<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/NCT04487262</url>
  </required_header>
  <id_info>
    <org_study_id>1-10-72-1-20</org_study_id>
    <nct_id>NCT04487262</nct_id>
  </id_info>
  <brief_title>Timing for Removal of Chest Tubes in Adult Cardiac Surgery</brief_title>
  <official_title>Timing for Removal of Chest Tubes in Adult Cardiac Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aarhus University Hospital Skejby</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Aarhus University Hospital Skejby</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale:&#xD;
&#xD;
      Evidence regarding the timing of chest tube removal after cardiac surgery is sparse. The&#xD;
      timing of chest tubes removal constitutes a balancing act between risk of retained blood&#xD;
      syndrome, infection, patient discomfort and opioid-related side effects. Several studies have&#xD;
      shown that chest tubes can safely be removed on the first postoperative day compared to&#xD;
      later. A single retrospective study raised concern as chest tube removal on the day of&#xD;
      surgery was associated with an increased requirement of drainage of pleural effusions.&#xD;
&#xD;
      Primary Objective:&#xD;
&#xD;
      To compare the impact of two standard chest tube removal protocols following open-heart&#xD;
      surgery on the incidence of pleural and/or pericardial effusion requiring invasive drainage&#xD;
&#xD;
      Secondary Objectives&#xD;
&#xD;
      To evaluate the impact of chest tube removal on the day of surgery (DAY0) compared to the&#xD;
      first postoperative day (DAY1) regarding:&#xD;
&#xD;
        -  Comsumption of analgetic drugs&#xD;
&#xD;
        -  Early postoperative pain&#xD;
&#xD;
        -  Incidence of infection&#xD;
&#xD;
        -  Early postoperative respiratory function&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      Single-center, open, parallel-group, prospective, cluster-randomized controlled trial&#xD;
      Alternate assignment of chest tube removal according to Day 0 versus Day 1 protocol based&#xD;
      upon the month of surgery (even versus odd months).&#xD;
&#xD;
      Study population:&#xD;
&#xD;
      1300 consecutive patients undergoing elective open heart surgery in full or lower&#xD;
      hemisternotomy with or without cardiopulmonary bypass including coronary artery bypass&#xD;
      grafting, valve surgery, simple aortic surgery or combinations.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Safety interim analysis&#xD;
  </why_stopped>
  <start_date type="Actual">September 1, 2020</start_date>
  <completion_date type="Actual">October 31, 2021</completion_date>
  <primary_completion_date type="Actual">October 31, 2021</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>Prospective cluster-randomized parallel study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of postoperative pleural and/or pericardial effusion</measure>
    <time_frame>up to 30 days after surgery</time_frame>
    <description>Effusion requiring invasive drainage</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quantity of opiod consumption</measure>
    <time_frame>During 1st, 2nd, 3rd, and 4th postoperative day, and in total after 30 days</time_frame>
    <description>Measured as oral morphine equivalent daily dose (mg/day)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantity of non-steroidal anti-inflammatory drug consumption</measure>
    <time_frame>During 1st, 2nd, 3rd, and 4th postoperative day, and in total after 30 days</time_frame>
    <description>Daily dose of NSAIDs standardized by using the manufacturers' recommended minimum daily maintenance doses for rheumatoid arthritis as 1 dose unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensity of postoperative pain</measure>
    <time_frame>Before and after first mobilization day 1</time_frame>
    <description>Measured as NRS score: Scale 0 (no pain) to 10 (worst possible pain)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of chest tube output</measure>
    <time_frame>after 24 hours and up to removal (max. up to 30 days)</time_frame>
    <description>measured in mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate re-exploration because of bleeding</measure>
    <time_frame>up to 30-day follow-up</time_frame>
    <description>Re-exploration due to haemorrhage or signs of tamponade &lt; 24 hours of surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of re-exploration due to tamponade</measure>
    <time_frame>up to 30-day follow-up</time_frame>
    <description>Re-exploration due to clinical signs of tamponade &gt; 24 hours after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time until chest tube removal</measure>
    <time_frame>In-hospital</time_frame>
    <description>Measured in hours after completed surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay on cardiac surgery intensive care unit</measure>
    <time_frame>In-hospital</time_frame>
    <description>Number of nights</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay after surgery</measure>
    <time_frame>up to 30-day follow-up</time_frame>
    <description>Days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of infection requiring antibiotic treatment:</measure>
    <time_frame>up to 30-day follow-up</time_frame>
    <description>Number of:&#xD;
Superficial wound infection (sternal or saphenous vein harvest site)&#xD;
Deep wound infection (sternal or saphenous vein harvest site)&#xD;
Pneumonia&#xD;
Urinary tract infection&#xD;
Antibiotic treatment for fever of unknown origin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of new-onset atrial fibrillation</measure>
    <time_frame>up to 30-day follow-up</time_frame>
    <description>New-onset postoperative atrial fibrillation requring intervention (drug or defibrillation)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Re-hospitalization due to pleural or pericardial effusion up to 30-day follow-up</measure>
    <time_frame>up to 30-day follow-up</time_frame>
    <description>Number and length of stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of acute kidney injury</measure>
    <time_frame>up to 30-day follow-up</time_frame>
    <description>Classified according to the Acute Kidney Injury Network (AKIN) classification:&#xD;
Stage 1: Creatinine × 1.5 - 2.0 from baseline Stage 2: Creatinine × 2.0-3.0 (i.e. doubled or tripled creatinine) Stage 3: Creatinine &gt; 3.0 x baseline level OR initiation of renal replacement therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of mechanical ventilation</measure>
    <time_frame>In-hospital (max up to 30 days)</time_frame>
    <description>Measured in hours after completed surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Early postoperative respiratory function</measure>
    <time_frame>after first mobilization day 1</time_frame>
    <description>PaO2/FiO2 ratio</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need for supplemental oxygen</measure>
    <time_frame>In-hospital (max up to 30 days)</time_frame>
    <description>Days</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">515</enrollment>
  <condition>Heart Surgery</condition>
  <condition>Chest Tube</condition>
  <condition>Effusion Pleural</condition>
  <condition>Pain, Postoperative</condition>
  <arm_group>
    <arm_group_label>Day O chest tube removal</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Chest tubes maybe removed ten hours after arrival at the intensive care provided standardized removal criteria are fulfilled:&#xD;
blood loss through chest tubes less than 200 ml during the last four hours&#xD;
no air leak&#xD;
the patient extubated and mobilized It remains at the discretion of the attending cardiac surgeon to postpone chest tube removal in cases of increased bleeding risk, due to circumstances which develop during the perioperative period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Day 1 chest tube removal</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Chest tubes are removed in the early morning of the first postoperative day, provided standardized removal criteria are fulfilled:&#xD;
blood loss through chest tubes less than 200 ml during the last four hours&#xD;
no air leak&#xD;
the patient extubated and mobilized It remains at the discretion of both the attending surgeon and anestesiologist to remove chest tubes prematurely in cases of drain-induced, severe analgetic resistant, intractable pain resistant to analgetic treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Cardiac surgery</intervention_name>
    <description>Elective open heart surgery</description>
    <arm_group_label>Day 1 chest tube removal</arm_group_label>
    <arm_group_label>Day O chest tube removal</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All consecutive patients undergoing elective open heart surgery in full or lower&#xD;
        hemisternotomy with or without cardiopulmonary bypass including coronary artery bypass&#xD;
        grafting, valve surgery, simple aortic surgery or combinations.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Cardiac procedures deemed not eligible to chest tube removal on the day of surgery due to&#xD;
        increased bleeding risk due to:&#xD;
&#xD;
          -  Procedures in hypothermic circulatory arrest&#xD;
&#xD;
          -  Previous cardiac surgery&#xD;
&#xD;
          -  Procedures performed through upper hemisternotomy&#xD;
&#xD;
          -  Emergent treatment required (&lt; 24 hours)&#xD;
&#xD;
          -  Non-aspirin antiplatelet drugs stopped &lt; 5 days preoperatively (Clopidogrel,&#xD;
             Prasugrel, Ticagrelor, Ticlopidine)&#xD;
&#xD;
          -  Current use of vitamin K antagonists or new oral non-vitamin K anticoagulants&#xD;
&#xD;
          -  Platelet count &gt; 450 or &lt;100 x 109/l prior to surgery&#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>Ivy Susanne Modrau, MD, dr.med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Consultant Cardiac Surgeon</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dep. of Cardiothoracic Surgery, Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <reference>
    <citation>Andreasen JJ, Sorensen GV, Abrahamsen ER, Hansen-Nord E, Bundgaard K, Bendtsen MD, Troelsen P. Early chest tube removal following cardiac surgery is associated with pleural and/or pericardial effusions requiring invasive treatment. Eur J Cardiothorac Surg. 2016 Jan;49(1):288-92. doi: 10.1093/ejcts/ezv005. Epub 2015 Feb 7.</citation>
    <PMID>25661079</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2020</study_first_posted>
  <last_update_submitted>August 6, 2023</last_update_submitted>
  <last_update_submitted_qc>August 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Aarhus University Hospital Skejby</investigator_affiliation>
    <investigator_full_name>Ivy susanne Modrau, MD</investigator_full_name>
    <investigator_title>Consultant Cardiac Surgeon, Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Surgery, Heart</keyword>
  <keyword>Chest Tube</keyword>
  <keyword>Effusion, Pleural</keyword>
  <keyword>Complications, Postoperative</keyword>
  <keyword>Pain, Postoperative</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual-level deidentified patient data that support the findings of this study, and statistical analysis plan are available upon reasonable request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data will be available beginning immediately and ending five years after article publication.</ipd_time_frame>
    <ipd_access_criteria>Data sharing with other researchers requires a methodologically sound proposal (detailed protocol for the proposed study, information about the funding and resources) and approval by the Danish Data Protection Agency.</ipd_access_criteria>
  </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/NCT04487262
org study id: 1-10-72-1-20
nct id: NCT04487262
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Rationale:

      Evidence regarding the timing of chest tube removal after cardiac surgery is sparse. The
      timing of chest tubes removal constitutes a balancing act between risk of retained blood
      syndrome, infection, patient discomfort and opioid-related side effects. Several studies have
      shown that chest tubes can safely be removed on the first postoperative day compared to
      later. A single retrospective study raised concern as chest tube removal on the day of
      surgery was associated with an increased requirement of drainage of pleural effusions.

      Primary Objective:

      To compare the impact of two standard chest tube removal protocols following open-heart
      surgery on the incidence of pleural and/or pericardial effusion requiring invasive drainage

      Secondary Objectives

      To evaluate the impact of chest tube removal on the day of surgery (DAY0) compared to the
      first postoperative day (DAY1) regarding:

        -  Comsumption of analgetic drugs

        -  Early postoperative pain

        -  Incidence of infection

        -  Early postoperative respiratory function

      Study design:

      Single-center, open, parallel-group, prospective, cluster-randomized controlled trial
      Alternate assignment of chest tube removal according to Day 0 versus Day 1 protocol based
      upon the month of surgery (even versus odd months).

      Study population:

      1300 consecutive patients undergoing elective open heart surgery in full or lower
      hemisternotomy with or without cardiopulmonary bypass including coronary artery bypass
      grafting, valve surgery, simple aortic surgery or combinations.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective cluster-randomized parallel study
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of postoperative pleural and/or pericardial effusion
time frame: up to 30 days after surgery
description: Effusion requiring invasive drainage
measure: Quantity of opiod consumption
time frame: During 1st, 2nd, 3rd, and 4th postoperative day, and in total after 30 days
description: Measured as oral morphine equivalent daily dose (mg/day)
measure: Quantity of non-steroidal anti-inflammatory drug consumption
time frame: During 1st, 2nd, 3rd, and 4th postoperative day, and in total after 30 days
description: Daily dose of NSAIDs standardized by using the manufacturers' recommended minimum daily maintenance doses for rheumatoid arthritis as 1 dose unit
measure: Intensity of postoperative pain
time frame: Before and after first mobilization day 1
description: Measured as NRS score: Scale 0 (no pain) to 10 (worst possible pain)
measure: Amount of chest tube output
time frame: after 24 hours and up to removal (max. up to 30 days)
description: measured in mL
measure: Rate re-exploration because of bleeding
time frame: up to 30-day follow-up
description: Re-exploration due to haemorrhage or signs of tamponade < 24 hours of surgery
measure: Number of re-exploration due to tamponade
time frame: up to 30-day follow-up
description: Re-exploration due to clinical signs of tamponade > 24 hours after surgery
measure: Time until chest tube removal
time frame: In-hospital
description: Measured in hours after completed surgery
measure: Length of stay on cardiac surgery intensive care unit
time frame: In-hospital
description: Number of nights
measure: Length of hospital stay after surgery
time frame: up to 30-day follow-up
description: Days
measure: Rate of infection requiring antibiotic treatment:
time frame: up to 30-day follow-up
description: Number of:
Superficial wound infection (sternal or saphenous vein harvest site)
Deep wound infection (sternal or saphenous vein harvest site)
Pneumonia
Urinary tract infection
Antibiotic treatment for fever of unknown origin.
measure: Rate of new-onset atrial fibrillation
time frame: up to 30-day follow-up
description: New-onset postoperative atrial fibrillation requring intervention (drug or defibrillation)
measure: Re-hospitalization due to pleural or pericardial effusion up to 30-day follow-up
time frame: up to 30-day follow-up
description: Number and length of stay
measure: Rate of acute kidney injury
time frame: up to 30-day follow-up
description: Classified according to the Acute Kidney Injury Network (AKIN) classification:
Stage 1: Creatinine × 1.5 - 2.0 from baseline Stage 2: Creatinine × 2.0-3.0 (i.e. doubled or tripled creatinine) Stage 3: Creatinine > 3.0 x baseline level OR initiation of renal replacement therapy
measure: Duration of mechanical ventilation
time frame: In-hospital (max up to 30 days)
description: Measured in hours after completed surgery
measure: Early postoperative respiratory function
time frame: after first mobilization day 1
description: PaO2/FiO2 ratio
measure: Need for supplemental oxygen
time frame: In-hospital (max up to 30 days)
description: Days
arm group label: Day O chest tube removal
arm group type: Active Comparator
description: Chest tubes maybe removed ten hours after arrival at the intensive care provided standardized removal criteria are fulfilled:
blood loss through chest tubes less than 200 ml during the last four hours
no air leak
the patient extubated and mobilized It remains at the discretion of the attending cardiac surgeon to postpone chest tube removal in cases of increased bleeding risk, due to circumstances which develop during the perioperative period
arm group label: Day 1 chest tube removal
arm group type: Active Comparator
description: Chest tubes are removed in the early morning of the first postoperative day, provided standardized removal criteria are fulfilled:
blood loss through chest tubes less than 200 ml during the last four hours
no air leak
the patient extubated and mobilized It remains at the discretion of both the attending surgeon and anestesiologist to remove chest tubes prematurely in cases of drain-induced, severe analgetic resistant, intractable pain resistant to analgetic treatment.
intervention type: Procedure
intervention name: Cardiac surgery
description: Elective open heart surgery
arm group label: Day 1 chest tube removal
arm group label: Day O chest tube removal
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ivy Susanne Modrau, MD, dr.med.
role: Principal Investigator
affiliation: Consultant Cardiac Surgeon
facility: 
country: Denmark
citation: Andreasen JJ, Sorensen GV, Abrahamsen ER, Hansen-Nord E, Bundgaard K, Bendtsen MD, Troelsen P. Early chest tube removal following cardiac surgery is associated with pleural and/or pericardial effusions requiring invasive treatment. Eur J Cardiothorac Surg. 2016 Jan;49(1):288-92. doi: 10.1093/ejcts/ezv005. Epub 2015 Feb 7.
PMID: 25661079
responsible party type: Principal Investigator
investigator affiliation: Aarhus University Hospital Skejby
investigator full name: Ivy susanne Modrau, MD
investigator title: Consultant Cardiac Surgeon, Associate Professor
mesh term: Pain, Postoperative
sharing ipd: Yes
ipd description: Individual-level deidentified patient data that support the findings of this study, and statistical analysis plan are available upon reasonable request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data will be available beginning immediately and ending five years after article publication.
ipd access criteria: Data sharing with other researchers requires a methodologically sound proposal (detailed protocol for the proposed study, information about the funding and resources) and approval by the Danish Data Protection Agency.