Coronary Arterial Disease (CAD), Ischemic Heart Disease (IHD)
Conditions
Keywords
Cardiac computed tomography, premedication, metoprolol, ivabradine, atenolol, heart rate control, heart rate
Brief summary
The goal of this clinical trial is to describe which type and dose of commonly used heart rate reducing drugs (metoprolol, atenolol, or ivabradine) has the swiftest heart rate reduction from baseline in patients aged 30 to 80 years with a heart rate \> 65 beats per minute undergoing cardiac computed tomography for the evaluation of coronary artery disease. The main question it aims to answer is • Which type of heart reducing drug and dose has the swiftest heart rate reduction before cardiac computed tomography?
Detailed description
This single-center, prospective, randomized, double-blind, clinical trial will include patients undergoing cardiac computed tomography. Two phases will be conducted: a pilot study (dose-finding phase) and a randomized trial (superiority phase). In the first dose-finding phase participants (N=150) will be randomized 1:1 in six arms (arms contain lower and higher doses of atenolol, metoprolol and ivabradine). Following an interim analysis, a superiority phase will be conducted using two parallel groups, non-diabetics (N=100) and diabetics (N=100), in a placebo-controlled head-to-head randomized 2:2:1 three-arms trial comparing the fastest betablocker and dose and the fastest dose of ivabradine from the dose-finding phase.
Interventions
DRUGatenolol
No studies have compared metoprololtartrat, ivabradine, atenolol and placebo in different doses as drugs before cardiac computed tomography
No studies have compared metoprololtartrat, ivabradine, atenolol and placebo in different doses as drugs before cardiac computed tomography
DRUGIvabradine
No studies have compared metoprololtartrat, ivabradine, atenolol and placebo in different doses as drugs before cardiac computed tomography
DRUGAtenolol/Metoprolol tartrate
No studies have compared metoprololtartrat, ivabradine, atenolol and placebo in different doses as drugs before cardiac computed tomography
DRUGIvabradine 7.5/15 mg
No studies have compared metoprololtartrat, ivabradine, atenolol and placebo in different doses as drugs before cardiac computed tomography
Sponsors
Department of Cardiology, Gødstrup Hospital, Herning, Denmark
Gødstrup Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Initial dose-finding pilot study using a controlled, double-blind, 6 armed 1:1 randomized design. Followed by a sequential controlled, double-blind, placebo-controlled study of most effective betablocker and ivabradine dose among a subgroup of diabetics and non-diabetics undergoing cardiac computed tomography.
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Individuals who are to undergo Cardiac CT * Sinus rhythm with heart rate \> 65 bpm on ECG * Competent patients who have given written informed consent
Exclusion criteria
* Age \> 80 years * Age \< 30 years * Heart rate \> 100 bpm * BMI \> 35 * Previous percutaneous coronary intervention (with or without stent) * Previous CABG * Known ischemic heart disease * Pacemaker * Acute coronary syndrome * Known allergy to beta-blockers * Known allergy to ivabradine * Known allergy to used radiographic contrast agents * Pregnant, including potentially pregnant, or breastfeeding (potentially pregnant patients will undergo pregnancy testing) * Heart failure with systolic left ventricular ejection fraction \< 45% * Reduced kidney function with estimated glomerular filtration rate (eGFR) \< 40 ml/min * Regular treatment with beta-blockers * Regular treatment with ivabradine * Regular treatment with non-dihydropyridine calcium antagonists (Verapamil and Diltiazem) * Regular treatment with Cordarone * Contraindications for beta-blockers or ivabradine: * Severe asthma * Severe COPD * Sick sinus syndrome * Sinoatrial block (1st degree AV block) * Advanced AV block (2nd or 3rd degree) * Hypotension (systolic blood pressure \< 110 mmHg) * Severe heart failure * Severe restrictive cardiomyopathy * Severe aortic stenosis * Severe circulatory disturbances * Severe metabolic conditions * Untreated pheochromocytoma * Concurrent treatment with potent inhibitors of CYP3A4 * Concurrent treatment with potent inhibitors of MAO inhibitors, * Concurrent treatment with potent inhibitors of CYP2D6 inhibitors * Concurrent treatment with potent inhibitors of intravenous calcium antagonists type I or III
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose and type of drugs with the swiftest heart rate reduction in patients undergoing cardiac computed tomography | From adminstration of study drug to start af cardiac computed tomography, 2 hours | Time in minutes to heart rate (mean) lowered by 10% from baseline after administration of study drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with heart rate <60 beats per minute | From adminstration of study drug to start af cardiac computed tomography, 2 hours | — |
| Total heart rate reduction in beats per minute after 120 minutes | From adminstration of study drug to start af cardiac computed tomography, 2 hours | — |
| Number of patients in need of an intravenous betablocker | From adminstration of study drug to start af cardiac computed tomography, 2 hours | Patients with a heart rate \>60 beats per minutes after 2 hours after administration of study drug |
| Efficacy of intravenous administration of betablocker | From adminstration of study drug to start af cardiac computed tomography, 2 hours | How patients tolerate intravenous betablocker |
| Evaluation of side effects, safety, and tolerability of metoprolol, atenolol, and ivabradine | From intervention af study drug to phone contact to patient 1 week after cardiac computed tomography | Phone contact to patient to describe any side effects and the tolerability |
Countries
Denmark
Outcome results
None listed