<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/NCT03278509</url>
  </required_header>
  <id_info>
    <org_study_id>EudraCT number 2017-002336-17</org_study_id>
    <nct_id>NCT03278509</nct_id>
  </id_info>
  <brief_title>Evaluation of Decreased Usage of Betablockers After Myocardial Infarction in the SWEDEHEART Registry (REDUCE-SWEDEHEART)</brief_title>
  <official_title>Randomized Evaluation of Decreased Usage of betablocCkErs After Myocardial Infarction in the SWEDEHEART Registry - A Registry-based, Randomized, Parallel, Open-label, Multicenter Trial (REDUCE-SWEDEHEART)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska Institutet</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Uppsala University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Swedish Research Council</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Karolinska Institutet</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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Long-term beta-blocker therapy has not been investigated in contemporary randomized clinical&#xD;
      trials in patients with myocardial infarction and normal heart function. The aim of this&#xD;
      study is to determine whether long-term treatment with oral beta-blockade in patients with&#xD;
      myocardial infarction and preserved left ventricular systolic ejection fraction reduces the&#xD;
      composite of death of any cause or new myocardial infarction..&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      REDUCE-SWEDEHEART is designed as a registry-based, randomized, parallel, open-label,&#xD;
      multicenter trial.&#xD;
&#xD;
      Patients, day 1-7 after myocardial infarction, who have undergone a coronary angiography and&#xD;
      with preserved left ventricular systolic ejection fraction will be randomized to either oral&#xD;
      beta-blockade (see &quot;Intervention&quot; for detailed description) at a dose according to the&#xD;
      treating physician, or no beta-blockade. To allow quick inclusion the randomization module&#xD;
      will be accessible by a simple web-based log-in procedure. Concomitantly, all baseline data&#xD;
      about each individual patient will be collected from the SWEDEHEART registry. Patients will&#xD;
      then be followed regarding all-cause mortality, myocardial infarction, heart failure, atrial&#xD;
      fibrillation, and patient-related outcome measures (for a subgroup of patients). Patients&#xD;
      that are eligible but not included in REDUCE-SWEDEHEART will also be followed regarding&#xD;
      chosen treatment and the primary and secondary endpoints.&#xD;
&#xD;
      Follow-up will continue until 379 primary endpoints have been observed (endpoint driven). All&#xD;
      analyses will be performed on the intention-to-treat set, defined as all intentionally&#xD;
      randomized patients, by randomized treatment. The primary endpoint is death or new MI.&#xD;
      Information about death will be obtained from the Swedish population registry. Information&#xD;
      regarding new myocardial infarction during hospitalization and readmission because of&#xD;
      myocardial infarction or other outcome (secondary outcomes, see section below), will be&#xD;
      obtained from the SWEDEHEART-registry (for myocardial infarction) and the patient registry of&#xD;
      the National board of health and welfare.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 11, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2025</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>A registry-based, randomized, parallel, open-label, multicenter trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to the composite of death of any cause or MI</measure>
    <time_frame>through study completion, an average of 3 year</time_frame>
    <description>Time to the composite of death of any cause or MI on an intention to treat basis (ITT)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>All-cause death</measure>
    <time_frame>through study completion, an average of 3 year</time_frame>
    <description>Time to the individual component of the primary endpoint of any cause of death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myocardial infarction</measure>
    <time_frame>through study completion, an average of 3 year</time_frame>
    <description>Time to the individual component of the primary endpoint of MI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular death</measure>
    <time_frame>through study completion, an average of 3 year</time_frame>
    <description>Time to cardiovascular death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart failure</measure>
    <time_frame>through study completion, an average of 3 year</time_frame>
    <description>Time to hospital readmission due to heart failure (primary [main] diagnosis)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Atrial fibrillation</measure>
    <time_frame>through study completion, an average of 3 year</time_frame>
    <description>Time to hospital readmission due to atrial fibrillation (primary [main] diagnosis)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bradycardia, Advanced AV-block, hypotension, syncope or need for pacemaker</measure>
    <time_frame>through study completion, an average of 3 year</time_frame>
    <description>Time to hospital readmission due to bradycardia or advanced AV-block or hypotension or syncope or need for pacemaker (primary [main] diagnosis)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Asthma or Chronic Obstructive Pulmonary Disease</measure>
    <time_frame>through study completion, an average of 3 year</time_frame>
    <description>Time to hospital readmission due to asthma or chronic obstructive pulmonary disease (primary [main] diagnosis)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stroke</measure>
    <time_frame>through study completion, an average of 3 year</time_frame>
    <description>Time to hospital readmission due to stroke (primary [main] diagnosis)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health related quality of life (HRQOL)</measure>
    <time_frame>Estimated maximal follow-up for each patient for this outcome is 1 year.</time_frame>
    <description>Health related quality of life (HRQOL) measured by EQ-5D in patients younger than 75 years of age</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health care costs</measure>
    <time_frame>through study completion, an average of 3 year</time_frame>
    <description>Health care cost analysis concerning the use beta-blocker treatment</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Anxiety and depression</measure>
    <time_frame>8 weeks and 12 months after randomization</time_frame>
    <description>Anxiety and depression measured by Hospital Anxiety and Depression Scale (HADS)</description>
  </other_outcome>
  <other_outcome>
    <measure>Wellbeing</measure>
    <time_frame>8 weeks and 12 months after randomization</time_frame>
    <description>Wellbeing measured by WHO-5 Wellbeing Index</description>
  </other_outcome>
  <other_outcome>
    <measure>Cardiac Anxiety</measure>
    <time_frame>8 weeks and 12 months after randomization</time_frame>
    <description>Cardiac Anxiety measured by Cardiac Anxiety Questionnaire (CAQ)</description>
  </other_outcome>
  <other_outcome>
    <measure>Sexual function</measure>
    <time_frame>8 weeks and 12 months after randomization</time_frame>
    <description>Sexual function measured by Arizona Sexual Experiences Scale (ASEX)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">5000</enrollment>
  <condition>Acute Myocardial Infarction</condition>
  <condition>Non-ST Elevation Myocardial Infarction</condition>
  <condition>ST Elevation Myocardial Infarction</condition>
  <arm_group>
    <arm_group_label>Oral beta-blocker treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to beta-blockade will be prescribed oral beta-blocker (metoprolol succinate or bisoprolol) at a dose according to the treating physician. Metoprolol succinate will be strongly recommended as first choice. Bisoprolol will be allowed as an alternative. Atenolol (or any other beta-blocker therapy) will not be allowed. The treating physician will be encouraged to aim for a dose of ≥ 100 mg for metoprolol succinate and ≥ 5 mg for bisoprolol. Prescribed treatment and dosing will be registered. Initiation (whether the prescribed drug is dispensed) and adherence (defined as proportion of prescribed tablets that are dispensed), and persistence (time on treatment) will also be recorded via the Drug prescription registry.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No beta-blocker treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients randomized to no beta-blockade will be discouraged to use beta-blockade as long as there is no other indication than strictly secondary prevention after myocardial infarction. Patients assigned to no beta-blockade also receive best evidence-based care, without beta-blockers. For blood pressure control, other drugs than beta-blockers will be recommended as first-line treatment. Regarding later use of beta-blockade, follow up is performed in the Drug prescription registry. Patients will be asked to provide future physicians with the written information about the study when beta-blockade treatment is discussed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metoprolol Succinate</intervention_name>
    <description>Eligible patients randomized to active treatment will receive long-term oral beta-blockade (metoprolol succinate or bisoprolol).</description>
    <arm_group_label>Oral beta-blocker treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bisoprolol</intervention_name>
    <description>Please see the section above.</description>
    <arm_group_label>Oral beta-blocker treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age≥18 years.&#xD;
&#xD;
          2. Day 1-7 after MI as defined by the universal definition of MI, type 1, included in the&#xD;
             SWEDEHEART registry.&#xD;
&#xD;
          3. Undergone coronary angiography during hospitalization.&#xD;
&#xD;
          4. Obstructive coronary artery disease documented by coronary angiography, i.e. stenosis&#xD;
             ≥ 50 %, FFR ≤ 0.80 or iFR ≤ 0.89 in any segment at any time point before&#xD;
             randomization.&#xD;
&#xD;
          5. Echocardiography performed after the MI showing a normal ejection fraction (EF≥50%).&#xD;
&#xD;
          6. Written informed consent obtained.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any condition that may influence the patient's ability to comply with study protocol.&#xD;
&#xD;
          2. Contraindications for beta-blockade&#xD;
&#xD;
          3. Indication for beta-blockade other than as secondary prevention 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>Tomas Jernberg, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska Institutet</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bertil Lindahl, MD PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Uppsala, Clinical Sciences</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Susanne Heller</last_name>
    <phone>+46 18 611 95 00</phone>
    <email>susanne.heller@ucr.uu.se</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Troels Yndigegn, MD</last_name>
    <phone>0046732020045</phone>
    <email>troels.yndigegn@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Danderyd Hospital, Cardiac Intensive Care</name>
      <address>
        <city>Danderyd</city>
        <state>Stockholms Län</state>
        <zip>182 88</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tomas Jernberg, MD, PhD</last_name>
      <phone>0046701671474</phone>
      <email>tomas.jernberg@sll.se</email>
    </contact>
    <investigator>
      <last_name>Tomas Jernberg, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska Institutet</investigator_affiliation>
    <investigator_full_name>Dr. Tomas Jernberg</investigator_full_name>
    <investigator_title>Co-ordinating principal investigator</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>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/NCT03278509
org study id: EudraCT number 2017-002336-17
nct id: NCT03278509
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Long-term beta-blocker therapy has not been investigated in contemporary randomized clinical
      trials in patients with myocardial infarction and normal heart function. The aim of this
      study is to determine whether long-term treatment with oral beta-blockade in patients with
      myocardial infarction and preserved left ventricular systolic ejection fraction reduces the
      composite of death of any cause or new myocardial infarction..
REDUCE-SWEDEHEART is designed as a registry-based, randomized, parallel, open-label,
      multicenter trial.

      Patients, day 1-7 after myocardial infarction, who have undergone a coronary angiography and
      with preserved left ventricular systolic ejection fraction will be randomized to either oral
      beta-blockade (see "Intervention" for detailed description) at a dose according to the
      treating physician, or no beta-blockade. To allow quick inclusion the randomization module
      will be accessible by a simple web-based log-in procedure. Concomitantly, all baseline data
      about each individual patient will be collected from the SWEDEHEART registry. Patients will
      then be followed regarding all-cause mortality, myocardial infarction, heart failure, atrial
      fibrillation, and patient-related outcome measures (for a subgroup of patients). Patients
      that are eligible but not included in REDUCE-SWEDEHEART will also be followed regarding
      chosen treatment and the primary and secondary endpoints.

      Follow-up will continue until 379 primary endpoints have been observed (endpoint driven). All
      analyses will be performed on the intention-to-treat set, defined as all intentionally
      randomized patients, by randomized treatment. The primary endpoint is death or new MI.
      Information about death will be obtained from the Swedish population registry. Information
      regarding new myocardial infarction during hospitalization and readmission because of
      myocardial infarction or other outcome (secondary outcomes, see section below), will be
      obtained from the SWEDEHEART-registry (for myocardial infarction) and the patient registry of
      the National board of health and welfare.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A registry-based, randomized, parallel, open-label, multicenter trial
primary purpose: Treatment
masking: None (Open Label)
measure: Time to the composite of death of any cause or MI
time frame: through study completion, an average of 3 year
description: Time to the composite of death of any cause or MI on an intention to treat basis (ITT)
measure: All-cause death
time frame: through study completion, an average of 3 year
description: Time to the individual component of the primary endpoint of any cause of death.
measure: Myocardial infarction
time frame: through study completion, an average of 3 year
description: Time to the individual component of the primary endpoint of MI.
measure: Cardiovascular death
time frame: through study completion, an average of 3 year
description: Time to cardiovascular death.
measure: Heart failure
time frame: through study completion, an average of 3 year
description: Time to hospital readmission due to heart failure (primary [main] diagnosis)
measure: Atrial fibrillation
time frame: through study completion, an average of 3 year
description: Time to hospital readmission due to atrial fibrillation (primary [main] diagnosis)
measure: Bradycardia, Advanced AV-block, hypotension, syncope or need for pacemaker
time frame: through study completion, an average of 3 year
description: Time to hospital readmission due to bradycardia or advanced AV-block or hypotension or syncope or need for pacemaker (primary [main] diagnosis)
measure: Asthma or Chronic Obstructive Pulmonary Disease
time frame: through study completion, an average of 3 year
description: Time to hospital readmission due to asthma or chronic obstructive pulmonary disease (primary [main] diagnosis)
measure: Stroke
time frame: through study completion, an average of 3 year
description: Time to hospital readmission due to stroke (primary [main] diagnosis)
measure: Health related quality of life (HRQOL)
time frame: Estimated maximal follow-up for each patient for this outcome is 1 year.
description: Health related quality of life (HRQOL) measured by EQ-5D in patients younger than 75 years of age
measure: Health care costs
time frame: through study completion, an average of 3 year
description: Health care cost analysis concerning the use beta-blocker treatment
measure: Anxiety and depression
time frame: 8 weeks and 12 months after randomization
description: Anxiety and depression measured by Hospital Anxiety and Depression Scale (HADS)
measure: Wellbeing
time frame: 8 weeks and 12 months after randomization
description: Wellbeing measured by WHO-5 Wellbeing Index
measure: Cardiac Anxiety
time frame: 8 weeks and 12 months after randomization
description: Cardiac Anxiety measured by Cardiac Anxiety Questionnaire (CAQ)
measure: Sexual function
time frame: 8 weeks and 12 months after randomization
description: Sexual function measured by Arizona Sexual Experiences Scale (ASEX)
arm group label: Oral beta-blocker treatment
arm group type: Experimental
description: Patients randomized to beta-blockade will be prescribed oral beta-blocker (metoprolol succinate or bisoprolol) at a dose according to the treating physician. Metoprolol succinate will be strongly recommended as first choice. Bisoprolol will be allowed as an alternative. Atenolol (or any other beta-blocker therapy) will not be allowed. The treating physician will be encouraged to aim for a dose of ≥ 100 mg for metoprolol succinate and ≥ 5 mg for bisoprolol. Prescribed treatment and dosing will be registered. Initiation (whether the prescribed drug is dispensed) and adherence (defined as proportion of prescribed tablets that are dispensed), and persistence (time on treatment) will also be recorded via the Drug prescription registry.
arm group label: No beta-blocker treatment
arm group type: No Intervention
description: Patients randomized to no beta-blockade will be discouraged to use beta-blockade as long as there is no other indication than strictly secondary prevention after myocardial infarction. Patients assigned to no beta-blockade also receive best evidence-based care, without beta-blockers. For blood pressure control, other drugs than beta-blockers will be recommended as first-line treatment. Regarding later use of beta-blockade, follow up is performed in the Drug prescription registry. Patients will be asked to provide future physicians with the written information about the study when beta-blockade treatment is discussed.
intervention type: Drug
intervention name: Metoprolol Succinate
description: Eligible patients randomized to active treatment will receive long-term oral beta-blockade (metoprolol succinate or bisoprolol).
arm group label: Oral beta-blocker treatment
intervention type: Drug
intervention name: Bisoprolol
description: Please see the section above.
arm group label: Oral beta-blocker treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tomas Jernberg, MD PhD
role: Principal Investigator
affiliation: Karolinska Institutet
last name: Bertil Lindahl, MD PhD
role: Study Chair
affiliation: Uppsala, Clinical Sciences
last name: Susanne Heller
phone: +46 18 611 95 00
email: susanne.heller@ucr.uu.se
last name: Troels Yndigegn, MD
phone: 0046732020045
email: troels.yndigegn@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Karolinska Institutet
investigator full name: Dr. Tomas Jernberg
investigator title: Co-ordinating principal investigator
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: Bisoprolol
sharing ipd: Undecided