throughout their hospital stay by our research assistants to assess pain and&#xD;
      secondary outcomes.&#xD;
&#xD;
      IV lidocaine will be administered as a bolus dose of 2 mg/kg (maximum dose 100 mg) followed&#xD;
      by a 2 mg/kg/hr infusion for 72-96 hrs. Lactated Ringer's will be administered at the same&#xD;
      overall rate to the control group. Patient pain scores will be accessed at the bedside using&#xD;
      the VAS at time 0hrs and every six hours for the duration of study drug infusion.&#xD;
&#xD;
      Daily monitoring of the patient will be performed by the trauma team and bedside nurses.&#xD;
      Clinical care will be conducted as usual with the exception of the provision of study drug,&#xD;
      the recording of pain Q6 hours, and the assessment of patient satisfaction at the end of the&#xD;
      72-96 hour infusion. All other patient data will be collected from the patient's EMR and&#xD;
      bedside chart. In accordance with LHSC hospital Lidocaine policy, all study patients will be&#xD;
      on telemetry to monitor for arrhythmias resulting from lidocaine toxicity. As the use of IV&#xD;
      lidocaine is already common in the LHSC patient population, all nursing staff are trained to&#xD;
      detect signs and symptoms of lidocaine toxicity, and will contact the treatment and research&#xD;
      teams if these develop. The study drug infusions will be stopped if any signs of toxicity are&#xD;
      seen. The treating team will be unblinded to randomization group in any cases of suspected&#xD;
      Lidocaine toxicity.&#xD;
&#xD;
      The primary outcome will be mean pain score calculated from the multiple VAS measures&#xD;
      performed during Lidocaine infusions when the patient is at rest and with movement. Secondary&#xD;
      outcomes are protocol adherence, patient satisfaction as measured on the VAS, incidence of&#xD;
      respiratory failure requiring mechanical ventilation, hospital length of stay, ICU length of&#xD;
      stay, mortality, incidence of lidocaine toxicity, treatment regimens (use of additional&#xD;
      non-opioid analgesics) and total morphine equivalents used (including breakthrough doses).&#xD;
      Secondary outcomes will be recorded by the ICU research assistants on a daily basis during&#xD;
      each patient's index stay. Research assistants will help administer the satisfaction survey&#xD;
      to patients as soon as possible following completion of the 72-96 hour Lidocaine infusion.&#xD;
      The methodology, pain and satisfaction reporting with VAS is very similar to the&#xD;
      investigator's previous work.&#xD;
&#xD;
      A sample size of 26 patients is required to find a difference between two independent group&#xD;
      means using the following parameters: (1) a 20% reduction in VAS score (20mm), (2) 90% power,&#xD;
      (3) probability of a Type I error = 5%, and s stand deviation of 15% (15mm).&#xD;
&#xD;
      An anticipated attrition rate of 20% will be used to ensure enough patients are included for&#xD;
      adequate power. Therefore a minimum of 32 patients will be enrolled in the study.&#xD;
&#xD;
      Continuous data will be reported as mean +/- standard deviation or median and interquartile&#xD;
      range, depending on the distribution of each data point. Categorical data will be reported as&#xD;
      percentages with corresponding 95% confidence intervals. The mean pain score will be compared&#xD;
      between treatment groups using Student's T-test. Findings with a Type I error rate &lt; 5% will&#xD;
      be considered statistically significant. Analyses of secondary outcomes will be primarily&#xD;
      descriptive. Any significance testing of these outcomes will be strictly&#xD;
      hypotheses-generating.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 6, 2019</start_date>
  <completion_date type="Anticipated">June 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2019</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>RCT, single site, double blinded</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>All parties involved until the end of trial. Pharmacy will be the only unblinded party as they need to prepare the study drugs.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Visual Analogue Scale (VAS) Score for Pain</measure>
    <time_frame>Pain score to be measured before treatment initiation and every 6 hours thereafter until 72-96 hours. Scores will be performed by bedside nursing.</time_frame>
    <description>The primary outcome will be mean pain score calculated from the multiple VAS measures performed during Lidocaine infusions when the patient is at rest and with movement. The VAS for pain is a continuous numerical scale, demonstrated by a horizontal or vertical line, 10 cm long, with verbal descriptors at each end demonstrating the extremes, +/- a central descriptor. It is a scale essentially from 1 to 10, with one being no pain and 10 being the worst pain possible. Subjects mark on the line their approximate pain score by drawing a transecting line. This will be measured with a ruler from the start point on the line and recorded as a data point.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Protocol Non-adherence</measure>
    <time_frame>Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.</time_frame>
    <description>Incidence of protocol violations with corresponding 95% confidence intervals. Descriptions of the deviations will be recorded. Types include, number of patients who received lidocaine that were not assigned to that group; number of patients who were assigned lidocaine and never received the study drug; non-weight based dosages of lidocaine; etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction as measured on the Visual Analogue Scale for Satisfaction</measure>
    <time_frame>Research assistants will help administer the satisfaction survey to patients as soon as possible following completion of the 72-96 hour Lidocaine infusion.</time_frame>
    <description>The VAS for pain is a continuous numerical scale, demonstrated by a horizontal or vertical line, 10 cm long, with verbal descriptors at each end demonstrating the extremes, +/- a central descriptor. It is measured from one, representing not satisfied at all to ten, representing completely satisfied. Subjects mark on the line their approximate pain score by drawing a transecting line. This will be measured with a ruler from the start point on the line and recorded as a data point. Score will be performed on a VAS at the end of the treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of respiratory failure requiring mechanical ventilation</measure>
    <time_frame>Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.</time_frame>
    <description>Categorical data will be reported as percentages with corresponding 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.</time_frame>
    <description>Continuous data will be reported as mean +/- standard deviation or median and interquartile range, depending on the distribution of each data point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.</time_frame>
    <description>Continuous data will be reported as mean +/- standard deviation or median and interquartile range, depending on the distribution of each data point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Mortality</measure>
    <time_frame>Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period or when the mortality occurs.</time_frame>
    <description>Categorical data will be reported as percentages with corresponding 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of lidocaine toxicity/adverse events</measure>
    <time_frame>Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.</time_frame>
    <description>Categorical data will be reported as percentages with corresponding 95% confidence intervals. Toxic symptoms will also be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment regimens (use of additional non-opioid analgesics): Medication type</measure>
    <time_frame>Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.</time_frame>
    <description>Any non-opioid analgesic medications used will be recorded. Incidence of each medications' use will be reported as percentages with corresponding 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment regimens (use of additional non-opioid analgesics): Dosages</measure>
    <time_frame>Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.</time_frame>
    <description>Dosages of any non-opioid analgesic medications used will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment regimens (use of additional non-opioid analgesics): Frequency</measure>
    <time_frame>Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.</time_frame>
    <description>Dosing frequency of any non-opioid analgesic medications used will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment regimens (use of additional non-opioid analgesics): Delivery Route</measure>
    <time_frame>Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.</time_frame>
    <description>Route of delivery of any non-opioid analgesic medications used will be recorded. Categories include by mouth (PO); subcutaneously (SubQ); Intravenously (IV); and other.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total morphine equivalents used (including breakthrough doses)</measure>
    <time_frame>Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.</time_frame>
    <description>Dose will be the cumulative opioid dose over the 72-96 hour period. Conversion to Morphine Equivalents will be calculated. Continuous data will be reported as mean +/- standard deviation or median and interquartile range, depending on the distribution of each data point.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">26</enrollment>
  <condition>Rib Fracture Multiple</condition>
  <condition>Pain, Chest</condition>
  <condition>Pain, Acute</condition>
  <condition>Respiratory Failure</condition>
  <condition>Thoracic Injuries</condition>
  <condition>Trauma Chest</condition>
  <arm_group>
    <arm_group_label>Control: Standard Care + Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Standard care (acetaminophen, NSAIDs, opioids, gabapentin) as directed by MRP care team plus IV placebo (Lactated Ringers). Lactated Ringers will be delivered as a &quot;initial bolus&quot; and then run as a continuous infusion to mimic the volume (as per Kg) of study drug for 72-96 hours. Standard care will be determined by the care team with no limitations introduced by the research team. Medications utilized and dosing regimes will be recorded after the intervention.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention: Lidocaine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Standard care (acetaminophen, NSAIDs, opioids, gabapentin) as directed by MRP care team plus IV lidocaine. IV lidocaine will be administered as a bolus dose of 2 mg/kg (maximum dose 100 mg) followed by a 2 mg/kg/hr infusion for 72-96 hrs.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intervention: Lidocaine</intervention_name>
    <description>IV Lidocaine bolus plus infusion. Weight based.</description>
    <arm_group_label>Intervention: Lidocaine</arm_group_label>
    <other_name>Lidocaine Hydrochloride</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Control: Standard Care + Placebo</intervention_name>
    <description>Placebo IV bolus and infusion. Weight based to mimic lidocaine volume.</description>
    <arm_group_label>Control: Standard Care + Placebo</arm_group_label>
    <other_name>Lactated Ringers</other_name>
    <other_name>Ringer's Lactate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All adult patients, 18 years or older, admitted to Victoria Hospital's Trauma Service&#xD;
             with two or more traumatic rib fractures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients under 18 years old&#xD;
&#xD;
          -  Patients who sustained complex trauma with multiple other injuries or have decreased&#xD;
             LOC or required intubation at admission&#xD;
&#xD;
          -  Patients with a known allergy/sensitivity to Lidocaine or other local anesthetic,&#xD;
             amide anesthetics or components of the solution&#xD;
&#xD;
          -  Patients with a known history of hypersensitivity to methylparaben and/or&#xD;
             propylparaben (preservatives used in multidose solutions), or to their metabolite para&#xD;
             amino benzoic acid&#xD;
&#xD;
          -  Patients who do not speak English with adequate fluency to consent or participate in&#xD;
             the VAS survey&#xD;
&#xD;
          -  Patients receiving epidural analgesia for another reason&#xD;
&#xD;
          -  Patients with pre-existing cardiac arrhythmias including Adam-Stokes syndrome; Wolff-&#xD;
             Parkinson-White syndrome; and severe degrees of sinoatrial, atrioventricular, or&#xD;
             intraventricular heart block (except in patients with a functioning artificial&#xD;
             pacemaker)&#xD;
&#xD;
          -  Patients who are known to be pregnant or breast feeding, as identified on Past Medical&#xD;
             History, or by initial laboratory investigations performed as a part of standard&#xD;
             trauma team assessment&#xD;
&#xD;
          -  Patients with known hepatic/renal disease, as identified on Past Medical History, or&#xD;
             by initial laboratory investigations performed as a part of standard trauma team&#xD;
             assessment&#xD;
&#xD;
          -  Patients who refuse inclusion&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ian Ball, MD, MSc (Epi), FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>London Health Sciences Centre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ian Ball, MD, MSc (Epi), FRCPC</last_name>
    <phone>519.685.8500</phone>
    <phone_ext>71513</phone_ext>
    <email>Ian.Ball@lhsc.on.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>London Health Sciences Centre - Victoria Hospital</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5W9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ian Ball, MD</last_name>
      <phone>519.685.8500</phone>
      <phone_ext>71513</phone_ext>
      <email>Ian.Ball@lhsc.on.ca</email>
    </contact>
    <investigator>
      <last_name>Petrease H Patton, MD, MSc, HBSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ian Ball, MD, MSc, FRCPC</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kelly Vogt, MD, MSc, FRCSC</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Neil Parry, MD, FRCSC, BSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Arjun Kundra, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lauren Lauren Zarnett, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Fran Priestap, MSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lynn Kelly, BPharm</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
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  </reference>
  <reference>
    <citation>Cherny N, Ripamonti C, Pereira J, Davis C, Fallon M, McQuay H, Mercadante S, Pasternak G, Ventafridda V; Expert Working Group of the European Association of Palliative Care Network. Strategies to manage the adverse effects of oral morphine: an evidence-based report. J Clin Oncol. 2001 May 1;19(9):2542-54. doi: 10.1200/JCO.2001.19.9.2542.</citation>
    <PMID>11331334</PMID>
  </reference>
  <reference>
    <citation>Ball IM, Seabrook J, Desai N, Allen L, Anderson S. Dilute proparacaine for the management of acute corneal injuries in the emergency department. CJEM. 2010 Sep;12(5):389-96. doi: 10.1017/s1481803500012537.</citation>
    <PMID>20880433</PMID>
  </reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <last_update_submitted>October 3, 2019</last_update_submitted>
  <last_update_submitted_qc>October 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Western University, Canada</investigator_affiliation>
    <investigator_full_name>Ian Ball</investigator_full_name>
    <investigator_title>Chair, Critical Care Western Research and Scholar Program Director; Consultant, Critical Care Medicine; Assistant Professor, Department of Medicine and Department of Epidemiology &amp; Biostatistics</investigator_title>
  </responsible_party>
  <keyword>Lidocaine Infusions</keyword>
  <keyword>Thoracic trauma</keyword>
  <keyword>Analgesic Management</keyword>
  <keyword>Rib Fractures</keyword>
  <keyword>Pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Acute Pain</mesh_term>
    <mesh_term>Chest Pain</mesh_term>
    <mesh_term>Fractures, Bone</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
    <mesh_term>Rib Fractures</mesh_term>
    <mesh_term>Thoracic Injuries</mesh_term>
    <mesh_term>Fractures, Multiple</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lidocaine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03770208
org study id: PPIB0247S
nct id: NCT03770208
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Traumatic rib fractures (RF) are a relatively common occurrence in patients of all ages, with
      a 10% incidence in all trauma patients and are associated with significant morbidity and
      mortality. Adequate analgesia is paramount for preventing pulmonary complications and can
      reduce morbidity and mortality. There is longstanding evidence of lidocaine's effectiveness
      and safety in the post-operative patient and the investigators hypothesize that this modality
      may prove to be ideal in trauma patients with RF. Therefore, it is imperative that
      intravenous lidocaine be investigated to ascertain if there is significant benefit for pain
      reduction in patients who have sustained rib fractures.

      A single-centre, double-blind, randomized control trial to evaluate the analgesic efficacy of
      a 72-96 hour IV lidocaine infusion plus standard analgesics versus placebo infusion plus
      standard analgesics will be performed on patients (age 18 or older) diagnosed with two or
      more traumatic rib fractures ,from blunt thoracic trauma, requiring hospital admission at
      Victoria Hospital.

      The primary outcome is mean pain score, as measured on the Visual Analog Scale (VAS) when the
      patient is at rest and with movement. Secondary outcomes are protocol adherence, patient
      satisfaction as measured on the VAS, incidence of respiratory failure requiring mechanical
      ventilation, hospital length of stay, ICU length of stay, mortality, incidence of lidocaine
      toxicity, treatment regimens (use of additional non-opioid analgesics) and total morphine
      equivalents used (including breakthrough doses).

      This trial will serve to quantify the analgesic efficacy of intravenous lidocaine for
      patients with traumatic rib fractures. Successful completion of a single centre trial will
      inform the development of a multi-centre trial powered to demonstrate a reduction in
      respiratory failure in the trauma population.
This trial will use a randomized double blind design. All patients (age 18 or older)
      diagnosed with two or more traumatic rib fractures requiring hospital admission at Victoria
      Hospital will be identified at the time of admission by trauma team members and / or ICU
      research assistants. Patients unable to understand or follow instructions in English or
      French, and those unable to complete the Visual Analog Scale (VAS) for pain for any reason,
      will be excluded.

      Any physician member of the inpatient trauma service team, trauma nurse practitioner, or ICU
      research assistants may approach patients and their families to discuss participation in the
      trial. Research assistants will be responsible for providing the Letter of Information and
      Consent Form to families, and storing them once complete. Consented patients will be
      randomized at admission using the online randomization tool, like REDCAP, by pharmacy. Once
      randomized, research assistants will contact pharmacy to order "Study Drug", but will remain
      blinded to study arm

      Consented patients will receive either standard care (acetaminophen, NSAIDs, opioids) plus IV
      placebo or standard care plus IV lidocaine using a fixed strategy with variable blocks and a
      1:1 allocation ratio. The pharmacy will be the only party unblinded to randomization and will
      distribute the "Study Drug" [either IV lidocaine or Lactated Ringer's (a clear colourless
      solution that is indistinguishable from Lidocaine)] to study participants. All patients will
      be followed throughout their hospital stay by our research assistants to assess pain and
      secondary outcomes.

      IV lidocaine will be administered as a bolus dose of 2 mg/kg (maximum dose 100 mg) followed
      by a 2 mg/kg/hr infusion for 72-96 hrs. Lactated Ringer's will be administered at the same
      overall rate to the control group. Patient pain scores will be accessed at the bedside using
      the VAS at time 0hrs and every six hours for the duration of study drug infusion.

      Daily monitoring of the patient will be performed by the trauma team and bedside nurses.
      Clinical care will be conducted as usual with the exception of the provision of study drug,
      the recording of pain Q6 hours, and the assessment of patient satisfaction at the end of the
      72-96 hour infusion. All other patient data will be collected from the patient's EMR and
      bedside chart. In accordance with LHSC hospital Lidocaine policy, all study patients will be
      on telemetry to monitor for arrhythmias resulting from lidocaine toxicity. As the use of IV
      lidocaine is already common in the LHSC patient population, all nursing staff are trained to
      detect signs and symptoms of lidocaine toxicity, and will contact the treatment and research
      teams if these develop. The study drug infusions will be stopped if any signs of toxicity are
      seen. The treating team will be unblinded to randomization group in any cases of suspected
      Lidocaine toxicity.

      The primary outcome will be mean pain score calculated from the multiple VAS measures
      performed during Lidocaine infusions when the patient is at rest and with movement. Secondary
      outcomes are protocol adherence, patient satisfaction as measured on the VAS, incidence of
      respiratory failure requiring mechanical ventilation, hospital length of stay, ICU length of
      stay, mortality, incidence of lidocaine toxicity, treatment regimens (use of additional
      non-opioid analgesics) and total morphine equivalents used (including breakthrough doses).
      Secondary outcomes will be recorded by the ICU research assistants on a daily basis during
      each patient's index stay. Research assistants will help administer the satisfaction survey
      to patients as soon as possible following completion of the 72-96 hour Lidocaine infusion.
      The methodology, pain and satisfaction reporting with VAS is very similar to the
      investigator's previous work.

      A sample size of 26 patients is required to find a difference between two independent group
      means using the following parameters: (1) a 20% reduction in VAS score (20mm), (2) 90% power,
      (3) probability of a Type I error = 5%, and s stand deviation of 15% (15mm).

      An anticipated attrition rate of 20% will be used to ensure enough patients are included for
      adequate power. Therefore a minimum of 32 patients will be enrolled in the study.

      Continuous data will be reported as mean +/- standard deviation or median and interquartile
      range, depending on the distribution of each data point. Categorical data will be reported as
      percentages with corresponding 95% confidence intervals. The mean pain score will be compared
      between treatment groups using Student's T-test. Findings with a Type I error rate < 5% will
      be considered statistically significant. Analyses of secondary outcomes will be primarily
      descriptive. Any significance testing of these outcomes will be strictly
      hypotheses-generating.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: RCT, single site, double blinded
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: All parties involved until the end of trial. Pharmacy will be the only unblinded party as they need to prepare the study drugs.
measure: Mean Visual Analogue Scale (VAS) Score for Pain
time frame: Pain score to be measured before treatment initiation and every 6 hours thereafter until 72-96 hours. Scores will be performed by bedside nursing.
description: The primary outcome will be mean pain score calculated from the multiple VAS measures performed during Lidocaine infusions when the patient is at rest and with movement. The VAS for pain is a continuous numerical scale, demonstrated by a horizontal or vertical line, 10 cm long, with verbal descriptors at each end demonstrating the extremes, +/- a central descriptor. It is a scale essentially from 1 to 10, with one being no pain and 10 being the worst pain possible. Subjects mark on the line their approximate pain score by drawing a transecting line. This will be measured with a ruler from the start point on the line and recorded as a data point.
measure: Incidence of Protocol Non-adherence
time frame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
description: Incidence of protocol violations with corresponding 95% confidence intervals. Descriptions of the deviations will be recorded. Types include, number of patients who received lidocaine that were not assigned to that group; number of patients who were assigned lidocaine and never received the study drug; non-weight based dosages of lidocaine; etc.
measure: Patient satisfaction as measured on the Visual Analogue Scale for Satisfaction
time frame: Research assistants will help administer the satisfaction survey to patients as soon as possible following completion of the 72-96 hour Lidocaine infusion.
description: The VAS for pain is a continuous numerical scale, demonstrated by a horizontal or vertical line, 10 cm long, with verbal descriptors at each end demonstrating the extremes, +/- a central descriptor. It is measured from one, representing not satisfied at all to ten, representing completely satisfied. Subjects mark on the line their approximate pain score by drawing a transecting line. This will be measured with a ruler from the start point on the line and recorded as a data point. Score will be performed on a VAS at the end of the treatment period.
measure: Incidence of respiratory failure requiring mechanical ventilation
time frame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
description: Categorical data will be reported as percentages with corresponding 95% confidence intervals.
measure: Hospital length of stay
time frame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
description: Continuous data will be reported as mean +/- standard deviation or median and interquartile range, depending on the distribution of each data point.
measure: ICU length of stay
time frame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
description: Continuous data will be reported as mean +/- standard deviation or median and interquartile range, depending on the distribution of each data point.
measure: Incidence of Mortality
time frame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period or when the mortality occurs.
description: Categorical data will be reported as percentages with corresponding 95% confidence intervals.
measure: Incidence of lidocaine toxicity/adverse events
time frame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
description: Categorical data will be reported as percentages with corresponding 95% confidence intervals. Toxic symptoms will also be recorded.
measure: Treatment regimens (use of additional non-opioid analgesics): Medication type
time frame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
description: Any non-opioid analgesic medications used will be recorded. Incidence of each medications' use will be reported as percentages with corresponding 95% confidence intervals.
measure: Treatment regimens (use of additional non-opioid analgesics): Dosages
time frame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
description: Dosages of any non-opioid analgesic medications used will be recorded.
measure: Treatment regimens (use of additional non-opioid analgesics): Frequency
time frame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
description: Dosing frequency of any non-opioid analgesic medications used will be recorded.
measure: Treatment regimens (use of additional non-opioid analgesics): Delivery Route
time frame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
description: Route of delivery of any non-opioid analgesic medications used will be recorded. Categories include by mouth (PO); subcutaneously (SubQ); Intravenously (IV); and other.
measure: Total morphine equivalents used (including breakthrough doses)
time frame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
description: Dose will be the cumulative opioid dose over the 72-96 hour period. Conversion to Morphine Equivalents will be calculated. Continuous data will be reported as mean +/- standard deviation or median and interquartile range, depending on the distribution of each data point.
arm group label: Control: Standard Care + Placebo
arm group type: Placebo Comparator
description: Standard care (acetaminophen, NSAIDs, opioids, gabapentin) as directed by MRP care team plus IV placebo (Lactated Ringers). Lactated Ringers will be delivered as a "initial bolus" and then run as a continuous infusion to mimic the volume (as per Kg) of study drug for 72-96 hours. Standard care will be determined by the care team with no limitations introduced by the research team. Medications utilized and dosing regimes will be recorded after the intervention.
arm group label: Intervention: Lidocaine
arm group type: Experimental
description: Standard care (acetaminophen, NSAIDs, opioids, gabapentin) as directed by MRP care team plus IV lidocaine. IV lidocaine will be administered as a bolus dose of 2 mg/kg (maximum dose 100 mg) followed by a 2 mg/kg/hr infusion for 72-96 hrs.
intervention type: Drug
intervention name: Intervention: Lidocaine
description: IV Lidocaine bolus plus infusion. Weight based.
arm group label: Intervention: Lidocaine
other name: Lidocaine Hydrochloride
intervention type: Drug
intervention name: Control: Standard Care + Placebo
description: Placebo IV bolus and infusion. Weight based to mimic lidocaine volume.
arm group label: Control: Standard Care + Placebo
other name: Lactated Ringers
other name: Ringer's Lactate
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ian Ball, MD, MSc (Epi), FRCPC
role: Principal Investigator
affiliation: London Health Sciences Centre
last name: Ian Ball, MD, MSc (Epi), FRCPC
phone: 519.685.8500
phone ext: 71513
email: Ian.Ball@lhsc.on.ca
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Canada
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PMID: 12634549
citation: Bulger EM, Edwards T, Klotz P, Jurkovich GJ. Epidural analgesia improves outcome after multiple rib fractures. Surgery. 2004 Aug;136(2):426-30. doi: 10.1016/j.surg.2004.05.019.
PMID: 15300210
citation: Arendt K, Segal S. Why epidurals do not always work. Rev Obstet Gynecol. 2008 Spring;1(2):49-55.
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citation: McCarthy GC, Megalla SA, Habib AS. Impact of intravenous lidocaine infusion on postoperative analgesia and recovery from surgery: a systematic review of randomized controlled trials. Drugs. 2010 Jun 18;70(9):1149-63. doi: 10.2165/10898560-000000000-00000.
PMID: 20518581
citation: Vigneault L, Turgeon AF, Cote D, Lauzier F, Zarychanski R, Moore L, McIntyre LA, Nicole PC, Fergusson DA. Perioperative intravenous lidocaine infusion for postoperative pain control: a meta-analysis of randomized controlled trials. Can J Anaesth. 2011 Jan;58(1):22-37. doi: 10.1007/s12630-010-9407-0.
PMID: 21061107
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PMID: 28386401
citation: Nguyen M, Vandenbroucke F, Roy JD, Beaulieu D, Seal RF, Lapointe R, Dagenais M, Roy A, Massicotte L. Evaluation of the addition of bupivacaine to intrathecal morphine and fentanyl for postoperative pain management in laparascopic liver resection. Reg Anesth Pain Med. 2010 May-Jun;35(3):261-6. doi: 10.1097/AAP.0b013e3181de12e4.
PMID: 20921837
citation: Cherny N, Ripamonti C, Pereira J, Davis C, Fallon M, McQuay H, Mercadante S, Pasternak G, Ventafridda V; Expert Working Group of the European Association of Palliative Care Network. Strategies to manage the adverse effects of oral morphine: an evidence-based report. J Clin Oncol. 2001 May 1;19(9):2542-54. doi: 10.1200/JCO.2001.19.9.2542.
PMID: 11331334
citation: Ball IM, Seabrook J, Desai N, Allen L, Anderson S. Dilute proparacaine for the management of acute corneal injuries in the emergency department. CJEM. 2010 Sep;12(5):389-96. doi: 10.1017/s1481803500012537.
PMID: 20880433
responsible party type: Principal Investigator
investigator affiliation: Western University, Canada
investigator full name: Ian Ball
investigator title: Chair, Critical Care Western Research and Scholar Program Director; Consultant, Critical Care Medicine; Assistant Professor, Department of Medicine and Department of Epidemiology & Biostatistics
mesh term: Respiratory Insufficiency
mesh term: Acute Pain
mesh term: Chest Pain
mesh term: Fractures, Bone
mesh term: Wounds and Injuries
mesh term: Rib Fractures
mesh term: Thoracic Injuries
mesh term: Fractures, Multiple
mesh term: Lidocaine
sharing ipd: No