- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03646357
BEtablocker Treatment After Acute Myocardial Infarction in Patients Without Reduced Left Ventricular Systolic Function (BETAMI)
BEtablocker Treatment After Acute Myocardial Infarction in Patients Without Reduced Left Ventricular Systolic Function (BETAMI)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a prospective, randomized, open blinded end-point (PROBE) study. Patients with AMI will be randomized 1-8 days following PCI or thrombolysis, and allocated to either prescription of a BB or to no such prescription. Subjects will be followed up for at least 6 months (median 3 years) with respect to the primary and secondary endpoints.
The primary objective is to test whether oral BB therapy reduces the risk of all-cause death, recurrent MI, incident heart failure, coronary revascularization, ischemic stroke, malignant ventricular arrhythmia or resuscitated cardiac arrest compared to no such therapy, in patients with AMI treated with PCI or thrombolysis without reduced LVEF.
The key secondary objectives are:
- To study whether oral BB therapy reduces the risk of each of the components of the primary end-point separately, compared to no such therapy
- To assess clinical outcomes linked BB therapy in the following subgroups: age (tertiles), gender (men vs. women), BB dosage tertiles (dosage at randomization, STEMI vs. NSTEMI, and LVEF subgroups (preserved LVEF: ≥50% vs. mid-range LVEF: 40-49%).
Other secondary objectives are:
- To study whether oral BB therapy reduces the risk of cardiovascular death compared to no such therapy
- To study whether oral BB therapy reduces the risk of stable and unstable angina compared to no such therapy
- To study whether oral BB therapy reduces the risk of atrial fibrillation, atrial flutter or other atrial tachyarrhythmias compared to no such therapy
- To study whether oral BB therapy increases the risk of hospitalization for bradycardia, syncope, implantation of pacemaker.
- To study whether oral BB therapy increases the risk of hospitalization for chronic obstructive pulmonary disease, asthma or peripheral artery disease.
- To study whether oral BB therapy increases the risk of hospitalization or outpatient visit for new-onset or dysregulated diabetes
- To study whether oral BB therapy affects the following patient related outcomes:
quality of life, angina, dyspnoea, anxiety, depression, sexual dysfunction or sleep disorders
- To describe BB dosage and adherence obtained from the national prescription registries
- To study sociodemographic, clinical, and psychosocial characteristics (PROMS and clinical data) between the two study arms and in the total sample
- To conduct cost-utility analysis in relation to quality of life and a health economic evaluation including drug use, health care utilization, employment, income, and benefit take-up
- To assess study safety
Exploratory objectives:
- To study the proportion and predictors of non-adherence with BB, statins and other cardiovascular drugs assessed by direct methods quantifying drug concentrations in blood
- Identify pharmacokinetic, pharmacogenetic and pharmacodynamic markers associated with side-effects and suboptimal response to treatment with cardiovascular drugs
The primary study end-points will be obtained through linkage to the Norwegian Cardiovascular Disease Registry and The Norwegian Population Registry (Folkeregisteret)
Secondary endpoints will be obtained by linkage to the following national registries: The Norwegian Population Registry (Folkeregisteret), the Cause of Death Registry, the Norwegian Patient Registry, the Norwegian Cardiovascular Disease Registry, the Norwegian Prescription Database, the Norwegian registry for income, the FD-Trygd database (social security micro data for research) and the Control and payment of reimbursements to health service providers (KUHR) database. Further by collecting self-reported questionnaires and a clinical examination with blood sample collection.
Primary safety endpoints:
• To describe the composite endpoint of malignant ventricular arrhythmias or resuscitated cardiac arrest, incident heart failure, new MI or all-cause death at 30 days after randomization collected from i. direct telephone contact with the patient and from hospital medical records, ii. linkage to the Norwegian Cardiovascular Disease Registry and The Norwegian Population Registry at study end.
Other safery endpoints:
- To describe all-cause death at study end
- To describe Suspected Unexpected Serious Adverse Reaction (SUSARs) during the follow-up period from the study database (continously reported by local investigators).
Rationale for combining data from the BETAMI study with the DANBLOCK (NCT03778554) study from Denmark: The trials have similar designs, only minor differences in study entry criteria, and were, from the very beginning, coordinated with the aim of conducting sub-studies on pooled data. However, the inclusion- and event rates have been lower than expected in both studies. To enhance feasibility, the final decision was made from both Steering Committees in March 2022 to combine the trials and publish initial results jointly. BETAMI and DANBLOCK will remain separate trials until the end of follow-up, where data from the trials will be combined and main results published together.
Sample size: A total of approximately 2900 patients from BETAMI will be recruited and randomized 1:1 to BB treatment (type and dosage according to treating physician) or no BB treatment within 8 days of MI. The study is event driven and a power calculation for the combined DANBLOCK-BETAMI trial has been performed in which 950 events will provide a power of 80% to detect a true treatment effect equal to a hazard ratio of 1.2 for no beta-blocker therapy. Follow-up: Patients will be followed from the randomization date until end of follow-up. The last patient included will be followed for a minimum of 6 months. Estimated mean (non) treatment duration is 3 (0.5-6) years.
Post-trial objective:
• To perform a joint analysis of the data from BETAMI-DANBLOCK with the REDUCE (NCT03278509) and REBOOT (NCT03596385) trials. This analysis will comprise approximately 19000 patients, giving increased power and precision for clinical decisions on both primary and secondary endpoints.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: John Munkhaugen, MD PhD
- Phone Number: +4797524194
- Email: johmun@vestreviken.no
Study Contact Backup
- Name: Arnhild Bakken, MD PhD
- Email: arnhild.bakken@ous-hf.no
Study Locations
-
-
-
Arendal, Norway
- Sørlandet sykehus
-
Bergen, Norway
- Haukeland Universitetssykehus
-
Bodø, Norway
- Nordlandssykehuset HF Bodø
-
Drammen, Norway
- Drammen Hospital
-
Fredrikstad, Norway
- Sykehuset Østfold Kalnes
-
Gjøvik, Norway
- Sykehuset Innlandet HF, Gjøvik Sykehus
-
Hamar, Norway
- Sykehuset Innlandet Hamar
-
Hønefoss, Norway
- Vestre Viken HF, Ringerike Sykehus
-
Lillehammer, Norway
- Sykehuset Innlandet Lillehammer
-
Lørenskog, Norway
- AHUS
-
Lørenskog, Norway
- LHL Gardermoen
-
Oslo, Norway
- Lovisenberg Diakonale Sykehus
-
Oslo, Norway
- Diakonhjemmet Sykehus
-
Oslo, Norway
- Oslo University Hospital Rikshospitalet, Dept.of Cardiology
-
Oslo, Norway
- Oslo University Hospital Ullevaal, Dept. of Cardiology
-
Sandvika, Norway
- Vestre Viken HF, Bærum Sykehus
-
Stavanger, Norway
- Stavanger universitetssjukehus
-
Tromsø, Norway
- Universitetssykehuset Nord-Norge, UNN
-
Trondheim, Norway
- St. Olavs University Hospital
-
Tønsberg, Norway
- Vestfold hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria
To be eligible for inclusion in the study, subjects must fulfill the following criteria at inclusion:
- 18 years or older
- Diagnosed with an acute MI type I according to the "Universal Definition of MI" (Defined as a detection of a rise and/or fall of cardiac biomarker value, preferably troponin, with at least one value above the 99th percentile upper reference limit and with at least one of the following; a) symptoms of ischemia, b) new or presumed new significant ST-segment-T wave changes or new left bundle branch block, c) development of pathological Q waves, d) imaging evidence of new loss of viable myocardium or e) identification of an intracoronary thrombus by coronary angiogram)
- Must have been treated with PCI or thrombolysis during current hospitalization
- Signed informed consent and expected cooperation of the patient according to ICH/GCP and national/local regulations
- Have a national personal identification number and not be expected to emigrate during study
Exclusion Criteria
Study subjects must not meet any of the following criteria:
Having a condition where betablocker-therapy is required, including but not limited to:
- Arrhythmias
- Hypertension
- Cardiomyopathies
- Clinical diagnosis of heart failure
- LVEF < 40% by echocardiography (by measurement and not only visual assessment for STEMI patients)
- Left ventricular akinesia in ≥ 3 segments regardless of the LVEF
Contraindications to betablocker-therapy, including but not limited to:
- Bradyarrhythmias
- Hypotension
- Severe peripheral artery disease
- Previously known side-effects causing withdrawal
- Severe chronic obstructive pulmonary disease
- • Women of childbearing potential (a woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile)
- Known hypersensitivity to any ingredient of the IMP
- Other, according to the responsible investigator
- End-stage somatic disease with short life expectancy, dementia, psychosis and other conditions could put the subject at significant risk, confound the study results, interfere significantly with the subject participation in the study, or rendering informed consent unfeasible
Previous treatment with a betablocker is not an exclusion criterion for enrollment into the BETAMI study. Enrolled patients can participate in any other study that does not directly alter the effect betablocker treatment
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Betablocker
Patients receiving a betablocker.
Any other treatment or management is to be given as per usual care.
|
A betablocker will be administered. To reflect contemporary management, for which this study is designed to test, there will not be a defined minimum dosage. The type and dose of BB will be left at the discretion of the PI. Generic drug and accepted dosages will be:
The treating physician will be encouraged to aim for an equipotent dose of 100 mg metoprolol succinate or higher. Any other treatment or management is to be given as per usual care. |
Experimental: Non-Betablocker
No betablocker is given to this arm.
Any other treatment or management is to be given as per usual care.
|
No betablocker will be administered.
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.
Any other treatment or management is to be given as per usual care.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
A composite of death of any cause, recurrent myocardial infarction, incident heart failure, coronary revascularization, ischemic stroke, malignant ventricular arrhythmia or resuscitated cardiac arrest
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Incidence of combined endpoint from randomization.
Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Recurrent MI
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Time to recurrent MI from randomization.
Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
All-cause death
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Time to a-cause Death from randomization.
Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
Malignant ventricular arrhythmia
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Time to malignant ventricular arrhythmia from randomization.
Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
Hospitalization or outpatient consultation for incident heart failure
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Time to hospitalization or outpatient consultation for heart failure from randomization.
Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
Unplanned coronary revascularization
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Time to unplanned coronary revascularization from randomization.
Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
Ischemic stroke
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Time to ischemic stroke from randomization.
Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
Resuscitated cardiac arrest
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Time to resuscitated cardiac arrest from randomization.
Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
Cardiovascular death
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Time to cardiovascular death from randomization.
Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
Hospitalization for stable and unstable angina
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Time to hospitalization for stable and unstable angina from randomization.
Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
Hospitalization for atrial fibrillation, atrial flutter or other atrial tachyarrhythmias
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Time to hospitalization for atrial fibrillation, atrial flutter or other atrial tachyarrhythmias from randomization.
Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
Hospitalization for bradycardia, syncope or implantation of pacemaker
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Time to hospitalization for bradycardia, syncope or implantation of pacemaker from randomization.
Estimated maximal follow-up for each patient for this outcome I 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
Hospitalization for chronic obstructive pulmonary disease, asthma or peripheral artery disease
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Time to hospitalization for chronic obstructive pulmonary disease, asthma or peripheral artery disease from randomization.
Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
Hospitalization or outpatient visit for new-onset or dysregulated diabetes
Time Frame: 6 months (minimum) to 6 years (maximum)
|
Time to hospitalization hospitalization or outpatient visit for new-onset or dysregulated diabetes from randomization.
Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
|
6 months (minimum) to 6 years (maximum)
|
Angina symptoms
Time Frame: Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
Canadian Cardiovascular Society (CCS) grading of angina pectoris.
|
Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
Health-related quality of life
Time Frame: Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
Health-related quality of life measured by the Short Form (SF) 12
|
Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
Measures of depression and anxiety
Time Frame: Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
HADS (Hospital Anxiety and Depression Scale)
|
Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
Measures of sexual dysfunction
Time Frame: Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
The International Index of Erectile Function (IIEF) and Female Sexual Function Index (FSFI)
|
Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
Measures of sleep disorders
Time Frame: Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
Bergen insomnia Scale
|
Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
Measures of sleep disorders
Time Frame: Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
Bergen insomnia Scale and sleep duration
|
Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
Measures of Nightmare Frequency
Time Frame: Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
Nightmare Frequency Questionnaire
|
Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Dan Atar, MD Prof, Oslo University Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Ischemia
- Pathologic Processes
- Necrosis
- Myocardial Ischemia
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Myocardial Infarction
- Infarction
- ST Elevation Myocardial Infarction
- Non-ST Elevated Myocardial Infarction
- Physiological Effects of Drugs
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Adrenergic beta-Antagonists
Other Study ID Numbers
- 2018-000590-75
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on ST Elevation Myocardial Infarction
-
Azienda ULSS 5 PolesanaUniversity of PadovaUnknownMyocardial Infarction, Acute | ST Segment Elevation Myocardial Infarction | Non-ST Elevation Myocardial Infarction (nSTEMI)Italy
-
Stiftung Institut fuer HerzinfarktforschungGlaxoSmithKline; University Hospital Muenster; Klinikum NürnbergCompletedMyocardial Infarction | ST-Elevation Myocardial Infarction | Non-ST-Elevation Myocardial InfarctionGermany
-
University of LeedsUniversity College, LondonCompletedST-elevation Myocardial Infarction | Non ST-elevation Myocardial Infarction
-
University Medical Centre LjubljanaCompletedCardiac Arrest | Postresuscitation Syndrome | Myocardial Infarction (ST-Elevation Myocardial Infarction and Non-ST-Elevation Myocardial Infarction)Slovenia
-
Inha University HospitalCompletedST Segment Elevation Myocardial Infarction | Non-ST Segment Elevation Myocardial InfarctionKorea, Republic of
-
Population Health Research InstituteCanadian Institutes of Health Research (CIHR); Boston Scientific CorporationActive, not recruitingST Elevation Myocardial Infarction | Non ST Elevation Myocardial InfarctionCanada
-
RenJi HospitalCompletedST Segment Elevation Myocardial Infarction
-
Dong-A UniversityTerminatedST-Segment Elevation Myocardial InfarctionKorea, Republic of
-
Azienda Ospedaliera San Camillo ForlaniniUnknownST Segment Elevation Myocardial InfarctionItaly
-
Jinan Central HospitalUnknownST-Segment Elevation Myocardial InfarctionChina
Clinical Trials on Betablocker
-
Postgraduate Institute of Medical Education and...RecruitingPortal Hypertension | Cirrhosis, Liver | Left Ventricular Dysfunction | Cirrhotic CardiomyopathyIndia
-
University Hospital, ToulouseCompleted
-
Niels JunkerKarolinska University Hospital; Oslo University Hospital; Aarhus University HospitalRecruitingSoft Tissue Sarcoma Adult | Angiosarcoma | Undifferentiated Pleomorphic SarcomaNorway, Sweden, Denmark
-
Policlinico Casilino ASL RMBWithdrawnHeart Rate Control in ICD Patients With Heart FailureItaly
-
Maastricht University Medical CenterCompletedPreeclampsia | HELLP Syndrome | Small for Gestational Age at DeliveryNetherlands
-
Sorlandet Hospital HFOslo University HospitalCompleted
-
Sao Jose do Rio Preto Medical SchoolCompletedHypertension Resistant to Conventional TherapyBrazil
-
Nantes University HospitalNot yet recruiting