<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/NCT03752931</url>
  </required_header>
  <id_info>
    <org_study_id>MAMICELDIL</org_study_id>
    <nct_id>NCT03752931</nct_id>
  </id_info>
  <brief_title>Celiprolol Versus Ditiazem for the Prevention of Postoperative Cardiac Arrythmias in Thoracic Surgery</brief_title>
  <acronym>CelDilPreCA</acronym>
  <official_title>Prevention of Postoperative Cardiac Arrythmias in Thoracic Surgery : Celiprolol Versus Diltiazem</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Abderrahmane Mami Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Abderrahmane Mami Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</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>
      Cardiac arrythmias are the most common cardiac complications after thoracic surgery. They are&#xD;
      made primarily of postoperative atrial fibrillation (POAF).&#xD;
&#xD;
      They are associated with an increased risk of stroke, increased length of hospital stay and&#xD;
      cost of care, and increased long-term mortality.&#xD;
&#xD;
      Randomized , single-blind prospective study in the anesthesia and intensive care department&#xD;
      of Abderrahmen Mami hospital Ariana Tunisia comparing the efficacy of Diltiazem versus&#xD;
      Celiprolol in the prevention of postoperative cardiac arrythmias in patients proposed for&#xD;
      pneumonectomy and bilobectomy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cardiac arrythmias are the most common cardiac complications after thoracic surgery. They are&#xD;
      made primarily of postoperative atrial fibrillation (POAF).&#xD;
&#xD;
      They are associated with an increased risk of stroke, increased length of hospital stay and&#xD;
      cost of care, and increased long-term mortality.&#xD;
&#xD;
      According to the American Association of Thoracic Surgery (AATS), interventions at high risk&#xD;
      for FAPO (&gt; 15%) are: anterior mediastinal mass resection, thoracoscopic lobectomy,&#xD;
      thoracotomy lobectomy, pneumonectomy, pleurectomy, tracheal resection, emphysema bubble,&#xD;
      bronchopleural fistula repair, lung transplantation and oesophagectomy. And it has been shown&#xD;
      that the occurrence of postoperative atrial fibrillation is correlated with the extent of&#xD;
      resection in case of lung resection surgery such as lobectomy or pneumonectomy.&#xD;
&#xD;
      Based on their multifactorial etiology, different pharmacological classes have been used for&#xD;
      the prevention of POAF with varying degrees of success such as Amiodarone, Digoxin, Flecaine,&#xD;
      Magnesium Sulfate, Beta Blockers, Calcium Inhibitors and Statins.&#xD;
&#xD;
      Recommendations were made for the prevention of POAF by the Society of Thoracic Surgeons&#xD;
      (STS) in 2011 and the AATS in 2014 and concluded that Diltiazem is recommended for prevention&#xD;
      and it is a Grade IIA for recommendations of 2011 and a grade IIB for the 2014&#xD;
      recommendations. Beta-blockers (BB) are recommended and it is a grade IIB for the 2011&#xD;
      recommendations. In addition, amiodarone is not recommended in case of pneumonectomy because&#xD;
      of of its pulmonary toxicity for the 2011 recommendations and is ranked grade IIA for the&#xD;
      2014 recommendations.&#xD;
&#xD;
      A meta-analysis published in Chest in 2017 involving 22 studies and 2891 patients showed that&#xD;
      the pharmacological prevention of postoperative rhythm disorders after thoracic surgery&#xD;
      decreases their incidence but does not reduce mortality in the short term. Several drugs have&#xD;
      been studied. Betablockers have the probability of being the most effective agent. Calcium&#xD;
      inhibitors are less effective.&#xD;
&#xD;
      In view of these conflicting results and in the absence of a large randomized controlled&#xD;
      trial comparing two pharmacologic agents for the prevention of POAF, a certain degree of&#xD;
      uncertainty persists regarding the superiority of one agent over another. especially in case&#xD;
      of pulmonary resection surgery. Most studies compare drugs versus placebo. Among these drugs&#xD;
      Diltiazem and BB are among the most effective and safe.&#xD;
&#xD;
      Randomized , single-blind prospective study in the anesthesia and chest surgery departments&#xD;
      of Abderrahmen Mami hospital Ariana Tunisia.&#xD;
&#xD;
      The objective is to compare the efficacy of Celiprolol -Class II of cardioselective&#xD;
      anti-arrhythmic B1 with B2 agonist activity with intrinsic sympathomimetic activity- versus&#xD;
      Diltiazem -Class IV antiarrhythmic calcium antagonist with direct cardiac effects- in the&#xD;
      prevention of cardiac arrhythmias after thoracic surgery such as bilobectomy and&#xD;
      pneumonectomy.&#xD;
&#xD;
      Have been included:&#xD;
&#xD;
        -  Age ≥ 18 years&#xD;
&#xD;
        -  Sinus rhythm preoperatively.&#xD;
&#xD;
        -  Surgery at high risk of atrial arrhythmia occurring postoperatively:&#xD;
&#xD;
      Bi-lobectomy Pneumonectomy&#xD;
&#xD;
      Have not been included:&#xD;
&#xD;
        -  history of cardiac arrhythmia.&#xD;
&#xD;
        -  A prior history of atrio-ventricular block with non-paired degrees II or III.&#xD;
&#xD;
        -  Patients on calcium channel blockers or beta-blockers as background therapy.&#xD;
&#xD;
        -  Hypersensitivity to Diltiazem and / or Celiprolol and / or any of the excipients.&#xD;
&#xD;
        -  Renal insufficiency with creatinine clearance &lt;40 ml / min.&#xD;
&#xD;
        -  wolf parkinson white syndrome.&#xD;
&#xD;
        -  Myasthenia gravis.&#xD;
&#xD;
        -  Chronic Obstructive Pulmonary Disease: GOLD III or IV.&#xD;
&#xD;
      Have been excluded :&#xD;
&#xD;
      • Signs of myocardial ischemia per or post operative.&#xD;
&#xD;
      • Persistent postoperative hypotension requiring the use of catecholamines.&#xD;
&#xD;
        -  Persistent bradycardia.&#xD;
&#xD;
        -  Decompensated cardiac insufficiency.&#xD;
&#xD;
        -  Acute bowel obstruction.&#xD;
&#xD;
           * The main criterion of judgment:&#xD;
&#xD;
        -  Incidence of early postoperative atrial fibrillation.&#xD;
&#xD;
           * Secondary criteria for judgment:&#xD;
&#xD;
        -  The incidence of late arrhythmia (&gt; 14 days) during or after hospitalization during the&#xD;
           30 postoperative days.&#xD;
&#xD;
        -  The incidence of other rhythm disorders.&#xD;
&#xD;
        -  The duration of the arrhythmia in case of occurrence.&#xD;
&#xD;
        -  Length of stay in intensive care unit and hospital.&#xD;
&#xD;
        -  30-day mortality.&#xD;
&#xD;
        -  Other complications during 14 days postoperative:&#xD;
&#xD;
      Pulmonary: Atelectasis, pneumonitis, ARDS, Cardiovascular: heart failure, heart attack,&#xD;
      pulmonary embolism. Neurological: stroke Acute renal failure. • Product Tolerance: Digestive&#xD;
      Disorders, Dizziness, Bradycardia, Hypotension, Bronchospasm, Hypoglycemia or Hyperglycemia.&#xD;
&#xD;
      * Perioperative management:&#xD;
&#xD;
      - Preoperatively:&#xD;
&#xD;
      All patients are assessed at the pre-anesthetic consultation. All patients are informed about&#xD;
      postoperative treatment to reduce the incidence of arrhythmias.&#xD;
&#xD;
      A consent form is signed for this purpose.&#xD;
&#xD;
        -  Inoperative:&#xD;
&#xD;
        -  General anaesthesia:&#xD;
&#xD;
      Induction: Fentanyl, Propofol, Cisatracurium Maintenance: Propofol to push electric syringe,&#xD;
      fentanyl and cisatracurium.&#xD;
&#xD;
        -  Perioperative fluid restriction &lt;25ml / kg / 24h with isotonic saline as much as&#xD;
           possible.&#xD;
&#xD;
        -  The extent of pericardial resection and mediastinal lymph node dissection are mentioned.&#xD;
&#xD;
        -  Bleeding estimated peroperatively, the need for catecholamines, labile blood products&#xD;
           and intraoperative incidents are noted.&#xD;
&#xD;
        -  Postoperative analgesia combines Paracetamol 1g per 6 hours with thoracic epidural&#xD;
           analgesia or multimodal analgesia with morphine titration as needed.&#xD;
&#xD;
      Postoperatively:&#xD;
&#xD;
      - All patients are admitted to intensive care.&#xD;
&#xD;
        -  Close monitoring of hemodynamic, respiratory and neurological parameters.&#xD;
&#xD;
        -  Patients are randomized into 2 groups:&#xD;
&#xD;
      Group 1: receiving 1 tablet per day of celiprolol 200 mg in the morning from the first day&#xD;
      after surgery.&#xD;
&#xD;
      Group 2: receiving 1 capsule per day of diltiazem 200 mg in the morning from the first&#xD;
      postoperative day.&#xD;
&#xD;
      The target heart rate is between 70 and 80 bpm by titrating the antiarrhythmic agent.&#xD;
&#xD;
      The treatment will be continued for 14 days.&#xD;
&#xD;
        -  electrocardiogram at 6 hours postoperative or if clinical suspicion of arrhythmia or&#xD;
           modification to the scope then twice a day.&#xD;
&#xD;
        -  Postoperative blood count.&#xD;
&#xD;
        -  Magnesemia, phosphoremia, calcemia, and blood ionogram at the first postoperative day&#xD;
           and correction if abnormalities.&#xD;
&#xD;
        -  X-ray of the postoperative chest and 1 time per day especially for the research of&#xD;
           deviation of the mediastinum in case of pneumonectomy.&#xD;
&#xD;
      The occurrence of an arrhythmia will be treated according to the following algorithm:&#xD;
&#xD;
        -  Look for probable cause of bleeding, pulmonary embolism, pneumothorax, pericardial&#xD;
           effusion, mediastinal deviation, hypoxia, myocardial ischemia or sepsis.&#xD;
&#xD;
        -  Optimize the volemia.&#xD;
&#xD;
        -  Correct metabolic disorders.&#xD;
&#xD;
        -  Optimize analgesia.&#xD;
&#xD;
        -  If hemodynamically unstable:&#xD;
&#xD;
      Of duration &lt;48 h: external electric shock and advice cardiology. Duration&gt; 48 h: consider&#xD;
      anticoagulation, external electrical shock and cardiology.&#xD;
&#xD;
      -It is hemodynamically stable&#xD;
&#xD;
      Duration &lt;48h:&#xD;
&#xD;
      Consider anticoagulation if CHA2DS2 score VASc&gt; 1, amiodarone IV then per os and notice&#xD;
      cardiology.&#xD;
&#xD;
      Duration&gt; 48h: consider anticoagulation, IV amiodarone then per os and opinion cardiology.&#xD;
&#xD;
      • All patients are referred to outpatient cardiology consultations with a rhythmic holter&#xD;
      upon discharge.&#xD;
&#xD;
      The occurrence of another postoperative complication will be noted by specifying the date of&#xD;
      occurrence in relation to the arrhythmia:&#xD;
&#xD;
        -  Pulmonary: Atelectasis, pneumonitis, ARDS, need for prolonged mechanical ventilation.&#xD;
&#xD;
        -  Cardiovascular: heart failure, myocardial infarction, pulmonary embolism.&#xD;
&#xD;
        -  Neurological: Stroke&#xD;
&#xD;
        -  Acute renal failure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">December 2018</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>incidence of early postoperative atrial fibrillation</measure>
    <time_frame>14 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>incidence of other cardiac arrythmias and other complications</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Postoperative Cardiac Complication</condition>
  <arm_group>
    <arm_group_label>Celiprolol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>receiving 1 tablet per day of celiprolol (Celiprol®) 200 mg in the morning from the first postoperative day after pneumonectomy or bi lobecomty for 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diltiazem</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>receiving 1 capsule per day of diltiazem (Monotildiem® LP) 200 mg in the morning from the first postoperative day after pneumonectomy or bi lobectomy for 2 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Celiprolol</intervention_name>
    <description>receiving 1 tablet per day of Celiprolol 200 mg in the morning from the first postoperative day after pneumonectomy or bi lobecomty for 2 weeks.</description>
    <arm_group_label>Celiprolol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Diltiazem</intervention_name>
    <description>receiving 1 tablet per day of Diltiazem 200 mg in the morning from the first postoperative day after pneumonectomy or bi lobecomty for 2 weeks.</description>
    <arm_group_label>Diltiazem</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years Sinus rhythm preoperatively.&#xD;
&#xD;
        Surgery at high risk of atrial arrhythmia occurring postoperatively:&#xD;
&#xD;
          -  Bi-lobectomy&#xD;
&#xD;
          -  Pneumonectomie&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Signs of myocardial ischemia per or post operative.&#xD;
&#xD;
          -  Persistent postoperative hypotension requiring the use of catecholamines.&#xD;
&#xD;
          -  Persistent bradycardia&#xD;
&#xD;
          -  Decompensated cardiac insufficiency.&#xD;
&#xD;
          -  Acute intestinal obstruction.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marzouk Mahmoud, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Abderrahmane Mami Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>MARZOUK Mahmoud, MD</last_name>
    <phone>0021620874718</phone>
    <email>mahmoudmarzouk@hotmail.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>OUERGHI Sonia, MD</last_name>
    <email>ouerghisonia09@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hospital Abderrahmane Mami</name>
      <address>
        <city>Ariana</city>
        <country>Tunisia</country>
      </address>
    </facility>
    <contact>
      <last_name>Marzouk Mahmoud, MD</last_name>
      <phone>0021620874718</phone>
      <email>mahmoudmarzouk@hotmail.Fr</email>
    </contact>
  </location>
  <location_countries>
    <country>Tunisia</country>
  </location_countries>
  <reference>
    <citation>Zhao BC, Huang TY, Deng QW, Liu WF, Liu J, Deng WT, Liu KX, Li C. Prophylaxis Against Atrial Fibrillation After General Thoracic Surgery: Trial Sequential Analysis and Network Meta-Analysis. Chest. 2017 Jan;151(1):149-159. doi: 10.1016/j.chest.2016.08.1476. Epub 2016 Oct 8.</citation>
    <PMID>27729264</PMID>
  </reference>
  <reference>
    <citation>Fernando HC, Jaklitsch MT, Walsh GL, Tisdale JE, Bridges CD, Mitchell JD, Shrager JB. The Society of Thoracic Surgeons practice guideline on the prophylaxis and management of atrial fibrillation associated with general thoracic surgery: executive summary. Ann Thorac Surg. 2011 Sep;92(3):1144-52. doi: 10.1016/j.athoracsur.2011.06.104. No abstract available.</citation>
    <PMID>21871327</PMID>
  </reference>
  <reference>
    <citation>Frendl G, Sodickson AC, Chung MK, Waldo AL, Gersh BJ, Tisdale JE, Calkins H, Aranki S, Kaneko T, Cassivi S, Smith SC Jr, Darbar D, Wee JO, Waddell TK, Amar D, Adler D; American Association for Thoracic Surgery. 2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures. J Thorac Cardiovasc Surg. 2014 Sep;148(3):e153-93. doi: 10.1016/j.jtcvs.2014.06.036. Epub 2014 Jun 30. No abstract available.</citation>
    <PMID>25129609</PMID>
  </reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 21, 2018</study_first_submitted>
  <study_first_submitted_qc>November 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 26, 2018</study_first_posted>
  <last_update_submitted>November 22, 2018</last_update_submitted>
  <last_update_submitted_qc>November 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Abderrahmane Mami Hospital</investigator_affiliation>
    <investigator_full_name>MahmoudMARZOUK</investigator_full_name>
    <investigator_title>Medical Doctor anesthesiology and intensive care</investigator_title>
  </responsible_party>
  <keyword>Pneumonectomy Thoracic surgery Celiprolol Diltiazem</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arrhythmias, Cardiac</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Celiprolol</mesh_term>
    <mesh_term>Diltiazem</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/NCT03752931
org study id: MAMICELDIL
nct id: NCT03752931
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
Cardiac arrythmias are the most common cardiac complications after thoracic surgery. They are
      made primarily of postoperative atrial fibrillation (POAF).

      They are associated with an increased risk of stroke, increased length of hospital stay and
      cost of care, and increased long-term mortality.

      Randomized , single-blind prospective study in the anesthesia and intensive care department
      of Abderrahmen Mami hospital Ariana Tunisia comparing the efficacy of Diltiazem versus
      Celiprolol in the prevention of postoperative cardiac arrythmias in patients proposed for
      pneumonectomy and bilobectomy.
Cardiac arrythmias are the most common cardiac complications after thoracic surgery. They are
      made primarily of postoperative atrial fibrillation (POAF).

      They are associated with an increased risk of stroke, increased length of hospital stay and
      cost of care, and increased long-term mortality.

      According to the American Association of Thoracic Surgery (AATS), interventions at high risk
      for FAPO (> 15%) are: anterior mediastinal mass resection, thoracoscopic lobectomy,
      thoracotomy lobectomy, pneumonectomy, pleurectomy, tracheal resection, emphysema bubble,
      bronchopleural fistula repair, lung transplantation and oesophagectomy. And it has been shown
      that the occurrence of postoperative atrial fibrillation is correlated with the extent of
      resection in case of lung resection surgery such as lobectomy or pneumonectomy.

      Based on their multifactorial etiology, different pharmacological classes have been used for
      the prevention of POAF with varying degrees of success such as Amiodarone, Digoxin, Flecaine,
      Magnesium Sulfate, Beta Blockers, Calcium Inhibitors and Statins.

      Recommendations were made for the prevention of POAF by the Society of Thoracic Surgeons
      (STS) in 2011 and the AATS in 2014 and concluded that Diltiazem is recommended for prevention
      and it is a Grade IIA for recommendations of 2011 and a grade IIB for the 2014
      recommendations. Beta-blockers (BB) are recommended and it is a grade IIB for the 2011
      recommendations. In addition, amiodarone is not recommended in case of pneumonectomy because
      of of its pulmonary toxicity for the 2011 recommendations and is ranked grade IIA for the
      2014 recommendations.

      A meta-analysis published in Chest in 2017 involving 22 studies and 2891 patients showed that
      the pharmacological prevention of postoperative rhythm disorders after thoracic surgery
      decreases their incidence but does not reduce mortality in the short term. Several drugs have
      been studied. Betablockers have the probability of being the most effective agent. Calcium
      inhibitors are less effective.

      In view of these conflicting results and in the absence of a large randomized controlled
      trial comparing two pharmacologic agents for the prevention of POAF, a certain degree of
      uncertainty persists regarding the superiority of one agent over another. especially in case
      of pulmonary resection surgery. Most studies compare drugs versus placebo. Among these drugs
      Diltiazem and BB are among the most effective and safe.

      Randomized , single-blind prospective study in the anesthesia and chest surgery departments
      of Abderrahmen Mami hospital Ariana Tunisia.

      The objective is to compare the efficacy of Celiprolol -Class II of cardioselective
      anti-arrhythmic B1 with B2 agonist activity with intrinsic sympathomimetic activity- versus
      Diltiazem -Class IV antiarrhythmic calcium antagonist with direct cardiac effects- in the
      prevention of cardiac arrhythmias after thoracic surgery such as bilobectomy and
      pneumonectomy.

      Have been included:

        -  Age ≥ 18 years

        -  Sinus rhythm preoperatively.

        -  Surgery at high risk of atrial arrhythmia occurring postoperatively:

      Bi-lobectomy Pneumonectomy

      Have not been included:

        -  history of cardiac arrhythmia.

        -  A prior history of atrio-ventricular block with non-paired degrees II or III.

        -  Patients on calcium channel blockers or beta-blockers as background therapy.

        -  Hypersensitivity to Diltiazem and / or Celiprolol and / or any of the excipients.

        -  Renal insufficiency with creatinine clearance <40 ml / min.

        -  wolf parkinson white syndrome.

        -  Myasthenia gravis.

        -  Chronic Obstructive Pulmonary Disease: GOLD III or IV.

      Have been excluded :

      • Signs of myocardial ischemia per or post operative.

      • Persistent postoperative hypotension requiring the use of catecholamines.

        -  Persistent bradycardia.

        -  Decompensated cardiac insufficiency.

        -  Acute bowel obstruction.

           * The main criterion of judgment:

        -  Incidence of early postoperative atrial fibrillation.

           * Secondary criteria for judgment:

        -  The incidence of late arrhythmia (> 14 days) during or after hospitalization during the
           30 postoperative days.

        -  The incidence of other rhythm disorders.

        -  The duration of the arrhythmia in case of occurrence.

        -  Length of stay in intensive care unit and hospital.

        -  30-day mortality.

        -  Other complications during 14 days postoperative:

      Pulmonary: Atelectasis, pneumonitis, ARDS, Cardiovascular: heart failure, heart attack,
      pulmonary embolism. Neurological: stroke Acute renal failure. • Product Tolerance: Digestive
      Disorders, Dizziness, Bradycardia, Hypotension, Bronchospasm, Hypoglycemia or Hyperglycemia.

      * Perioperative management:

      - Preoperatively:

      All patients are assessed at the pre-anesthetic consultation. All patients are informed about
      postoperative treatment to reduce the incidence of arrhythmias.

      A consent form is signed for this purpose.

        -  Inoperative:

        -  General anaesthesia:

      Induction: Fentanyl, Propofol, Cisatracurium Maintenance: Propofol to push electric syringe,
      fentanyl and cisatracurium.

        -  Perioperative fluid restriction <25ml / kg / 24h with isotonic saline as much as
           possible.

        -  The extent of pericardial resection and mediastinal lymph node dissection are mentioned.

        -  Bleeding estimated peroperatively, the need for catecholamines, labile blood products
           and intraoperative incidents are noted.

        -  Postoperative analgesia combines Paracetamol 1g per 6 hours with thoracic epidural
           analgesia or multimodal analgesia with morphine titration as needed.

      Postoperatively:

      - All patients are admitted to intensive care.

        -  Close monitoring of hemodynamic, respiratory and neurological parameters.

        -  Patients are randomized into 2 groups:

      Group 1: receiving 1 tablet per day of celiprolol 200 mg in the morning from the first day
      after surgery.

      Group 2: receiving 1 capsule per day of diltiazem 200 mg in the morning from the first
      postoperative day.

      The target heart rate is between 70 and 80 bpm by titrating the antiarrhythmic agent.

      The treatment will be continued for 14 days.

        -  electrocardiogram at 6 hours postoperative or if clinical suspicion of arrhythmia or
           modification to the scope then twice a day.

        -  Postoperative blood count.

        -  Magnesemia, phosphoremia, calcemia, and blood ionogram at the first postoperative day
           and correction if abnormalities.

        -  X-ray of the postoperative chest and 1 time per day especially for the research of
           deviation of the mediastinum in case of pneumonectomy.

      The occurrence of an arrhythmia will be treated according to the following algorithm:

        -  Look for probable cause of bleeding, pulmonary embolism, pneumothorax, pericardial
           effusion, mediastinal deviation, hypoxia, myocardial ischemia or sepsis.

        -  Optimize the volemia.

        -  Correct metabolic disorders.

        -  Optimize analgesia.

        -  If hemodynamically unstable:

      Of duration <48 h: external electric shock and advice cardiology. Duration> 48 h: consider
      anticoagulation, external electrical shock and cardiology.

      -It is hemodynamically stable

      Duration <48h:

      Consider anticoagulation if CHA2DS2 score VASc> 1, amiodarone IV then per os and notice
      cardiology.

      Duration> 48h: consider anticoagulation, IV amiodarone then per os and opinion cardiology.

      • All patients are referred to outpatient cardiology consultations with a rhythmic holter
      upon discharge.

      The occurrence of another postoperative complication will be noted by specifying the date of
      occurrence in relation to the arrhythmia:

        -  Pulmonary: Atelectasis, pneumonitis, ARDS, need for prolonged mechanical ventilation.

        -  Cardiovascular: heart failure, myocardial infarction, pulmonary embolism.

        -  Neurological: Stroke

        -  Acute renal failure.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Prevention
masking: Single (Outcomes Assessor)
measure: incidence of early postoperative atrial fibrillation
time frame: 14 days
measure: incidence of other cardiac arrythmias and other complications
time frame: 30 days
arm group label: Celiprolol
arm group type: Active Comparator
description: receiving 1 tablet per day of celiprolol (Celiprol®) 200 mg in the morning from the first postoperative day after pneumonectomy or bi lobecomty for 2 weeks.
arm group label: Diltiazem
arm group type: Active Comparator
description: receiving 1 capsule per day of diltiazem (Monotildiem® LP) 200 mg in the morning from the first postoperative day after pneumonectomy or bi lobectomy for 2 weeks.
intervention type: Drug
intervention name: Celiprolol
description: receiving 1 tablet per day of Celiprolol 200 mg in the morning from the first postoperative day after pneumonectomy or bi lobecomty for 2 weeks.
arm group label: Celiprolol
intervention type: Drug
intervention name: Diltiazem
description: receiving 1 tablet per day of Diltiazem 200 mg in the morning from the first postoperative day after pneumonectomy or bi lobecomty for 2 weeks.
arm group label: Diltiazem
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Marzouk Mahmoud, MD
role: Principal Investigator
affiliation: Abderrahmane Mami Hospital
last name: MARZOUK Mahmoud, MD
phone: 0021620874718
email: mahmoudmarzouk@hotmail.fr
last name: OUERGHI Sonia, MD
email: ouerghisonia09@gmail.com
facility: 
contact: 
country: Tunisia
citation: Zhao BC, Huang TY, Deng QW, Liu WF, Liu J, Deng WT, Liu KX, Li C. Prophylaxis Against Atrial Fibrillation After General Thoracic Surgery: Trial Sequential Analysis and Network Meta-Analysis. Chest. 2017 Jan;151(1):149-159. doi: 10.1016/j.chest.2016.08.1476. Epub 2016 Oct 8.
PMID: 27729264
citation: Fernando HC, Jaklitsch MT, Walsh GL, Tisdale JE, Bridges CD, Mitchell JD, Shrager JB. The Society of Thoracic Surgeons practice guideline on the prophylaxis and management of atrial fibrillation associated with general thoracic surgery: executive summary. Ann Thorac Surg. 2011 Sep;92(3):1144-52. doi: 10.1016/j.athoracsur.2011.06.104. No abstract available.
PMID: 21871327
citation: Frendl G, Sodickson AC, Chung MK, Waldo AL, Gersh BJ, Tisdale JE, Calkins H, Aranki S, Kaneko T, Cassivi S, Smith SC Jr, Darbar D, Wee JO, Waddell TK, Amar D, Adler D; American Association for Thoracic Surgery. 2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures. J Thorac Cardiovasc Surg. 2014 Sep;148(3):e153-93. doi: 10.1016/j.jtcvs.2014.06.036. Epub 2014 Jun 30. No abstract available.
PMID: 25129609
responsible party type: Principal Investigator
investigator affiliation: Abderrahmane Mami Hospital
investigator full name: MahmoudMARZOUK
investigator title: Medical Doctor anesthesiology and intensive care
mesh term: Arrhythmias, Cardiac
mesh term: Celiprolol
mesh term: Diltiazem
sharing ipd: No