ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of Decreased Usage of Betablockers After Myocardial Infarction in the SWEDEHEART Registry (REDUCE-SWEDEHEART)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03278509
Recruitment Status : Recruiting
First Posted : September 11, 2017
Last Update Posted : August 14, 2018
Sponsor:
Collaborators:
Uppsala University
The Swedish Research Council
Information provided by (Responsible Party):
Dr. Tomas Jernberg, Karolinska Institutet

Brief Summary:
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..

Condition or disease Intervention/treatment Phase
Acute Myocardial Infarction Non-ST Elevation Myocardial Infarction ST Elevation Myocardial Infarction Drug: Metoprolol Succinate Drug: Bisoprolol Phase 4

Detailed Description:

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 944 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 7000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A registry-based, randomized, parallel, open-label, multicenter trial
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 11, 2017
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : August 31, 2025


Arm Intervention/treatment
Experimental: Oral beta-blocker treatment
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.
Drug: Metoprolol Succinate
Eligible patients randomized to active treatment will receive long-term oral beta-blockade (metoprolol succinate or bisoprolol).

Drug: Bisoprolol
Please see the section above.

No Intervention: No beta-blocker treatment
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.



Primary Outcome Measures :
  1. Time to the composite of death of any cause or MI [ Time Frame: Event-driven study. Estimated maximal follow-up for each patient for this outcome is 1-3 years. ]
    Time to the composite of death of any cause or MI on an intention to treat basis (ITT)


Secondary Outcome Measures :
  1. All-cause death [ Time Frame: Estimated maximal follow-up for each patient for this outcome is 1-3 years. There will be a second analysis after follow up for 3-5 years. ]
    Time to the individual component of the primary endpoint of any cause of death.

  2. Myocardial infarction [ Time Frame: Estimated maximal follow-up for each patient for this outcome is 1-3 years. ]
    Time to the individual component of the primary endpoint of MI.

  3. Cardiovascular death [ Time Frame: Estimated maximal follow-up for each patient for this outcome is 1-3 years. ]
    Time to cardiovascular death.

  4. Heart failure [ Time Frame: Estimated maximal follow-up for each patient for this outcome is 1-3 years. ]
    Time to hospital readmission due to heart failure (primary [main] diagnosis)

  5. Atrial fibrillation [ Time Frame: Estimated maximal follow-up for each patient for this outcome is 1-3 years. ]
    Time to hospital readmission due to atrial fibrillation (primary [main] diagnosis)

  6. Bradycardia, Advanced AV-block, hypotension, syncope or need for pacemaker [ Time Frame: Estimated maximal follow-up for each patient for this outcome is 1-3 years. ]
    Time to hospital readmission due to bradycardia or advanced AV-block or hypotension or syncope or need for pacemaker (primary [main] diagnosis)

  7. Asthma or Chronic Obstructive Pulmonary Disease [ Time Frame: Estimated maximal follow-up for each patient for this outcome is 1-3 years. ]
    Time to hospital readmission due to asthma or chronic obstructive pulmonary disease (primary [main] diagnosis)

  8. Stroke [ Time Frame: Estimated maximal follow-up for each patient for this outcome is 1-3 years. ]
    Time to hospital readmission due to stroke (primary [main] diagnosis)

  9. Health related quality of life (HRQOL) [ Time Frame: Estimated maximal follow-up for each patient for this outcome is 1 year. ]
    Health related quality of life (HRQOL) measured by EQ-5D in patients younger than 75 years of age

  10. Health care costs [ Time Frame: Estimated maximal follow-up for each patient for this outcome is 1-3 years. ]
    Health care cost analysis concerning the use beta-blocker treatment


Other Outcome Measures:
  1. Anxiety and depression [ Time Frame: 8 weeks and 12 months after randomization ]
    Anxiety and depression measured by Hospital Anxiety and Depression Scale (HADS)

  2. Wellbeing [ Time Frame: 8 weeks and 12 months after randomization ]
    Wellbeing measured by WHO-5 Wellbeing Index

  3. Cardiac Anxiety [ Time Frame: 8 weeks and 12 months after randomization ]
    Cardiac Anxiety measured by Cardiac Anxiety Questionnaire (CAQ)

  4. Sexual function [ Time Frame: 8 weeks and 12 months after randomization ]
    Sexual function measured by Arizona Sexual Experiences Scale (ASEX)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age≥18 years.
  2. Day 1-7 after MI as defined by the universal definition of MI, type 1, included in the SWEDEHEART registry.
  3. Undergone coronary angiography during hospitalization.
  4. Obstructive coronary artery disease documented by coronary angiography, i.e. stenosis ≥ 50 %, FFR ≤ 0.80 or iFR ≤ 0.89 in any segment at any time point before randomization.
  5. Echocardiography performed after the MI showing a normal ejection fraction (EF≥50%).
  6. Written informed consent obtained.

Exclusion Criteria:

  1. Any condition that may influence the patient's ability to comply with study protocol.
  2. Contraindications for beta-blockade
  3. Indication for beta-blockade other than as secondary prevention according to the treating physician.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03278509


Contacts
Contact: Eva Jacobsson, PhD 004618-611 95 00 eva.jacobsson@ucr.uu.se
Contact: Troels Yndigegn, MD 0046732020045 troels.yndigegn@gmail.com

Locations
Sweden
Danderyd Hospital, Cardiac Intensive Care Recruiting
Danderyd, Stockholms Län, Sweden, 182 88
Contact: Tomas Jernberg, MD, PhD    0046701671474    tomas.jernberg@sll.se   
Principal Investigator: Tomas Jernberg, MD, PhD         
Sponsors and Collaborators
Karolinska Institutet
Uppsala University
The Swedish Research Council
Investigators
Principal Investigator: Tomas Jernberg, MD PhD Karolinska Institutet
Study Chair: Bertil Lindahl, MD PhD Uppsala, Clinical Sciences

Responsible Party: Dr. Tomas Jernberg, Co-ordinating principal investigator, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT03278509     History of Changes
Other Study ID Numbers: EudraCT number 2017-002336-17
First Posted: September 11, 2017    Key Record Dates
Last Update Posted: August 14, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
ST Elevation Myocardial Infarction
Non-ST Elevated Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Metoprolol
Bisoprolol
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action