xml: <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/NCT06013345</url>
    </required_header>
    <id_info>
      <org_study_id>Coopertaive-PFA</org_study_id>
      <nct_id>NCT06013345</nct_id>
    </id_info>
    <brief_title>COnventional vs. Optimised PERiprocedural Analgosedation vs. Total IntraVEnous Anaesthesia for Pulsed-Field Ablation (COOPERATIVE-PFA)</brief_title>
    <official_title>Conventional vs. Optimised Periprocedural Analgosedation vs. Total Intravenous Anaesthesia for Pulsed-field Ablation: a Randomised Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Charles University, Czech Republic</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Charles University, Czech Republic</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        A prospective single blinded (subject blinded) 1:1:1 randomised control trial with three&#xD;
        parallel arms testing superiority of analgosedation regimen based on remimazolam and total&#xD;
        intravenous anesthesia over propofol based analgosedation. The primary composite endpoint&#xD;
        consists of hypoxaemia, hypotension, or hypertension requiring intervention.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">January 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2024</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Study arms, analgosedation and TIVA protocols:&#xD;
  Conventional propofol analgosedation (arm P): current standard practice in most centres, a combination of short-acting benzodiazepine (midazolam) at the beginning, short-acting opioid (sufentanil in this study) and propofol boluses before and during the application of ablation pulses with unsecured airway&#xD;
  Optimised continuous intravenous analgosedation (arm R): ultrashort-acting benzodiazepine (remimazolam) and ketamine with unsecured airway&#xD;
  Total intravenous anaesthesia with secured airway (arm TIVA): continuous propofol infusion using target controlled infusion (TCI) and short acting opioid boluses - sufentanil</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Participant)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Primary composite endpoint (rate of hypoxaemia, hypotension, or hypertension events)</measure>
      <time_frame>Procedure duration</time_frame>
      <description>Composite endpoint consisting of the rate of (1) hypoxaemia events requiring intervention, (2) hypotension events requiring intervention or leading to the procedure interruption, or (3) hypertension events requiring intervention</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Total number of haemodynamic instability events (hypoxemia, hypotension, hypertension; defined above), each five minutes of a continuous instability counts as a new event, as well as an instability persisting despite an intervention</measure>
      <time_frame>Procedure duration</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total number of: a) hypoxemia events hypoxaemia &lt;85% (more than 30s) b) hypotension events = systolic blood pressure (SBP) &lt; 85 mmHg (more than 30s) c) hypertension event = SBP &gt; 200 mmHg (more than 30s)</measure>
      <time_frame>Procedure duration</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total number of interventions a) jaw thrust b) nasopharyngeal airway administration c) LMA / orotracheal intubation d) increasing FiO2 (oxygen flow) e) hypotensive drugs administration f) vasoactive drugs administration (ephedrine, noradrenaline)</measure>
      <time_frame>Procedure duration</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total procedural time</measure>
      <time_frame>Procedure duration</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Analgosedation depth by bispectral (BIS) monitoring: area under the curve of BIS index (measured every 3 minutes during the procedure)</measure>
      <time_frame>Procedure duration</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Procedural sedation quality</measure>
      <time_frame>12-24 hours after the procedure</time_frame>
      <description>PROcedural Sedation Assessment Survey - a previously validated form</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Difficult sedation score</measure>
      <time_frame>Procedure duration</time_frame>
      <description>1-10 scale (10 = the worst), reported by an anaesthesiologist</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Operator's satisfaction score</measure>
      <time_frame>Procedure duration</time_frame>
      <description>1-10 scale (10 = the worst), reported by the operating physician</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total number of serious adverse events</measure>
      <time_frame>From randomization until discharge</time_frame>
      <description>death, cardiopulmonary resuscitation (chest compression or adrenaline administration), an emergency intubation or prolonged stay in intensive care unit</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>carbon dioxide partial pressure after the procedure</measure>
      <time_frame>blood sample taken after the procedure (up to 10 minutes)</time_frame>
      <description>partial pressure (kPa) of CO2 measured in an arterial blood sample</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">126</enrollment>
    <condition>Atrial Fibrillation</condition>
    <arm_group>
      <arm_group_label>Arm P</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients in arm P will be administered 2-3 mg midazolam i.v. before the beginning of the procedure, 5-10 mcg sufentanil i.v. and a loading dose of propofol 0,8-1,0 mg/kg in 2-5 minutes before the start of the ablation phase. During the procedure, boluses of 0,5 mg/kg propofol will be repeated as needed, in case of inappropriate analgosedation, boluses of midazolam and/or sufentanil can be repeated.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm R</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients in arm R will be administered 2,5 mg loading dose of remimazolam followed by continuous infusion at 0,5 mg/h/kg of ideal body weight (IBW, calculated using the Miller formula) and a dose of ketamine 1 mg/kg (ideal body weight) 2-5 minutes before the beginning of the ablation phase. In case of inadequate sedation depth, a bolus of 2,5 mg remimazolam can be repeated as needed. In case the patient shows signs of pain or discomfort, a single dose of ketamine - 0,5 mg/kg IBW - will be administered, followed by a bolus of 5-10 mcg sufentanil if needed. The infusion will be stopped as the last ablation pulses are delivered</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm TIVA (Total Intravenous Anesthesia)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>General anaesthesia in patients randomised in arm TIVA will be induced and maintained with a bolus of 10 mcg sufentanil and propofol dosed by TCI system, model Schneider (plasma effect setting). The target plasma concentration for propofol will be set at 5-8 mcg/ml at induction and 4-6 mcg/ml for the rest of the procedure. After the induction, a laryngeal mask (LMA) will be inserted, the patient will be ventilated with 0,3 - 0,4 fraction of inspired oxygen (FiO2), minute ventilation set to achieve end tidal CO2 30 - 40 mmHg. At the beginning of the ablation phase, one bolus of 5-10 mcg sufentanil can be repeated. The dosage of TIVA can be changed so that no sign of discomfort is observed in the patient during ablation pulses. After the last ablation pulse is delivered, infusion of propofol will be ceased and LMA extracted at the return of consciousness.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Remimazolam</intervention_name>
      <description>analgosedation without secured airway</description>
      <arm_group_label>Arm R</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Propofol</intervention_name>
      <description>analgosedation with secured airway</description>
      <arm_group_label>Arm P</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Propofol</intervention_name>
      <description>TIVA with secured airway</description>
      <arm_group_label>Arm TIVA (Total Intravenous Anesthesia)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Atrial fibrillation (AF) (paroxysmal, persistent or long standing persistent) with&#xD;
               indication for catheter ablation&#xD;
  &#xD;
            -  Age above 18 years&#xD;
  &#xD;
            -  Capacity to give informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Heart failure (NYHA III-IV), irrespective of left ventricular ejection fraction&#xD;
  &#xD;
            -  Left ventricular ejection fraction &lt; 40%&#xD;
  &#xD;
            -  Significant valvulopathy (moderate or severe aortic stenosis, severe mitral&#xD;
               regurgitation, severe aortic regurgitation, moderate and severe mitral stenosis)&#xD;
  &#xD;
            -  Tricuspid regurgitation velocity above 2.8m/s&#xD;
  &#xD;
            -  Obstructive sleep apnoea syndrome&#xD;
  &#xD;
            -  Low oxygen saturation (&lt;93%) at baseline&#xD;
  &#xD;
            -  High aspiration risk (hiatal hernia, gastroesophageal reflux disease on chronic&#xD;
               pharmacotherapy)&#xD;
  &#xD;
            -  Hypersensitivity to the study drugs&#xD;
  &#xD;
            -  Chronic kidney disease (stage 4 and 5 of CKD), liver cirrhosis&#xD;
  &#xD;
            -  Anticipated difficult airways&#xD;
  &#xD;
            -  ASA (American Society of Anaesthesiologists) score &gt; 4&#xD;
  &#xD;
            -  Schizophrenia&#xD;
  &#xD;
            -  Epilepsy&#xD;
  &#xD;
            -  Other individual contraindications (will be reported in detail)&#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_contact>
      <last_name>Marek Hozman, MD</last_name>
      <phone>+420 267 161 111</phone>
      <email>marek.hozman@fnkv.cz</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Charles University, Czech Republic</investigator_affiliation>
      <investigator_full_name>Marek Hozman</investigator_full_name>
      <investigator_title>Principal investigator</investigator_title>
    </responsible_party>
    <keyword>Analgosedation</keyword>
    <keyword>Remimazolam</keyword>
    <keyword>Atrial Fibrillation</keyword>
    <keyword>Pulsed field ablation</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Atrial Fibrillation</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Propofol</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06013345
  org study id: Coopertaive-PFA
  nct id: NCT06013345
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  A prospective single blinded (subject blinded) 1:1:1 randomised control trial with three
        parallel arms testing superiority of analgosedation regimen based on remimazolam and total
        intravenous anesthesia over propofol based analgosedation. The primary composite endpoint
        consists of hypoxaemia, hypotension, or hypertension requiring intervention.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Study arms, analgosedation and TIVA protocols:
  Conventional propofol analgosedation (arm P): current standard practice in most centres, a combination of short-acting benzodiazepine (midazolam) at the beginning, short-acting opioid (sufentanil in this study) and propofol boluses before and during the application of ablation pulses with unsecured airway
  Optimised continuous intravenous analgosedation (arm R): ultrashort-acting benzodiazepine (remimazolam) and ketamine with unsecured airway
  Total intravenous anaesthesia with secured airway (arm TIVA): continuous propofol infusion using target controlled infusion (TCI) and short acting opioid boluses - sufentanil
  primary purpose: Treatment
  masking: Single (Participant)
  measure: Primary composite endpoint (rate of hypoxaemia, hypotension, or hypertension events)
  time frame: Procedure duration
  description: Composite endpoint consisting of the rate of (1) hypoxaemia events requiring intervention, (2) hypotension events requiring intervention or leading to the procedure interruption, or (3) hypertension events requiring intervention
  measure: Total number of haemodynamic instability events (hypoxemia, hypotension, hypertension; defined above), each five minutes of a continuous instability counts as a new event, as well as an instability persisting despite an intervention
  time frame: Procedure duration
  measure: Total number of: a) hypoxemia events hypoxaemia <85% (more than 30s) b) hypotension events = systolic blood pressure (SBP) < 85 mmHg (more than 30s) c) hypertension event = SBP > 200 mmHg (more than 30s)
  time frame: Procedure duration
  measure: Total number of interventions a) jaw thrust b) nasopharyngeal airway administration c) LMA / orotracheal intubation d) increasing FiO2 (oxygen flow) e) hypotensive drugs administration f) vasoactive drugs administration (ephedrine, noradrenaline)
  time frame: Procedure duration
  measure: Total procedural time
  time frame: Procedure duration
  measure: Analgosedation depth by bispectral (BIS) monitoring: area under the curve of BIS index (measured every 3 minutes during the procedure)
  time frame: Procedure duration
  measure: Procedural sedation quality
  time frame: 12-24 hours after the procedure
  description: PROcedural Sedation Assessment Survey - a previously validated form
  measure: Difficult sedation score
  time frame: Procedure duration
  description: 1-10 scale (10 = the worst), reported by an anaesthesiologist
  measure: Operator's satisfaction score
  time frame: Procedure duration
  description: 1-10 scale (10 = the worst), reported by the operating physician
  measure: Total number of serious adverse events
  time frame: From randomization until discharge
  description: death, cardiopulmonary resuscitation (chest compression or adrenaline administration), an emergency intubation or prolonged stay in intensive care unit
  measure: carbon dioxide partial pressure after the procedure
  time frame: blood sample taken after the procedure (up to 10 minutes)
  description: partial pressure (kPa) of CO2 measured in an arterial blood sample
  arm group label: Arm P
  arm group type: Active Comparator
  description: Patients in arm P will be administered 2-3 mg midazolam i.v. before the beginning of the procedure, 5-10 mcg sufentanil i.v. and a loading dose of propofol 0,8-1,0 mg/kg in 2-5 minutes before the start of the ablation phase. During the procedure, boluses of 0,5 mg/kg propofol will be repeated as needed, in case of inappropriate analgosedation, boluses of midazolam and/or sufentanil can be repeated.
  arm group label: Arm R
  arm group type: Experimental
  description: Patients in arm R will be administered 2,5 mg loading dose of remimazolam followed by continuous infusion at 0,5 mg/h/kg of ideal body weight (IBW, calculated using the Miller formula) and a dose of ketamine 1 mg/kg (ideal body weight) 2-5 minutes before the beginning of the ablation phase. In case of inadequate sedation depth, a bolus of 2,5 mg remimazolam can be repeated as needed. In case the patient shows signs of pain or discomfort, a single dose of ketamine - 0,5 mg/kg IBW - will be administered, followed by a bolus of 5-10 mcg sufentanil if needed. The infusion will be stopped as the last ablation pulses are delivered
  arm group label: Arm TIVA (Total Intravenous Anesthesia)
  arm group type: Experimental
  description: General anaesthesia in patients randomised in arm TIVA will be induced and maintained with a bolus of 10 mcg sufentanil and propofol dosed by TCI system, model Schneider (plasma effect setting). The target plasma concentration for propofol will be set at 5-8 mcg/ml at induction and 4-6 mcg/ml for the rest of the procedure. After the induction, a laryngeal mask (LMA) will be inserted, the patient will be ventilated with 0,3 - 0,4 fraction of inspired oxygen (FiO2), minute ventilation set to achieve end tidal CO2 30 - 40 mmHg. At the beginning of the ablation phase, one bolus of 5-10 mcg sufentanil can be repeated. The dosage of TIVA can be changed so that no sign of discomfort is observed in the patient during ablation pulses. After the last ablation pulse is delivered, infusion of propofol will be ceased and LMA extracted at the return of consciousness.
  intervention type: Drug
  intervention name: Remimazolam
  description: analgosedation without secured airway
  arm group label: Arm R
  intervention type: Drug
  intervention name: Propofol
  description: analgosedation with secured airway
  arm group label: Arm P
  intervention type: Drug
  intervention name: Propofol
  description: TIVA with secured airway
  arm group label: Arm TIVA (Total Intravenous Anesthesia)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Marek Hozman, MD
  phone: +420 267 161 111
  email: marek.hozman@fnkv.cz
  responsible party type: Principal Investigator
  investigator affiliation: Charles University, Czech Republic
  investigator full name: Marek Hozman
  investigator title: Principal investigator
  mesh term: Atrial Fibrillation
  mesh term: Propofol