BEtablocker Treatment After Acute Myocardial Infarction in Patients Without Reduced Left Ventricular Systolic Function
- Conditions
- Acute Myocardial InfarctionNon-ST Elevation Myocardial InfarctionST Elevation Myocardial Infarction
- Interventions
- Drug: BetablockerOther: Non-betablocker
- Registration Number
- NCT03646357
- Lead Sponsor
- Oslo University Hospital
- Brief Summary
The study aims to investigate whether oral betablocker (BB) therapy is superior to no such treatment following an acute myocardial infarction (AMI).
- 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 end point, the key secondary end points, and most other secondary end points will be analysed and published jointly with data from the 'Danish Trial of Beta-blocker therapy after myocardial infarction without heart failure' (DANBLOCK) (NCT 03778554) (please see below).
The primary objective is to test whether oral BB therapy reduces the risk of all-cause death, recurrent MI, incident heart failure, unplanned coronary revascularization, ischemic stroke, or malignant ventricular arrhythmia including resuscitated cardiac arrest of cardiac origin compared to no such therapy, in patients with AMI treated with PCI or thrombolysis without reduced LVEF.
The key secondary objectives (planned for the main study) 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\< 70 years vs. ≥70 years), gender sex (men vs. women), country (Denmark vs Norway), BB dosage tertiles (dosage at randomization (\<50 mg vs. ≥50 mg), hypertension (yes vs. no), diabetes (yes vs. no), diabetes (yes vs no), type of MI (STEMI vs. NSTEMI), and LVEF subgroups (preserved LVEF: ≥50% vs. mid-range LVEF: 40-49%).
* To study whether oral BB therapy increases the risk of hospitalization for second or third-degree atrioventricular block or implantation of pacemaker.
* To describe BB dosage and adherence at six months following randomization obtained from the national prescription registries
* To assess study safety
Other secondary objectives (for joint BETAMI-DANBLOCK sub-studies) 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 or syncope.
* 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 affects the following patient related outcomes:
quality of life, angina, dyspnoea, anxiety, depression, sexual dysfunction or sleep disorders
* To describe long term BB 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
Exploratory objectives (based on BETAMI data, only):
* 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 including resuscitated cardiac arrest of cardiac origin, 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 safety 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 May 2021 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), CAPITAL-RCT (NCT01155635) 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 2895
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Betablocker Betablocker Patients receiving a betablocker. Any other treatment or management is to be given as per usual care. Non-Betablocker Non-betablocker No betablocker is given to this arm. Any other treatment or management is to be given as per usual care.
- Primary Outcome Measures
Name Time Method A composite of death of any cause, recurrent myocardial infarction, incident heart failure, coronary revascularization, ischemic stroke, malignant ventricular arrhythmia including resuscitated cardiac arrest of cardiac origin 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
- Secondary Outcome Measures
Name Time Method Unplanned coronary revascularization 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
Measures of Nightmare Frequency Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months Nightmare Frequency Questionnaire
Ischemic stroke 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
Cardiovascular death 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
Hospitalization for stable and unstable angina 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
Measures of sexual dysfunction 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)
Recurrent MI 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
All-cause death 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
Hospitalization or outpatient consultation for incident heart failure 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
Malignant ventricular arrhythmias including resuscitated cardiac arrest of cardiac origin 6 months (minimum) to 6 years (maximum) Time to malignant ventricular arrhythmia including resuscitated cardiac arrest of cardiac origin from randomization. Estimated maximal follow-up for each patient for this outcome is 6 months to 6 years
Hospitalization for bradycardia, syncope or implantation of pacemaker 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
Hospitalization for chronic obstructive pulmonary disease, asthma or peripheral artery disease 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
Hospitalization for atrial fibrillation, atrial flutter or other atrial tachyarrhythmias 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
Angina symptoms Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months Canadian Cardiovascular Society (CCS) grading of angina pectoris.
Health-related quality of life 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
Measures of sleep disorders Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months Bergen insomnia Scale and sleep duration
Measures of depression and anxiety Through self-report questionnaires administered at inclusion, 30 days, 3,6 and 18 months HADS (Hospital Anxiety and Depression Scale)
Trial Locations
- Locations (20)
Sørlandet Sykehus
🇳🇴Arendal, Norway
Haukeland Universitetssykehus
🇳🇴Bergen, Norway
Nordlandssykehuset HF Bodø
🇳🇴Bodø, Norway
Drammen Hospital
🇳🇴Drammen, Norway
Sykehuset Østfold Kalnes
🇳🇴Fredrikstad, Norway
Sykehuset Innlandet HF, Gjøvik Sykehus
🇳🇴Gjøvik, Norway
Sykehuset Innlandet Hamar
🇳🇴Hamar, Norway
Vestre Viken HF, Ringerike Sykehus
🇳🇴Hønefoss, Norway
Sykehuset Innlandet Lillehammer
🇳🇴Lillehammer, Norway
AHUS
🇳🇴Lørenskog, Norway
Scroll for more (10 remaining)Sørlandet Sykehus🇳🇴Arendal, Norway