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

Phase 4

• Conditions: Cardiogenic Shock
• Interventions: Drug: Ivabradine Oral Tablet; Other: Standard of Care treatment

• Registration Number: NCT03437369
• Lead Sponsor: Hospital Universitario Ramon y Cajal

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-01-15
• Status Verified: 2018-02
• Study First Submitted QC: 2018-02-12
• Last Update Submitted: 2018-02-12
• Study First Posted: 2018-02-19
• Last Update Posted: 2018-02-19
• Study Start: 2018-05
• Primary Completion: 2019-10
• Study Completion: 2019-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 22

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ivabradine	Ivabradine Oral Tablet	Drug: Ivabradine Oral tablets 2.5 mg Dose: 10-15 mg/day Duration: 30 days
Standard of Care	Standard of Care treatment	The study drug will be compared with standard of Care treatment

Primary Outcome Measures

Name	Time	Method
Changes from baseline in pulmonary wedge pressure and cardiac output after 24h-treatment with ivabradine or standard of care treatment.	24 hours	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)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain