<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/NCT03778554</url>
  </required_header>
  <id_info>
    <org_study_id>2018-002699-42</org_study_id>
    <secondary_id>2018-002699-42</secondary_id>
    <nct_id>NCT03778554</nct_id>
  </id_info>
  <brief_title>Danish Trial of Beta Blocker Treatment After Myocardial Infarction Without Reduced Ejection Fraction</brief_title>
  <acronym>DANBLOCK</acronym>
  <official_title>Danish Trial of Beta Blocker Treatment After Myocardial Infarction Without Reduced Ejection Fraction (DANBLOCK)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bispebjerg Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amager Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bispebjerg Frederiksberg Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bornholm Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Gentofte Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Glostrup University Hospital, Copenhagen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Herlev Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hvidovre University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nordsjaelland Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Holbaek Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nykoebing Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Naestved Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nordsjaellands Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zealand University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Slagelse Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Odense University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Svendborg Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sydvestjysk Sygehus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital of Southern Jutland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sygehus Lillebaelt (Vejle and Kolding)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aarhus Universitetshospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospitalsenheden Midt</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospitalsenheden Vest</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Regionshospitalet Horsens</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Silkeborg Sygehus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aalborg University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Bispebjerg 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine whether long-term treatment with oral betablocker therapy after myocardial&#xD;
      infarction in patient with no heart failure reduces the composite outcome of recurrent&#xD;
      non-fatal MI, all-cause mortality, revascularisation with percutaneous coronary intervention&#xD;
      or coronary artery bypass graft, stroke, ventricular arrhythmia, cardiac arrest with&#xD;
      successful resuscitation or heart failure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aim: To determine whether long-term treatment with oral betablocker (BB) therapy after&#xD;
      myocardial infarction (MI) in patient with no heart failure reduces the composite outcome of&#xD;
      recurrent non-fatal MI, all-cause mortality, revascularisation with percutaneous coronary&#xD;
      intervention or coronary artery bypass graft, stroke, ventricular arrhythmia, cardiac arrest&#xD;
      with successful resuscitation due to cardiac cause or heart failure.&#xD;
&#xD;
      Intervention: BB therapy versus no therapy.&#xD;
&#xD;
      Main Inclusion Criteria: Patient that have suffered a MI, both Non-ST elevation MI and ST&#xD;
      elevation MI and can be randomized within 14 days of MI with no signs of heart failure and a&#xD;
      left ventricular ejection fraction&gt;40%.&#xD;
&#xD;
      Main Exclusion Criteria: Any indication or contraindication for BB treatment other than&#xD;
      secondary prevention according to the treating cardiologist&#xD;
&#xD;
      Primary study endpoint: The composite of all-cause mortality, recurrent non-fatal MI,&#xD;
      revascularisation with PCI or CABG, stroke, ventricular arrhythmia, cardiac arrest with&#xD;
      successful resuscitation due to cardiac cause or heart failure.&#xD;
&#xD;
      Sample Size: A total of approximately 3570 patients will be recruited and randomized 1:1 to&#xD;
      BB treatment (type and dosage according to treating physician) or no BB treatment. Treatment&#xD;
      must be initiated within 14 days of MI.&#xD;
&#xD;
      Location: All departments of cardiology in Denmark are invited to participate. All patients&#xD;
      admitted to hospital for MI will be screened for in- and exclusion criteria and contacted if&#xD;
      eligible.&#xD;
&#xD;
      Treatment Duration: Estimated (non) treatment duration of 6 months-6 years.&#xD;
&#xD;
      Follow-up: Patients will be followed from the randomization date until end of follow-up with&#xD;
      respect to the primary and most secondary endpoints.&#xD;
&#xD;
      Assessment of primary study and safety end points: Serious adverse events (SAE) will be&#xD;
      monitored through patient reported hospital admission by surveys every 3 months combined with&#xD;
      local follow-up on patients that do not respond to surveys&#xD;
&#xD;
      Intervention and dosage of BB treatment: The intervention will be active treatment with BB,&#xD;
      type and dosage according to treating cardiologist choice and control will be standard care&#xD;
      (without BB treatment). The treating cardiologist is recommended to use the highest dose&#xD;
      deemed tolerable for the patient at the time of randomization. Dosage, adherence and&#xD;
      cross-over will be monitored through linkage to the Danish Register of Medical Product&#xD;
      Statistics.&#xD;
&#xD;
      Sample size considerations: Assuming a hazard ratio of 1.2 for the non-treated group compared&#xD;
      to the treated the DANBLOCK trial has 80% power to detect this effect with an accumulation of&#xD;
      900 events of the primary endpoint. With approximately 3570 patients randomized the&#xD;
      investigators expect to reach 900 events within the study period.&#xD;
&#xD;
      Statistical Analysis: Intention-to-treat analysis will be carried out. Additionally, a&#xD;
      secondary per-protocol analysis will be performed, where compliant BB-users patients are&#xD;
      considered exposed during follow-up. Outcome analysis will be assessed by using cumulative&#xD;
      incidence and Cox-regressions.&#xD;
&#xD;
      Data Safety Monitoring Board (DSMB): This committee consisting of two senior cardiologists&#xD;
      and one trial-science statistician will overview safety and will have access to unblinded&#xD;
      data. They will formally review the accumulating data every 6 months throughout the study&#xD;
      period to ensure there is no avoidable increased harm to patients. The DSMB may recommend&#xD;
      trial termination due to excess risk associated with no treatment with BB.&#xD;
&#xD;
      Recruitment: All patients admitted to hospital for MI will be screened for in- and exclusion&#xD;
      criteria and contacted if eligible. Logistics of identifying and contacting the patients will&#xD;
      be organized locally; some hospitals will randomize patients before discharge, others will&#xD;
      contact patients after discharge. Patients will be randomized 1:1.&#xD;
&#xD;
      Publication policy: On study completion the results will be submitted for publication in an&#xD;
      international medical journal. The results of this study will also be submitted to the&#xD;
      Competent Authority and the Ethics Committee according to EU and Danish regulations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 17, 2018</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Prospective, randomized, controlled, open-label, blinded endpoint (PROBE design)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The composite endpoint of all-cause mortality, recurrent non-fatal MI, revascularisation with PCI or CABG, stroke, ventricular arrhythmia, cardiac arrest with successful resuscitation due to cardiac cause or heart failure.</measure>
    <time_frame>Estimated maximal follow-up 6 months-6 years</time_frame>
    <description>Time to the composite of all-cause mortality, recurrent non-fatal MI, revascularisation with PCI or CABG, stroke, ventricular arrhythmia, cardiac arrest with successful resuscitation due to cardiac cause or heart failure on an intention to treat analysis. The composite outcome will be assessed through nationwide registries.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The incidence of cardiovascular mortality</measure>
    <time_frame>Estimated maximal follow-up 6 months - 6 years</time_frame>
    <description>Time to cardiovascular mortality assessed through nationwide registries.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of atrial fibrillation/atrial flutter</measure>
    <time_frame>Estimated maximal follow-up 6 months - 6 years</time_frame>
    <description>Time to hospital admission of the outcome assessed through nationwide registries.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of cardiac arrest</measure>
    <time_frame>Estimated maximal follow-up 6 months - 6 years</time_frame>
    <description>Time to cardiac arrest assessed through nationwide registries.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of ventricular arrhythmias</measure>
    <time_frame>Estimated maximal follow-up 6 months - 6 years</time_frame>
    <description>Time to hospital admission of the outcome assessed through nationwide registries.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Angina symptoms</measure>
    <time_frame>Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months</time_frame>
    <description>Canadian Cardiovascular Society (CCS) grading of angina pectoris.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exercise capacity</measure>
    <time_frame>After 24 months and at study end.</time_frame>
    <description>Data on exercise capacity (VO2peak) will measured before and after rehabilitation and recorded in the Danish Cardiac Rehabilitation database after 24 months and at study end. This data is only available for patients participating in cardiac rehabilitation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of bradycardia, syncope or need for pacemaker</measure>
    <time_frame>Estimated maximal follow-up 6 months - 6 years</time_frame>
    <description>Time to hospital admission of the outcome assessed through nationwide registries.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of asthma and chronic obstructive pulmonary disease symptoms</measure>
    <time_frame>Estimated maximal follow-up 6 months - 6 years</time_frame>
    <description>Time to hospital admission of the outcome assessed through nationwide registries.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure control</measure>
    <time_frame>After 24 months and at study end.</time_frame>
    <description>Data on blood pressure (systolic and diastolic ) will measured before and after rehabilitation and recorded in the Danish Cardiac Rehabilitation database after 24 months and at study end. This data is only available for patients participating in cardiac rehabilitation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diabetes (new diagnosis and dysregulation)</measure>
    <time_frame>After 24 months and at study end.</time_frame>
    <description>Data on diabetes (new diagnosis and dysregulation) will measured through hba1c before and after rehabilitation and recorded in the Danish Cardiac Rehabilitation database after 24 months and at study end. This data is only available for patients participating in cardiac rehabilitation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of peripheral artery disease</measure>
    <time_frame>Estimated maximal follow-up 6 months - 6 years</time_frame>
    <description>Time to hospital admission of the outcome assessed through nationwide registries.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of heart failure</measure>
    <time_frame>Estimated maximal follow-up 6 months - 6 years</time_frame>
    <description>Time to hospital admission of the outcome assessed through nationwide registries.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of mortality</measure>
    <time_frame>Estimated maximal follow-up 6 months - 6 years</time_frame>
    <description>Time to all-cause mortality assessed through nationwide registries.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of myocardial infarction</measure>
    <time_frame>Estimated maximal follow-up 6 months - 6 years</time_frame>
    <description>Time to hospital admission of the outcome assessed through nationwide registries.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of unstable angina pectoris</measure>
    <time_frame>Estimated maximal follow-up 6 months - 6 years</time_frame>
    <description>Time to hospital admission of the outcome assessed through nationwide registries.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of stroke</measure>
    <time_frame>Estimated maximal follow-up 6 months - 6 years</time_frame>
    <description>Time to hospital admission of the outcome assessed through nationwide registries.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life measure</measure>
    <time_frame>Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months</time_frame>
    <description>EQ5D (a measure of health-related quality of life that can be used in a wide range of health conditions and treatments)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measures of depression and anxiety</measure>
    <time_frame>Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months</time_frame>
    <description>HADS (Hospital Anxiety and Depression Scale)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measures of sexual dysfunction</measure>
    <time_frame>Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months</time_frame>
    <description>The International Index of Erectile Function (IIEF) and Female Sexual Function Index (FSFI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measures of sleeping disorder</measure>
    <time_frame>Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months</time_frame>
    <description>Bergen insomnia Scale</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">3570</enrollment>
  <condition>Acute Myocardial Infarction</condition>
  <condition>Non-ST Elevation Myocardial Infarction (nSTEMI)</condition>
  <condition>ST Elevation Myocardial Infarction</condition>
  <arm_group>
    <arm_group_label>Beta blocker treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment with beta blockers plus standard of care. Type and dosage according to treating cardiologist choice&#xD;
Bisoprolol up to a total dose of 10 mg daily&#xD;
Carvedilol up to a total dose of 50 mg daily&#xD;
Metoprolol succinate up to a total dose of 200 mg daily&#xD;
Nebivolol up to a total dose of 10 mg daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No beta blocker treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard care without beta blocker treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metoprolol Succinate</intervention_name>
    <description>Eligible patients randomized to receive long-term therapy with oral beta-blockade</description>
    <arm_group_label>Beta blocker treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bisoprolol</intervention_name>
    <description>Eligible patients randomized to receive long-term therapy with oral beta-blockade</description>
    <arm_group_label>Beta blocker treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carvedilol</intervention_name>
    <description>Eligible patients randomized to receive long-term therapy with oral beta-blockade</description>
    <arm_group_label>Beta blocker treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nebivolol</intervention_name>
    <description>Eligible patients randomized to receive long-term therapy with oral beta-blockade</description>
    <arm_group_label>Beta blocker treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Left ventricular ejection fraction &gt; 40%&#xD;
&#xD;
          -  Myocardial infarction (MI) within previous two weeks&#xD;
&#xD;
        The diagnosis of acute MI must meet the Universal European Society of Cardiology (ESC)&#xD;
        definition of MI&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinical evidence of heart failure at the time of discharge&#xD;
&#xD;
          -  Pregnancy or of child bearing age not using safe anticonception throughout the study&#xD;
             period&#xD;
&#xD;
          -  Lack of signed informed consent and expected cooperation during follow-up&#xD;
&#xD;
          -  Any medical condition where beta blocker treatment is indicated according to the&#xD;
             treating physician&#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>Eva IB Prescott, MD, DMsC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Bispebjerg Frederiksberg University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Thomas SG Sehested, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Bispebjerg Frederiksberg Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Thomas SG Sehested, MD</last_name>
    <phone>20836010</phone>
    <phone_ext>+45</phone_ext>
    <email>tsg.sehested@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Anna MD Kristensen, MD</last_name>
    <phone>+4524413242</phone>
    <email>anna.meta.dyrvig.kristensen.02@regionh.dk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Bispebjerg Hospital, Dept. of Cardiology Y builing 67, 1.floor, Bispebjerg Bakke 23</name>
      <address>
        <city>Copenhagen</city>
        <zip>2400</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eva Prescott, MD, DMSc</last_name>
      <phone>+45 4026 2134</phone>
      <email>Eva.Irene.Bossano.Prescott@regionh.dk</email>
    </contact>
    <contact_backup>
      <last_name>Camilla Kjaergaard</last_name>
      <phone>+45 23311197</phone>
      <email>camilla.lyngby.kjaergaard@regionh.dk</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 16, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>December 12, 2022</last_update_submitted>
  <last_update_submitted_qc>December 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Bispebjerg Hospital</investigator_affiliation>
    <investigator_full_name>Eva Prescott</investigator_full_name>
    <investigator_title>Professor, MD, PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>ST Elevation Myocardial Infarction</mesh_term>
    <mesh_term>Non-ST Elevated Myocardial Infarction</mesh_term>
    <mesh_term>Infarction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metoprolol</mesh_term>
    <mesh_term>Carvedilol</mesh_term>
    <mesh_term>Nebivolol</mesh_term>
    <mesh_term>Bisoprolol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03778554
org study id: 2018-002699-42
secondary id: 2018-002699-42
nct id: NCT03778554
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To determine whether long-term treatment with oral betablocker therapy after myocardial
      infarction in patient with no heart failure reduces the composite outcome of recurrent
      non-fatal MI, all-cause mortality, revascularisation with percutaneous coronary intervention
      or coronary artery bypass graft, stroke, ventricular arrhythmia, cardiac arrest with
      successful resuscitation or heart failure.
Aim: To determine whether long-term treatment with oral betablocker (BB) therapy after
      myocardial infarction (MI) in patient with no heart failure reduces the composite outcome of
      recurrent non-fatal MI, all-cause mortality, revascularisation with percutaneous coronary
      intervention or coronary artery bypass graft, stroke, ventricular arrhythmia, cardiac arrest
      with successful resuscitation due to cardiac cause or heart failure.

      Intervention: BB therapy versus no therapy.

      Main Inclusion Criteria: Patient that have suffered a MI, both Non-ST elevation MI and ST
      elevation MI and can be randomized within 14 days of MI with no signs of heart failure and a
      left ventricular ejection fraction>40%.

      Main Exclusion Criteria: Any indication or contraindication for BB treatment other than
      secondary prevention according to the treating cardiologist

      Primary study endpoint: The composite of all-cause mortality, recurrent non-fatal MI,
      revascularisation with PCI or CABG, stroke, ventricular arrhythmia, cardiac arrest with
      successful resuscitation due to cardiac cause or heart failure.

      Sample Size: A total of approximately 3570 patients will be recruited and randomized 1:1 to
      BB treatment (type and dosage according to treating physician) or no BB treatment. Treatment
      must be initiated within 14 days of MI.

      Location: All departments of cardiology in Denmark are invited to participate. All patients
      admitted to hospital for MI will be screened for in- and exclusion criteria and contacted if
      eligible.

      Treatment Duration: Estimated (non) treatment duration of 6 months-6 years.

      Follow-up: Patients will be followed from the randomization date until end of follow-up with
      respect to the primary and most secondary endpoints.

      Assessment of primary study and safety end points: Serious adverse events (SAE) will be
      monitored through patient reported hospital admission by surveys every 3 months combined with
      local follow-up on patients that do not respond to surveys

      Intervention and dosage of BB treatment: The intervention will be active treatment with BB,
      type and dosage according to treating cardiologist choice and control will be standard care
      (without BB treatment). The treating cardiologist is recommended to use the highest dose
      deemed tolerable for the patient at the time of randomization. Dosage, adherence and
      cross-over will be monitored through linkage to the Danish Register of Medical Product
      Statistics.

      Sample size considerations: Assuming a hazard ratio of 1.2 for the non-treated group compared
      to the treated the DANBLOCK trial has 80% power to detect this effect with an accumulation of
      900 events of the primary endpoint. With approximately 3570 patients randomized the
      investigators expect to reach 900 events within the study period.

      Statistical Analysis: Intention-to-treat analysis will be carried out. Additionally, a
      secondary per-protocol analysis will be performed, where compliant BB-users patients are
      considered exposed during follow-up. Outcome analysis will be assessed by using cumulative
      incidence and Cox-regressions.

      Data Safety Monitoring Board (DSMB): This committee consisting of two senior cardiologists
      and one trial-science statistician will overview safety and will have access to unblinded
      data. They will formally review the accumulating data every 6 months throughout the study
      period to ensure there is no avoidable increased harm to patients. The DSMB may recommend
      trial termination due to excess risk associated with no treatment with BB.

      Recruitment: All patients admitted to hospital for MI will be screened for in- and exclusion
      criteria and contacted if eligible. Logistics of identifying and contacting the patients will
      be organized locally; some hospitals will randomize patients before discharge, others will
      contact patients after discharge. Patients will be randomized 1:1.

      Publication policy: On study completion the results will be submitted for publication in an
      international medical journal. The results of this study will also be submitted to the
      Competent Authority and the Ethics Committee according to EU and Danish regulations.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective, randomized, controlled, open-label, blinded endpoint (PROBE design)
primary purpose: Treatment
masking: None (Open Label)
measure: The composite endpoint of all-cause mortality, recurrent non-fatal MI, revascularisation with PCI or CABG, stroke, ventricular arrhythmia, cardiac arrest with successful resuscitation due to cardiac cause or heart failure.
time frame: Estimated maximal follow-up 6 months-6 years
description: Time to the composite of all-cause mortality, recurrent non-fatal MI, revascularisation with PCI or CABG, stroke, ventricular arrhythmia, cardiac arrest with successful resuscitation due to cardiac cause or heart failure on an intention to treat analysis. The composite outcome will be assessed through nationwide registries.
measure: The incidence of cardiovascular mortality
time frame: Estimated maximal follow-up 6 months - 6 years
description: Time to cardiovascular mortality assessed through nationwide registries.
measure: The incidence of atrial fibrillation/atrial flutter
time frame: Estimated maximal follow-up 6 months - 6 years
description: Time to hospital admission of the outcome assessed through nationwide registries.
measure: The incidence of cardiac arrest
time frame: Estimated maximal follow-up 6 months - 6 years
description: Time to cardiac arrest assessed through nationwide registries.
measure: The incidence of ventricular arrhythmias
time frame: Estimated maximal follow-up 6 months - 6 years
description: Time to hospital admission of the outcome assessed through nationwide registries.
measure: Angina symptoms
time frame: Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months
description: Canadian Cardiovascular Society (CCS) grading of angina pectoris.
measure: Exercise capacity
time frame: After 24 months and at study end.
description: Data on exercise capacity (VO2peak) will measured before and after rehabilitation and recorded in the Danish Cardiac Rehabilitation database after 24 months and at study end. This data is only available for patients participating in cardiac rehabilitation.
measure: The incidence of bradycardia, syncope or need for pacemaker
time frame: Estimated maximal follow-up 6 months - 6 years
description: Time to hospital admission of the outcome assessed through nationwide registries.
measure: The incidence of asthma and chronic obstructive pulmonary disease symptoms
time frame: Estimated maximal follow-up 6 months - 6 years
description: Time to hospital admission of the outcome assessed through nationwide registries.
measure: Blood pressure control
time frame: After 24 months and at study end.
description: Data on blood pressure (systolic and diastolic ) will measured before and after rehabilitation and recorded in the Danish Cardiac Rehabilitation database after 24 months and at study end. This data is only available for patients participating in cardiac rehabilitation.
measure: Diabetes (new diagnosis and dysregulation)
time frame: After 24 months and at study end.
description: Data on diabetes (new diagnosis and dysregulation) will measured through hba1c before and after rehabilitation and recorded in the Danish Cardiac Rehabilitation database after 24 months and at study end. This data is only available for patients participating in cardiac rehabilitation.
measure: The incidence of peripheral artery disease
time frame: Estimated maximal follow-up 6 months - 6 years
description: Time to hospital admission of the outcome assessed through nationwide registries.
measure: The incidence of heart failure
time frame: Estimated maximal follow-up 6 months - 6 years
description: Time to hospital admission of the outcome assessed through nationwide registries.
measure: The incidence of mortality
time frame: Estimated maximal follow-up 6 months - 6 years
description: Time to all-cause mortality assessed through nationwide registries.
measure: The incidence of myocardial infarction
time frame: Estimated maximal follow-up 6 months - 6 years
description: Time to hospital admission of the outcome assessed through nationwide registries.
measure: The incidence of unstable angina pectoris
time frame: Estimated maximal follow-up 6 months - 6 years
description: Time to hospital admission of the outcome assessed through nationwide registries.
measure: The incidence of stroke
time frame: Estimated maximal follow-up 6 months - 6 years
description: Time to hospital admission of the outcome assessed through nationwide registries.
measure: Quality of life measure
time frame: Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months
description: EQ5D (a measure of health-related quality of life that can be used in a wide range of health conditions and treatments)
measure: Measures of depression and anxiety
time frame: Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months
description: HADS (Hospital Anxiety and Depression Scale)
measure: Measures of sexual dysfunction
time frame: Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months
description: The International Index of Erectile Function (IIEF) and Female Sexual Function Index (FSFI)
measure: Measures of sleeping disorder
time frame: Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months
description: Bergen insomnia Scale
arm group label: Beta blocker treatment
arm group type: Experimental
description: Treatment with beta blockers plus standard of care. Type and dosage according to treating cardiologist choice
Bisoprolol up to a total dose of 10 mg daily
Carvedilol up to a total dose of 50 mg daily
Metoprolol succinate up to a total dose of 200 mg daily
Nebivolol up to a total dose of 10 mg daily
arm group label: No beta blocker treatment
arm group type: No Intervention
description: Standard care without beta blocker treatment
intervention type: Drug
intervention name: Metoprolol Succinate
description: Eligible patients randomized to receive long-term therapy with oral beta-blockade
arm group label: Beta blocker treatment
intervention type: Drug
intervention name: Bisoprolol
description: Eligible patients randomized to receive long-term therapy with oral beta-blockade
arm group label: Beta blocker treatment
intervention type: Drug
intervention name: Carvedilol
description: Eligible patients randomized to receive long-term therapy with oral beta-blockade
arm group label: Beta blocker treatment
intervention type: Drug
intervention name: Nebivolol
description: Eligible patients randomized to receive long-term therapy with oral beta-blockade
arm group label: Beta blocker treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Eva IB Prescott, MD, DMsC
role: Principal Investigator
affiliation: Bispebjerg Frederiksberg University Hospital
last name: Thomas SG Sehested, MD
role: Study Chair
affiliation: Bispebjerg Frederiksberg Hospital
last name: Thomas SG Sehested, MD
phone: 20836010
phone ext: +45
email: tsg.sehested@gmail.com
last name: Anna MD Kristensen, MD
phone: +4524413242
email: anna.meta.dyrvig.kristensen.02@regionh.dk
facility: 
status: Recruiting
contact: 
contact backup: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Bispebjerg Hospital
investigator full name: Eva Prescott
investigator title: Professor, MD, PhD
mesh term: Myocardial Infarction
mesh term: ST Elevation Myocardial Infarction
mesh term: Non-ST Elevated Myocardial Infarction
mesh term: Infarction
mesh term: Metoprolol
mesh term: Carvedilol
mesh term: Nebivolol
mesh term: Bisoprolol
sharing ipd: Undecided