<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/NCT04436016</url>
  </required_header>
  <id_info>
    <org_study_id>PROTECTIN Pilot</org_study_id>
    <secondary_id>SNCTP000003728</secondary_id>
    <nct_id>NCT04436016</nct_id>
  </id_info>
  <brief_title>PeRiOperaTivE CardioproTection With Ivabradine in Non-cardiac Surgery</brief_title>
  <acronym>PROTECTIN</acronym>
  <official_title>Effect of Heart Rate Control With Ivabradine on Myocardial Injury After Non-cardiac Surgery: a Single Center, Randomized Controlled, Double-blind Feasibility Pilot Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Geneva</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Geneva</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>
      Perioperative myocardial injury (PMI) after non-cardiac surgery (NCS), i.e. the elevation of&#xD;
      postoperative troponin, occurs in nearly 20% of patients older than 45 years undergoing NCS&#xD;
      and is independently and strongly associated with post-operative mortality (30-day mortality&#xD;
      up to 10%). With over 300 million surgical interventions every year worldwide, PMI has a high&#xD;
      clinical relevance on the health of the population.&#xD;
&#xD;
      Heart rate (HR) is an independent and modifiable risk factor for PMI and death after&#xD;
      non-cardiac surgery. Numerous studies showed that beta-blockers decrease myocardial ischemia&#xD;
      after surgery in a heart-rate dependent manner, but this beneficial effect is surpassed by an&#xD;
      increased incidence of perioperative hypotension and death. Currently, no single intervention&#xD;
      is available to decrease the risk of perioperative cardiac complications. Ivabradine (IVA) is&#xD;
      a negative chronotropic agent without significant effects on contractility or vascular tone&#xD;
      and has been shown to improve outcomes in the setting of chronic and acute heart diseases.&#xD;
&#xD;
      Rationale for pilot feasibility trial: the planned definitive large trial is a multicenter&#xD;
      trial to investigate the efficacy of ivabradine to decrease perioperative myocardial injury.&#xD;
      The intervention planned is complex and demands important resources. The investigators&#xD;
      designed this pilot study to inform on the feasibility of the definitive large trial. This&#xD;
      pilot study will also provide additional information that could help investigators improve&#xD;
      the definitive large trial regarding recruitment, refinements to the study protocol and&#xD;
      improving the participant's experience.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 5, 2020</start_date>
  <completion_date type="Actual">January 11, 2022</completion_date>
  <primary_completion_date type="Actual">December 12, 2021</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>Single center, randomized, placebo-controlled, double-blind, parallel group, feasibility pilot trial.&#xD;
Patients will be randomized to receive ivabradine or placebo.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Appropriate dosage rate</measure>
    <time_frame>From the morning (6-9 am) of the day of surgery of the first study participant to the evening of the second post-operative day of the last study participant (up to 1 year from first randomization).</time_frame>
    <description>Number of correct dosages administered according to the patient's heart rate at each study visit divided by the total dosages administrated</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blinding success rate</measure>
    <time_frame>From the morning (6-9 am) of the day of surgery of the first study participant to the evening of the second post-operative day of the last study participant (up to 1 year from first randomization).</time_frame>
    <description>Number of times blinding code was broken divided by the total dosages administrated</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recruitment rate</measure>
    <time_frame>Up to one year from the date participant screening begins.</time_frame>
    <description>Total number of eligible participants approached, the number recruited and randomised divided by the number of months that the trial recruited for</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant satisfaction regarding information about the study, informed consent, recruitment procedures and study participation</measure>
    <time_frame>Screening, morning of the day surgery pre-operatively and post-operative days 1, 2 and 3.</time_frame>
    <description>Qualitative research methods (shadowing and semi-structured interviews)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perioperative myocardial injury</measure>
    <time_frame>Day of surgery pre-operatively (between 6-9 am) and post-operatively (between 6-9 pm or within 1h after surgery if surgery ends after 9pm) and morning (between 6-9 am) of post-operative days 1, 2, 3 and day of hospital discharge.</time_frame>
    <description>Variance of high-sensitive cardiac troponin T (ng/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>Day of surgery pre-operatively (between 6-9 am) and post-operatively (between 6-9 pm or within 1h after surgery if surgery ends after 9pm) and morning (between 6-9 am) of post-operative days 1, 2, 3 and day of hospital discharge.</time_frame>
    <description>Variance of resting heart rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ivabradine dosage</measure>
    <time_frame>Day of surgery pre-operatively (between 6-9 am) and morning (between 6-9 am) of post-operative days 1 and 2.</time_frame>
    <description>Variance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Recovery</measure>
    <time_frame>Morning (between 6-9 am) of post-operative days 1, 3 and at day of hospital discharge.</time_frame>
    <description>Variance of Quality of Recovery assessed with Quality of Recovery-15 scale (range from 0 to 150, with higher scores indicating a better outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difficulty in following study protocol and administrating study drug</measure>
    <time_frame>Morning (between 6 and 9 am) and evening (between 6 and 9 pm) of day of sugery and post-operative days 1 and 2.</time_frame>
    <description>4-point Likert scale (Study personnel will be asked &quot;The decision to administer the study drug according to the patient's heart rate was straightforward&quot;. Answers range from Strongly agree, Agree, Disagree to Strongly disagree)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Bradycardia</measure>
    <time_frame>From the morning of the day of surgery when the first study intervention (between 6-9am) is adminitstered until post-operative day 3 in the morning (between 6-9am).</time_frame>
    <description>Number of patients with those with a heart rate &lt;50 or requiring an intervention to increase heart rate as atropine</description>
  </other_outcome>
  <other_outcome>
    <measure>Atrial fibrilation</measure>
    <time_frame>From the morning of the day of surgery when the first study intervention (between 6-9am) is adminitstered until post-operative day 3 in the morning (between 6-9am).</time_frame>
    <description>Number of patients with atrial fibrilation</description>
  </other_outcome>
  <other_outcome>
    <measure>Phosphenes</measure>
    <time_frame>From the morning of the day of surgery when the first study intervention (between 6-9am) is adminitstered until post-operative day 3 in the morning (between 6-9am).</time_frame>
    <description>Number of patients with phosphenes</description>
  </other_outcome>
  <other_outcome>
    <measure>NT-proBNP</measure>
    <time_frame>Day of surgery post-operatively (between 6-9 pm) and morning (between 6-9 am) of post-operative days 1, 2 and 3.</time_frame>
    <description>Variance of NT-proBNP (pg/L)</description>
  </other_outcome>
  <other_outcome>
    <measure>Cardiac output (CO)</measure>
    <time_frame>Day of surgery post-operatively (between 6-9 pm) and morning (between 6-9 am) and evening (betwee 6-9pm) of post-operative days 1, 2 and 3.</time_frame>
    <description>Variance of CO measured with the ICON monitor (L/min)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">78</enrollment>
  <condition>Myocardial Injury</condition>
  <condition>Myocardial Ischemia</condition>
  <arm_group>
    <arm_group_label>Ivabradine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ivabradine will be administered in an individualized regimen adapted to the subject's heart rate at each visit in a dosage ranging from 0-7.5mg twice daily (morning and evening) from the morning of surgery until post-operative day 2, as follows:&#xD;
If heart rate is ≥101 bpm: capsule D (Ivabradine 7.5 mg);&#xD;
If heart rate is 86-100 bpm: capsule C (Ivabradine 5 mg);&#xD;
If HR is 71-85 bpm: capsule B (Ivabradine 2.5 mg);&#xD;
If HR ≤ 70 bpm or the patient received rescue treatment for bradycardia (eg.atropine) after the previous dose: capsule A (placebo).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo will be administered twice daily (morning and evening) from the morning of surgery until post-operative day 2, as follows:&#xD;
If heart rate is ≥101 bpm: capsule D (Placebo)&#xD;
If heart rate is 86-100 bpm: capsule C (Placebo)&#xD;
If HR is 71-85 bpm: capsule B (Placebo)&#xD;
If HR ≤ 70 bpm or the patient received rescue treatment for bradycardia (eg.atropine) after the previous dose: capsule A (Placebo).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivabradine</intervention_name>
    <description>Ivabradine pills will be crushed and encapsulated for adequate dosing (0, 2.5mg, 5mg or 7.5 mg) and blinding.</description>
    <arm_group_label>Ivabradine</arm_group_label>
    <other_name>Procoralan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Mannitol will be encapsulated for adequate blinding.</description>
    <arm_group_label>Ivabradine</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed Consent as documented by signature of patient; AND&#xD;
&#xD;
          -  Undergoing intermediate or high-risk non-cardiac surgery (as defined in European&#xD;
             Society of Anaesthesiology guidelines) AND;&#xD;
&#xD;
          -  One of the following:&#xD;
&#xD;
             o≥ 75 years old OR; o≥ 45 years old AND at least 1 risk factors independently&#xD;
             associated with perioperative myocardial injury (history of coronary artery disease,&#xD;
             chronic heart failure, peripheral artery disease, ischemic stroke, hypertension,&#xD;
             diabetes mellitus, chronic kidney disease).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to provide informed consent;&#xD;
&#xD;
          -  History of hypersensitivity or allergy to ivabradine;&#xD;
&#xD;
          -  Emergency surgery (to be done within 24h of diagnosis);&#xD;
&#xD;
          -  Shock or acute decompensated heart failure at trial inclusion;&#xD;
&#xD;
          -  Low cardiac output syndrome;&#xD;
&#xD;
          -  Arrhythmia:&#xD;
&#xD;
               -  Atrial fibrillation or flutter;&#xD;
&#xD;
               -  AV-block of 3rd degree;&#xD;
&#xD;
               -  Sick sinus syndrome;&#xD;
&#xD;
               -  Sino-atrial block;&#xD;
&#xD;
          -  Pacemaker dependency;&#xD;
&#xD;
          -  Unstable angina;&#xD;
&#xD;
          -  Acute myocardial infarction in the 3 months preceding the trial;&#xD;
&#xD;
          -  Stroke in the 3 months preceding the trial;&#xD;
&#xD;
          -  Cirrhosis Child B and C;&#xD;
&#xD;
          -  Renal failure with a Estimated Glomerular filtration rate ≤ 15 ml/min/1.73m2;&#xD;
&#xD;
          -  Treatment with a strong cytochrome P450 3A4 inhibitors such as azole antifungals&#xD;
             (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin;&#xD;
             josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and&#xD;
             nefazodone;&#xD;
&#xD;
          -  Treatment with verapamil or diltiazem which are moderate CYP3A4 inhibitors and PGP&#xD;
             inducers with heart rate reducing properties;&#xD;
&#xD;
          -  Women who are pregnant or breast feeding;&#xD;
&#xD;
          -  Childbearing potential (Of note, woman with history of hysterectomy, surgical&#xD;
             sterilization or menopause for longer than 2 years are not considered with&#xD;
             childbearing potential, independent of their age);&#xD;
&#xD;
          -  Participation in another study with investigational drug within the 30 days preceding&#xD;
             and during the present study;&#xD;
&#xD;
          -  Previous enrolment into the current study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bernardo Bollen Pinto, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Geneva</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Geneva University Hospitals</name>
      <address>
        <city>Geneva</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <reference>
    <citation>Puelacher C, Lurati Buse G, Seeberger D, Sazgary L, Marbot S, Lampart A, Espinola J, Kindler C, Hammerer A, Seeberger E, Strebel I, Wildi K, Twerenbold R, du Fay de Lavallaz J, Steiner L, Gurke L, Breidthardt T, Rentsch K, Buser A, Gualandro DM, Osswald S, Mueller C; BASEL-PMI Investigators. Perioperative Myocardial Injury After Noncardiac Surgery: Incidence, Mortality, and Characterization. Circulation. 2018 Mar 20;137(12):1221-1232. doi: 10.1161/CIRCULATIONAHA.117.030114. Epub 2017 Dec 4.</citation>
    <PMID>29203498</PMID>
  </reference>
  <reference>
    <citation>Duceppe E, Parlow J, MacDonald P, Lyons K, McMullen M, Srinathan S, Graham M, Tandon V, Styles K, Bessissow A, Sessler DI, Bryson G, Devereaux PJ. Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk Assessment and Management for Patients Who Undergo Noncardiac Surgery. Can J Cardiol. 2017 Jan;33(1):17-32. doi: 10.1016/j.cjca.2016.09.008. Epub 2016 Oct 4. Erratum In: Can J Cardiol. 2017 Dec;33(12 ):1735.</citation>
    <PMID>27865641</PMID>
  </reference>
  <reference>
    <citation>Chen A, Elia N, Dunaiceva J, Rudiger A, Walder B, Bollen Pinto B. Effect of ivabradine on major adverse cardiovascular events and mortality in critically ill patients: a systematic review and meta-analyses of randomised controlled trials with trial sequential analyses. Br J Anaesth. 2020 Jun;124(6):726-738. doi: 10.1016/j.bja.2020.01.027. Epub 2020 Mar 6.</citation>
    <PMID>32147100</PMID>
  </reference>
  <reference>
    <citation>Abbott TEF, Pearse RM, Archbold RA, Ahmad T, Niebrzegowska E, Wragg A, Rodseth RN, Devereaux PJ, Ackland GL. A Prospective International Multicentre Cohort Study of Intraoperative Heart Rate and Systolic Blood Pressure and Myocardial Injury After Noncardiac Surgery: Results of the VISION Study. Anesth Analg. 2018 Jun;126(6):1936-1945. doi: 10.1213/ANE.0000000000002560.</citation>
    <PMID>29077608</PMID>
  </reference>
  <reference>
    <citation>Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, Lancaster GA; PAFS consensus group. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016 Oct 24;355:i5239. doi: 10.1136/bmj.i5239.</citation>
    <PMID>27777223</PMID>
  </reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>February 25, 2022</last_update_submitted>
  <last_update_submitted_qc>February 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Geneva</investigator_affiliation>
    <investigator_full_name>Bernardo Bollen Pinto, MD PhD</investigator_full_name>
    <investigator_title>Senior Registrar and Research Fellow</investigator_title>
  </responsible_party>
  <keyword>ivabradine</keyword>
  <keyword>heart rate</keyword>
  <keyword>pilot study</keyword>
  <keyword>myocardial injury after non-cardiac surgery</keyword>
  <keyword>perioperative myocardial injury</keyword>
  <keyword>feasibility study</keyword>
  <keyword>perioperative medicine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Ischemia</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_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/NCT04436016
org study id: PROTECTIN Pilot
secondary id: SNCTP000003728
nct id: NCT04436016
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Perioperative myocardial injury (PMI) after non-cardiac surgery (NCS), i.e. the elevation of
      postoperative troponin, occurs in nearly 20% of patients older than 45 years undergoing NCS
      and is independently and strongly associated with post-operative mortality (30-day mortality
      up to 10%). With over 300 million surgical interventions every year worldwide, PMI has a high
      clinical relevance on the health of the population.

      Heart rate (HR) is an independent and modifiable risk factor for PMI and death after
      non-cardiac surgery. Numerous studies showed that beta-blockers decrease myocardial ischemia
      after surgery in a heart-rate dependent manner, but this beneficial effect is surpassed by an
      increased incidence of perioperative hypotension and death. Currently, no single intervention
      is available to decrease the risk of perioperative cardiac complications. Ivabradine (IVA) is
      a negative chronotropic agent without significant effects on contractility or vascular tone
      and has been shown to improve outcomes in the setting of chronic and acute heart diseases.

      Rationale for pilot feasibility trial: the planned definitive large trial is a multicenter
      trial to investigate the efficacy of ivabradine to decrease perioperative myocardial injury.
      The intervention planned is complex and demands important resources. The investigators
      designed this pilot study to inform on the feasibility of the definitive large trial. This
      pilot study will also provide additional information that could help investigators improve
      the definitive large trial regarding recruitment, refinements to the study protocol and
      improving the participant's experience.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Single center, randomized, placebo-controlled, double-blind, parallel group, feasibility pilot trial.
Patients will be randomized to receive ivabradine or placebo.
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Appropriate dosage rate
time frame: From the morning (6-9 am) of the day of surgery of the first study participant to the evening of the second post-operative day of the last study participant (up to 1 year from first randomization).
description: Number of correct dosages administered according to the patient's heart rate at each study visit divided by the total dosages administrated
measure: Blinding success rate
time frame: From the morning (6-9 am) of the day of surgery of the first study participant to the evening of the second post-operative day of the last study participant (up to 1 year from first randomization).
description: Number of times blinding code was broken divided by the total dosages administrated
measure: Recruitment rate
time frame: Up to one year from the date participant screening begins.
description: Total number of eligible participants approached, the number recruited and randomised divided by the number of months that the trial recruited for
measure: Participant satisfaction regarding information about the study, informed consent, recruitment procedures and study participation
time frame: Screening, morning of the day surgery pre-operatively and post-operative days 1, 2 and 3.
description: Qualitative research methods (shadowing and semi-structured interviews)
measure: Perioperative myocardial injury
time frame: Day of surgery pre-operatively (between 6-9 am) and post-operatively (between 6-9 pm or within 1h after surgery if surgery ends after 9pm) and morning (between 6-9 am) of post-operative days 1, 2, 3 and day of hospital discharge.
description: Variance of high-sensitive cardiac troponin T (ng/L)
measure: Heart rate
time frame: Day of surgery pre-operatively (between 6-9 am) and post-operatively (between 6-9 pm or within 1h after surgery if surgery ends after 9pm) and morning (between 6-9 am) of post-operative days 1, 2, 3 and day of hospital discharge.
description: Variance of resting heart rate
measure: Ivabradine dosage
time frame: Day of surgery pre-operatively (between 6-9 am) and morning (between 6-9 am) of post-operative days 1 and 2.
description: Variance
measure: Quality of Recovery
time frame: Morning (between 6-9 am) of post-operative days 1, 3 and at day of hospital discharge.
description: Variance of Quality of Recovery assessed with Quality of Recovery-15 scale (range from 0 to 150, with higher scores indicating a better outcome)
measure: Difficulty in following study protocol and administrating study drug
time frame: Morning (between 6 and 9 am) and evening (between 6 and 9 pm) of day of sugery and post-operative days 1 and 2.
description: 4-point Likert scale (Study personnel will be asked "The decision to administer the study drug according to the patient's heart rate was straightforward". Answers range from Strongly agree, Agree, Disagree to Strongly disagree)
measure: Bradycardia
time frame: From the morning of the day of surgery when the first study intervention (between 6-9am) is adminitstered until post-operative day 3 in the morning (between 6-9am).
description: Number of patients with those with a heart rate <50 or requiring an intervention to increase heart rate as atropine
measure: Atrial fibrilation
time frame: From the morning of the day of surgery when the first study intervention (between 6-9am) is adminitstered until post-operative day 3 in the morning (between 6-9am).
description: Number of patients with atrial fibrilation
measure: Phosphenes
time frame: From the morning of the day of surgery when the first study intervention (between 6-9am) is adminitstered until post-operative day 3 in the morning (between 6-9am).
description: Number of patients with phosphenes
measure: NT-proBNP
time frame: Day of surgery post-operatively (between 6-9 pm) and morning (between 6-9 am) of post-operative days 1, 2 and 3.
description: Variance of NT-proBNP (pg/L)
measure: Cardiac output (CO)
time frame: Day of surgery post-operatively (between 6-9 pm) and morning (between 6-9 am) and evening (betwee 6-9pm) of post-operative days 1, 2 and 3.
description: Variance of CO measured with the ICON monitor (L/min)
arm group label: Ivabradine
arm group type: Experimental
description: Ivabradine will be administered in an individualized regimen adapted to the subject's heart rate at each visit in a dosage ranging from 0-7.5mg twice daily (morning and evening) from the morning of surgery until post-operative day 2, as follows:
If heart rate is ≥101 bpm: capsule D (Ivabradine 7.5 mg);
If heart rate is 86-100 bpm: capsule C (Ivabradine 5 mg);
If HR is 71-85 bpm: capsule B (Ivabradine 2.5 mg);
If HR ≤ 70 bpm or the patient received rescue treatment for bradycardia (eg.atropine) after the previous dose: capsule A (placebo).
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo will be administered twice daily (morning and evening) from the morning of surgery until post-operative day 2, as follows:
If heart rate is ≥101 bpm: capsule D (Placebo)
If heart rate is 86-100 bpm: capsule C (Placebo)
If HR is 71-85 bpm: capsule B (Placebo)
If HR ≤ 70 bpm or the patient received rescue treatment for bradycardia (eg.atropine) after the previous dose: capsule A (Placebo).
intervention type: Drug
intervention name: Ivabradine
description: Ivabradine pills will be crushed and encapsulated for adequate dosing (0, 2.5mg, 5mg or 7.5 mg) and blinding.
arm group label: Ivabradine
other name: Procoralan
intervention type: Drug
intervention name: Placebo
description: Mannitol will be encapsulated for adequate blinding.
arm group label: Ivabradine
arm group label: Placebo
criteria: 
gender: All
minimum age: 45 Years
maximum age: N/A
healthy volunteers: No
last name: Bernardo Bollen Pinto, MD PhD
role: Principal Investigator
affiliation: University Hospital, Geneva
facility: 
country: Switzerland
citation: Puelacher C, Lurati Buse G, Seeberger D, Sazgary L, Marbot S, Lampart A, Espinola J, Kindler C, Hammerer A, Seeberger E, Strebel I, Wildi K, Twerenbold R, du Fay de Lavallaz J, Steiner L, Gurke L, Breidthardt T, Rentsch K, Buser A, Gualandro DM, Osswald S, Mueller C; BASEL-PMI Investigators. Perioperative Myocardial Injury After Noncardiac Surgery: Incidence, Mortality, and Characterization. Circulation. 2018 Mar 20;137(12):1221-1232. doi: 10.1161/CIRCULATIONAHA.117.030114. Epub 2017 Dec 4.
PMID: 29203498
citation: Duceppe E, Parlow J, MacDonald P, Lyons K, McMullen M, Srinathan S, Graham M, Tandon V, Styles K, Bessissow A, Sessler DI, Bryson G, Devereaux PJ. Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk Assessment and Management for Patients Who Undergo Noncardiac Surgery. Can J Cardiol. 2017 Jan;33(1):17-32. doi: 10.1016/j.cjca.2016.09.008. Epub 2016 Oct 4. Erratum In: Can J Cardiol. 2017 Dec;33(12 ):1735.
PMID: 27865641
citation: Chen A, Elia N, Dunaiceva J, Rudiger A, Walder B, Bollen Pinto B. Effect of ivabradine on major adverse cardiovascular events and mortality in critically ill patients: a systematic review and meta-analyses of randomised controlled trials with trial sequential analyses. Br J Anaesth. 2020 Jun;124(6):726-738. doi: 10.1016/j.bja.2020.01.027. Epub 2020 Mar 6.
PMID: 32147100
citation: Abbott TEF, Pearse RM, Archbold RA, Ahmad T, Niebrzegowska E, Wragg A, Rodseth RN, Devereaux PJ, Ackland GL. A Prospective International Multicentre Cohort Study of Intraoperative Heart Rate and Systolic Blood Pressure and Myocardial Injury After Noncardiac Surgery: Results of the VISION Study. Anesth Analg. 2018 Jun;126(6):1936-1945. doi: 10.1213/ANE.0000000000002560.
PMID: 29077608
citation: Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, Lancaster GA; PAFS consensus group. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016 Oct 24;355:i5239. doi: 10.1136/bmj.i5239.
PMID: 27777223
responsible party type: Principal Investigator
investigator affiliation: University Hospital, Geneva
investigator full name: Bernardo Bollen Pinto, MD PhD
investigator title: Senior Registrar and Research Fellow
mesh term: Myocardial Ischemia
mesh term: Ischemia
mesh term: Wounds and Injuries
sharing ipd: No