Efficacy and Safety on Heart Rate Control With Ivabradine on Cardiogenic Shock

Study Overview
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Brief Summary
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This is a randomized 1:1 blinded study that evaluate in acute left heart failure-cardiogenic shock patients if ivabradine treatment can reduce pulmonary wedge pressure, without inducing a significant or relevant reduction in cardiac output or increasing the risk of arterial hypotension and with the benefit of allowing a faster titration of heart failure drugs.

Official Title
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Efficacy and Safety on Heart Rate Control With Ivabradine on Cardiogenic Shock (ES-FISH)

Conditions
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Cardiogenic Shock

Intervention / Treatment
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* Drug: Ivabradine Oral Tablet
* Other: Standard of Care treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 18 years, with acute heart failure due to left ventricular systolic dysfunction (LVEF ≤ 40%) in sinus rhythm, baseline HR ≥ 90 bpm, with signs of low peripheral perfusion with indication for intravenous inotropic treatment (catecholamines: dobutamine , adrenaline, dopamine or noradrenaline) and admitted to the Cardiological Intensive Care Unit. Pharmacological treatment and stable hemodynamic situation in the 4 hours before inclusion. Pulmonary wedge pressure ≥ 18 mm Hg and systolic blood pressure > 90 mm Hg. Patient's signature on the consent form. Exclusion Criteria: Previous treatment with ivabradine (< 48 hours). Known hypersensitivity to ivabradine. Cardiac rhythm different from sinus rhythm. Unstable cardiac rhythm due to paroxysmal atrial fibrillation or atrial flutter, very frequent ventricular or supraventricular premature beats, ventricular tachycardia, 2nd or 3rd degree atrioventricular (AV) block. Severe chronic renal failure (estimated glomerular filtration rate ≤15 ml / min) or on chronic treatment with dialysis. QT interval higher than 450 ms. Sepsis as a probable mechanism of tachycardia and hypotension. Need for urgent cardiac surgery, planned within 72 hours of possible inclusion. Severe aortic stenosis or severe valvular disease that requires surgical correction. Patient must not have received an IV bolus of furosemide immediately before the baseline hemodynamic assessment. Severe hepatic insufficiency. Patient must not be participating in another clinical trial. Concomitant use of potent CYP3A4 inhibitors. Acute anemia or hypovolemia uncorrected. Pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ivabradine<br>Drug: Ivabradine Oral tablets 2.5 mg Dose: 10-15 mg/day Duration: 30 days | Drug: Ivabradine Oral Tablet<br>* The target dose is 10 to 15 mg / day, administered orally in two doses<br>|
| Other: Standard of Care<br>The study drug will be compared with standard of Care treatment | Other: Standard of Care treatment<br>* The study drug will be compared with the standard of Care treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in pulmonary wedge pressure and cardiac output after 24h-treatment with ivabradine or standard of care treatment. | Reduction of pulmonary wedge pressure from baseline in both treatment arms (ivabradine arm versus standard of care treatment measured by Swan Ganz balloon flotation catheter) | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe bradycardia | -Development of excessive bradycardia defined as heart rate (HR) <50 beats per minute | 24 hours | 
| Arrhythmias | New-onset of ventricular arrhythmias or atrial fibrillation | 24 hours | 
| Hypotension | Hypotension, defined as systolic blood pressure <90 mmHg | 24 hours | 
| Time to withdrawal of vasoactive drugs | -Time to catecholamine withdrawal in both treatment arms (days) | 30 days | 
| Time needing invasive mechanical ventilation | Mechanical (invasive) ventilation time after initiation of ivabradine/control treatment. | 30 days | 
| B-type natriuretic peptide (BNP) | Measured B-type natriuretic peptide (BNP) values at 30 days | 30 days | 
| Left ventricular ejection fraction | Change in left ventricle ejection fraction from baseline in both treatment arms (%) | 30 days | 
| Cardiovascular mortality | Mortality due to cardiovascular causes | 30 days | 
| Total mortality | Mortality from any cause | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ivabradine, heart rate, acute heart failure