DANBLOCK: Danish Trial of Beta Blocker Treatment After Myocardial Infarction Without Reduced Ejection Fraction
Study Details
Study Description
Brief Summary
To determine whether long-term treatment with oral betablocker (BB) therapy after myocardial infarction (MI) in patient with no heart failure reduces the composite outcome of death from any cause, recurrent MI, unstable angina pectoris, stroke or heart failure.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Aim: To determine whether long-term treatment with oral betablocker (BB) therapy after myocardial infarction (MI) in patient with no heart failure reduces the composite outcome of death from any cause, recurrent MI, unstable angina pectoris, stroke or heart failure.
Intervention: BB therapy versus no therapy.
Main Inclusion Criteria: Patient that have suffered a MI, both Non-ST elevation MI and ST elevation MI and can be randomized within 14 days of MI with no signs of heart failure and a left ventricular ejection fraction>40%.
Main Exclusion Criteria: Any indication or contraindication for BB treatment other than secondary prevention according to the treating cardiologist
Primary study endpoint: The composite of all-cause mortality, recurrent non-fatal MI, unstable angina pectoris, stroke or heart failure
Sample Size: A total of 3570 patients will be recruited and randomized 1:1 to BB treatment (type and dosage according to treating physician) or no BB treatment. Treatment must be initiated within 14 days of MI.
Location: All departments of cardiology in Denmark are invited to participate. All patients admitted to hospital for MI will be screened for in- and exclusion criteria and contacted if eligible.
Treatment Duration: Estimated (non) treatment duration of 2-4 years. Follow-up: Patients will be followed from the randomization date until end of follow-up with respect to the primary and most secondary endpoints.
Assessment of primary study and safety end points: Serious adverse events (SAE) will be monitored through patient reported hospital admission by surveys every 3 months combined with local follow-up on patients that do not respond to surveys
Intervention and dosage of BB treatment: The intervention will be active treatment with BB, type and dosage according to treating cardiologist choice and control will be standard care (without BB treatment). The treating cardiologist is recommended to use the highest dose deemed tolerable for the patient at the time of randomization. Dosage, adherence and cross-over will be monitored through linkage to the Danish Register of Medical Product Statistics.
Sample size considerations: Assuming a hazard ratio of 1.2 for the non-treated group compared to the treated the DANBLOCK trial has 80% power to detect this effect with an accumulation of 900 events of the primary endpoint. With 3570 patients randomized the investigators expect to reach 900 events within the study period.
Statistical Analysis: Intention-to-treat analysis will be carried out. Additionally, a secondary per-protocol analysis will be performed, where compliant BB-users patients are considered exposed during follow-up. Outcome analysis will be assessed by using cumulative incidence and Cox-regressions.
Data Safety Monitoring Board (DSMB): This committee consisting of two senior cardiologists and one trial-science statistician will overview safety and will have access to unblinded data. They will formally review the accumulating data every 6 months throughout the study period to ensure there is no avoidable increased harm to patients. The DSMB may recommend trial termination due to excess risk associated with no treatment with BB.
Recruitment: All patients admitted to hospital for MI will be screened for in- and exclusion criteria and contacted if eligible. Logistics of identifying and contacting the patients will be organized locally; some hospitals will randomize patients before discharge, others will contact patients after discharge. Patients will be randomized 1:1.
Publication policy: On study completion the results will be submitted for publication in an international medical journal. The results of this study will also be submitted to the Competent Authority and the Ethics Committee according to EU and Danish regulations.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Beta blocker treatment Treatment with beta blockers plus standard of care. Type and dosage according to treating cardiologist choice Bisoprolol up to a total dose of 10 mg daily Carvedilol up to a total dose of 50 mg daily Metoprolol succinate up to a total dose of 200 mg daily Nebivolol up to a total dose of 10 mg daily |
Drug: Metoprolol Succinate
Eligible patients randomized to receive long-term therapy with oral beta-blockade
Drug: Bisoprolol
Eligible patients randomized to receive long-term therapy with oral beta-blockade
Drug: Carvedilol
Eligible patients randomized to receive long-term therapy with oral beta-blockade
Drug: Nebivolol
Eligible patients randomized to receive long-term therapy with oral beta-blockade
|
| No Intervention: No beta blocker treatment Standard care without beta blocker treatment |
Outcome Measures
Primary Outcome Measures
- The composite endpoint of all-cause mortality, hospital admission for recurrent myocardial infarction, unstable angina, stroke and heart failure [Estimated maximal follow-up 2-4 years]
Time to the composite of all-cause mortality, hospital admission for recurrent myocardial infarction, unstable angina, stroke or heart failure on an intention to treat analysis. The composite outcome will be assessed through nationwide registries.
Secondary Outcome Measures
- The incidence of cardiovascular mortality [Estimated maximal follow-up 2-4 years]
Time to cardiovascular mortality assessed through nationwide registries.
- The incidence of atrial fibrillation/atrial flutter [Estimated maximal follow-up 2-4 years]
Time to hospital admission of the outcome assessed through nationwide registries.
- The incidence of cardiac arrest [Estimated maximal follow-up 2-4 years]
Time to cardiac arrest assessed through nationwide registries.
- The incidence of ventricular arrhythmias [Estimated maximal follow-up 2-4 years]
Time to hospital admission of the outcome assessed through nationwide registries.
- Angina symptoms [Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months]
Canadian Cardiovascular Society (CCS) grading of angina pectoris.
- Exercise capacity [After 24 months and at study end.]
Data on exercise capacity (VO2peak) will measured before and after rehabilitation and recorded in the Danish Cardiac Rehabilitation database after 24 months and at study end. This data is only available for patients participating in cardiac rehabilitation.
- The incidence of bradycardia, syncope or need for pacemaker [Estimated maximal follow-up 2-4 years]
Time to hospital admission of the outcome assessed through nationwide registries.
- The incidence of asthma and chronic obstructive pulmonary disease symptoms [Estimated maximal follow-up 2-4 years]
Time to hospital admission of the outcome assessed through nationwide registries.
- Blood pressure control [After 24 months and at study end.]
Data on blood pressure (systolic and diastolic ) will measured before and after rehabilitation and recorded in the Danish Cardiac Rehabilitation database after 24 months and at study end. This data is only available for patients participating in cardiac rehabilitation.
- Diabetes (new diagnosis and dysregulation) [After 24 months and at study end.]
Data on diabetes (new diagnosis and dysregulation) will measured through hba1c before and after rehabilitation and recorded in the Danish Cardiac Rehabilitation database after 24 months and at study end. This data is only available for patients participating in cardiac rehabilitation.
- The incidence of peripheral artery disease [Estimated maximal follow-up 2-4 years]
Time to hospital admission of the outcome assessed through nationwide registries.
- The incidence of heart failure [Estimated maximal follow-up 2-4 years]
Time to hospital admission of the outcome assessed through nationwide registries.
- The incidence of mortality [Estimated maximal follow-up 2-4 years]
Time to all-cause mortality assessed through nationwide registries.
- The incidence of myocardial infarction [Estimated maximal follow-up 2-4 years]
Time to hospital admission of the outcome assessed through nationwide registries.
- The incidence of unstable angina pectoris [Estimated maximal follow-up 2-4 years]
Time to hospital admission of the outcome assessed through nationwide registries.
- The incidence of stroke [Estimated maximal follow-up 2-4 years]
Time to hospital admission of the outcome assessed through nationwide registries.
- Quality of life measure [Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months]
EQ5D (a measure of health-related quality of life that can be used in a wide range of health conditions and treatments)
- Measures of depression and anxiety [Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months]
HADS (Hospital Anxiety and Depression Scale)
- Measures of sexual dysfunction [Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months]
The International Index of Erectile Function (IIEF) and Female Sexual Function Index (FSFI)
- Measures of sleeping disorder [Through e-questionnaires will be administered at inclusion, 3, 12 and 24 months]
Bergen insomnia Scale
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Left ventricular ejection fraction > 40%
-
Myocardial infarction (MI) within previous two weeks
The diagnosis of acute MI must meet the Universal European Society of Cardiology (ESC) definition of MI
Exclusion Criteria:
-
Clinical evidence of heart failure at the time of discharge
-
Pregnancy or of child bearing age not using safe anticonception throughout the study period
-
Lack of signed informed consent and expected cooperation during follow-up
-
Any medical condition where beta blocker treatment is indicated according to the treating physician
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Bispebjerg Hospital, Dept. of Cardiology Y builing 67, 1.floor, Bispebjerg Bakke 23 | Copenhagen | Denmark | 2400 |
Sponsors and Collaborators
- Bispebjerg Hospital
- Amager Hospital
- Bispebjerg Frederiksberg Hospital
- Bornholm Hospital
- Gentofte Hospital
- Glostrup University Hospital, Copenhagen
- Herlev Hospital
- Hvidovre University Hospital
- Nordsjaelland Hospital
- Holbaek Hospital
- Nykoebing Hospital
- Naestved Hospital
- Nordsjaellands Hospital
- Zealand University Hospital
- Slagelse Hospital
- Odense University Hospital
- Svendborg Hospital
- Sydvestjysk Sygehus
- Hospital of Southern Jutland
- Sygehus Lillebaelt (Vejle and Kolding)
- Aarhus Universitetshospital
- Hospitalsenheden Midt
- Hospitalsenheden Vest
- Regionshospitalet Horsens
- Silkeborg Sygehus
- Aalborg University Hospital
Investigators
- Principal Investigator: Eva IB Prescott, MD, DMsC, Bispebjerg Frederiksberg University Hospital
- Study Chair: Thomas SG Sehested, MD, Bispebjerg Frederiksberg Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2018-002699-42
- 2018-002699-42