<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/NCT03788889</url>
  </required_header>
  <id_info>
    <org_study_id>18-94</org_study_id>
    <nct_id>NCT03788889</nct_id>
  </id_info>
  <brief_title>Alcohol Withdrawal Syndrome Treated With Adjunctive Phenobarbital or Ketamine</brief_title>
  <acronym>PKAT</acronym>
  <official_title>A Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Phenobarbital and Ketamine Adjunctive Therapies in the Treatment of Alcohol Withdrawal Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Santa Barbara Cottage Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Santa Barbara Cottage Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this study will aim to determine if adding phenobarbital or ketamine to a&#xD;
      symptom-triggered benzodiazepine regimen decreases the rate of intensive care unit admissions&#xD;
      during the treatment of alcohol withdrawal syndrome when compared to symptom-triggered&#xD;
      benzodiazepine therapy alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to compare phenobarbital and ketamine adjunctive&#xD;
      therapies to lorazepam-based therapy in the treatment of acute alcohol withdrawal syndrome.&#xD;
&#xD;
      It is hypothesized that the use of an alternative agent, either phenobarbital or ketamine,&#xD;
      when used as an adjunct to symptom-triggered lorazepam therapy will significantly reduce the&#xD;
      rate of intensive care unit admissions and thereby reduce the total cost associated with&#xD;
      hospital admission for treatment of alcohol withdrawal syndrome.&#xD;
&#xD;
      Enrolled patients will be admitted to Santa Barbara Cottage Hospital where they will be&#xD;
      monitored with continuous pulse oximetry and cardiac telemetry. They will remain hospitalized&#xD;
      while undergoing study-guided therapy in addition to supportive care for acute alcohol&#xD;
      withdrawal syndrome. Patients will undergo standard of care therapy with lorazepam&#xD;
      symptom-triggered therapy regardless of study participation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    internal practice and policy limitations including time commitment / workflow issues&#xD;
  </why_stopped>
  <start_date type="Anticipated">April 12, 2019</start_date>
  <completion_date type="Actual">April 12, 2019</completion_date>
  <primary_completion_date type="Actual">April 12, 2019</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>
    <intervention_model_description>prospective, randomized control trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Each participant will be randomized according to a web-based randomization program employed by a research pharmacist once the Emergency Department provider deems the patient appropriate for inpatient treatment of alcohol withdrawal syndrome.&#xD;
Each medication will be packaged by Santa Barbara Cottage Hospital pharmacy. In order to blind both the clinicians and the participants, the pharmacy will provide medication bags that are identical. Therefore, Emergency Department nursing staff and physicians will be unaware of which study drug is being provided to the patient. Normal saline will be used as a placebo to mimic study drugs (phenobarbital and ketamine). Pharmacy will remain unblinded and maintain records of which treatment assignment is prepared for each patient.&#xD;
Treatment will be provided for the duration of the patient's hospitalization; therefore, treatment compliance will be documented in the electronic health record using the medication bag identifier.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Intensive Care Unit admission rate</measure>
    <time_frame>Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years</time_frame>
    <description>Number of admissions to the intensive care unit</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of withdrawal seizures</measure>
    <time_frame>Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years</time_frame>
    <description>Number of patients with documented seizures while treated for alcohol withdrawal syndrome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores</measure>
    <time_frame>Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years</time_frame>
    <description>CIWA-Ar scores (initial, maximum, discharge); Total score is cumulative of subscale measures: Minimum score is 0 (no evidence of alcohol withdrawal), Maximum score is 67 (severe alcohol withdrawal)&#xD;
Subscale measures:&#xD;
A) Nausea and vomiting (score 0-7); B) Tremor (score 0-7); C) Paroxysmal sweats (score 0-7); D) Anxiety (score 0-7); E) Tactile disturbances (score 0-7); F) Auditory disturbances (score 0-7); G) Visual disturbances (score 0-7); H) Headache, fullness in head (score 0-7); I) Agitation (score 0-7); J) Orientation and clouding of sensorium (score 0-4)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative dose of medication/s administered</measure>
    <time_frame>Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years</time_frame>
    <description>Cumulative dose of Lorazepam, Ketamine, and Phenobarbital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of refractory alcohol withdrawal requiring alternative sedation with dexmedetomidine, propofol or midazolam infusions</measure>
    <time_frame>Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years</time_frame>
    <description>Number of patients who require Dexmedetomidine, Propofol or Benzodiazepine continuous infusions and average dose while being treated for alcohol withdrawal syndrome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of mechanical ventilation</measure>
    <time_frame>Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years</time_frame>
    <description>Rate of intubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of alcohol withdrawal hallucinations</measure>
    <time_frame>Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years</time_frame>
    <description>Number of patients with documented auditory or visual hallucinations</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Alcohol Withdrawal Syndrome</condition>
  <arm_group>
    <arm_group_label>Lorazepam + Ketamine + Placebo A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ketamine - infusion (0.15 - 0.4 mg/kg/hr) and placebo injections titrated by increases of 0.075 mg/kg/hr every 30 minutes for Clinical Institute Withdrawal Assessment for Alcohol (revised version) (CIWA-Ar) greater than or equal to 10 in addition to lorazepam symptom-triggered therapy&#xD;
Ketamine dosing will be based on ideal body weight&#xD;
Ketamine infusion will be discontinued once CIWA-Ar less than 10 for 4 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lorazepam + Phenobarbital + Placebo B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Phenobarbital - IV push (260 mg loading followed by 130 mg q1 hour) with placebo infusion until CIWA-Ar less than 10 with a maximum daily dose of 10mg/kg in addition to lorazepam symptom-triggered dosing for recurrent symptoms (Gold 2007)&#xD;
Maximum daily dose will be used in order to prevent over sedation as well as provide adequate storage in pharmacy monitored refrigerators for study drugs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lorazepam + Placebo A + Placebo B</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Lorazepam will be administered every 30 minutes as indicated based on CIWA-Ar protocol for Cottage Health in addition to placebo injections and placebo infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>Ketamine infusion</description>
    <arm_group_label>Lorazepam + Ketamine + Placebo A</arm_group_label>
    <other_name>Ketalar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Phenobarbital</intervention_name>
    <description>Phenobarbital intravenous injection</description>
    <arm_group_label>Lorazepam + Phenobarbital + Placebo B</arm_group_label>
    <other_name>Solfoton, Luminal</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lorazepam</intervention_name>
    <description>Standard of Care</description>
    <arm_group_label>Lorazepam + Ketamine + Placebo A</arm_group_label>
    <arm_group_label>Lorazepam + Phenobarbital + Placebo B</arm_group_label>
    <arm_group_label>Lorazepam + Placebo A + Placebo B</arm_group_label>
    <other_name>Ativan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo A</intervention_name>
    <description>Placebo injection</description>
    <arm_group_label>Lorazepam + Ketamine + Placebo A</arm_group_label>
    <arm_group_label>Lorazepam + Placebo A + Placebo B</arm_group_label>
    <other_name>Normal saline</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo B</intervention_name>
    <description>Placebo infusion</description>
    <arm_group_label>Lorazepam + Phenobarbital + Placebo B</arm_group_label>
    <arm_group_label>Lorazepam + Placebo A + Placebo B</arm_group_label>
    <other_name>Normal saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primary admitting diagnosis of acute alcohol withdrawal syndrome based on&#xD;
             International Statistical Classification of Diseases and Related Health Problems 10th&#xD;
             Revision (ICD-10), code F10.3, F10.4.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant comorbid medical illness requiring Intensive Care Unit admission;&#xD;
&#xD;
          -  Pregnancy;&#xD;
&#xD;
          -  Inability to obtain intravenous access;&#xD;
&#xD;
          -  Child Pugh Class C; and&#xD;
&#xD;
          -  Allergy to study medications (phenobarbital, ketamine, lorazepam).&#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>Noah Stites-Hallet, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Santa Barbara Cottage Hospital</affiliation>
  </overall_official>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>December 22, 2018</study_first_submitted>
  <study_first_submitted_qc>December 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 2018</study_first_posted>
  <last_update_submitted>September 17, 2019</last_update_submitted>
  <last_update_submitted_qc>September 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lorazepam</keyword>
  <keyword>Ketamine</keyword>
  <keyword>Phenobarbital</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Substance Withdrawal Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
    <mesh_term>Lorazepam</mesh_term>
    <mesh_term>Phenobarbital</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/NCT03788889
org study id: 18-94
nct id: NCT03788889
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The goal of this study will aim to determine if adding phenobarbital or ketamine to a
      symptom-triggered benzodiazepine regimen decreases the rate of intensive care unit admissions
      during the treatment of alcohol withdrawal syndrome when compared to symptom-triggered
      benzodiazepine therapy alone.
The primary objective of this study is to compare phenobarbital and ketamine adjunctive
      therapies to lorazepam-based therapy in the treatment of acute alcohol withdrawal syndrome.

      It is hypothesized that the use of an alternative agent, either phenobarbital or ketamine,
      when used as an adjunct to symptom-triggered lorazepam therapy will significantly reduce the
      rate of intensive care unit admissions and thereby reduce the total cost associated with
      hospital admission for treatment of alcohol withdrawal syndrome.

      Enrolled patients will be admitted to Santa Barbara Cottage Hospital where they will be
      monitored with continuous pulse oximetry and cardiac telemetry. They will remain hospitalized
      while undergoing study-guided therapy in addition to supportive care for acute alcohol
      withdrawal syndrome. Patients will undergo standard of care therapy with lorazepam
      symptom-triggered therapy regardless of study participation.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: prospective, randomized control trial
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Each participant will be randomized according to a web-based randomization program employed by a research pharmacist once the Emergency Department provider deems the patient appropriate for inpatient treatment of alcohol withdrawal syndrome.
Each medication will be packaged by Santa Barbara Cottage Hospital pharmacy. In order to blind both the clinicians and the participants, the pharmacy will provide medication bags that are identical. Therefore, Emergency Department nursing staff and physicians will be unaware of which study drug is being provided to the patient. Normal saline will be used as a placebo to mimic study drugs (phenobarbital and ketamine). Pharmacy will remain unblinded and maintain records of which treatment assignment is prepared for each patient.
Treatment will be provided for the duration of the patient's hospitalization; therefore, treatment compliance will be documented in the electronic health record using the medication bag identifier.
measure: Intensive Care Unit admission rate
time frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years
description: Number of admissions to the intensive care unit
measure: Incidence of withdrawal seizures
time frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years
description: Number of patients with documented seizures while treated for alcohol withdrawal syndrome
measure: Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores
time frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years
description: CIWA-Ar scores (initial, maximum, discharge); Total score is cumulative of subscale measures: Minimum score is 0 (no evidence of alcohol withdrawal), Maximum score is 67 (severe alcohol withdrawal)
Subscale measures:
A) Nausea and vomiting (score 0-7); B) Tremor (score 0-7); C) Paroxysmal sweats (score 0-7); D) Anxiety (score 0-7); E) Tactile disturbances (score 0-7); F) Auditory disturbances (score 0-7); G) Visual disturbances (score 0-7); H) Headache, fullness in head (score 0-7); I) Agitation (score 0-7); J) Orientation and clouding of sensorium (score 0-4)
measure: Cumulative dose of medication/s administered
time frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years
description: Cumulative dose of Lorazepam, Ketamine, and Phenobarbital
measure: Incidence of refractory alcohol withdrawal requiring alternative sedation with dexmedetomidine, propofol or midazolam infusions
time frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years
description: Number of patients who require Dexmedetomidine, Propofol or Benzodiazepine continuous infusions and average dose while being treated for alcohol withdrawal syndrome
measure: Rate of mechanical ventilation
time frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years
description: Rate of intubation
measure: Incidence of alcohol withdrawal hallucinations
time frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years
description: Number of patients with documented auditory or visual hallucinations
arm group label: Lorazepam + Ketamine + Placebo A
arm group type: Active Comparator
description: Ketamine - infusion (0.15 - 0.4 mg/kg/hr) and placebo injections titrated by increases of 0.075 mg/kg/hr every 30 minutes for Clinical Institute Withdrawal Assessment for Alcohol (revised version) (CIWA-Ar) greater than or equal to 10 in addition to lorazepam symptom-triggered therapy
Ketamine dosing will be based on ideal body weight
Ketamine infusion will be discontinued once CIWA-Ar less than 10 for 4 hours
arm group label: Lorazepam + Phenobarbital + Placebo B
arm group type: Active Comparator
description: Phenobarbital - IV push (260 mg loading followed by 130 mg q1 hour) with placebo infusion until CIWA-Ar less than 10 with a maximum daily dose of 10mg/kg in addition to lorazepam symptom-triggered dosing for recurrent symptoms (Gold 2007)
Maximum daily dose will be used in order to prevent over sedation as well as provide adequate storage in pharmacy monitored refrigerators for study drugs
arm group label: Lorazepam + Placebo A + Placebo B
arm group type: Placebo Comparator
description: Lorazepam will be administered every 30 minutes as indicated based on CIWA-Ar protocol for Cottage Health in addition to placebo injections and placebo infusion
intervention type: Drug
intervention name: Ketamine
description: Ketamine infusion
arm group label: Lorazepam + Ketamine + Placebo A
other name: Ketalar
intervention type: Drug
intervention name: Phenobarbital
description: Phenobarbital intravenous injection
arm group label: Lorazepam + Phenobarbital + Placebo B
other name: Solfoton, Luminal
intervention type: Drug
intervention name: Lorazepam
description: Standard of Care
arm group label: Lorazepam + Ketamine + Placebo A
arm group label: Lorazepam + Phenobarbital + Placebo B
arm group label: Lorazepam + Placebo A + Placebo B
other name: Ativan
intervention type: Drug
intervention name: Placebo A
description: Placebo injection
arm group label: Lorazepam + Ketamine + Placebo A
arm group label: Lorazepam + Placebo A + Placebo B
other name: Normal saline
intervention type: Drug
intervention name: Placebo B
description: Placebo infusion
arm group label: Lorazepam + Phenobarbital + Placebo B
arm group label: Lorazepam + Placebo A + Placebo B
other name: Normal saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Noah Stites-Hallet, MD
role: Principal Investigator
affiliation: Santa Barbara Cottage Hospital
responsible party type: Sponsor
mesh term: Syndrome
mesh term: Substance Withdrawal Syndrome
mesh term: Ketamine
mesh term: Lorazepam
mesh term: Phenobarbital
sharing ipd: No