BEtablocker Treatment After Acute Myocardial Infarction in Patients Without Reduced Left Ventricular Systolic Function — BETAMI  

Acute Myocardial Infarction Clinical Trial

Official title: BEtablocker Treatment After Acute Myocardial Infarction in Patients Without Reduced Left Ventricular Systolic Function (BETAMI)

Status Active, not recruiting

Clinical Trial Summary

The study aims to investigate whether oral betablocker (BB) therapy is superior to no such treatment following an acute myocardial infarction (AMI).

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction
• Non-ST Elevated Myocardial Infarction
• Non-ST Elevation Myocardial Infarction
• ST Elevation Myocardial Infarction

• NCT number: NCT03646357
• Study type: Interventional
• Source: Oslo University Hospital
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: October 1, 2018
• Completion date: December 10, 2034