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

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

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.

Study Overview

• Status: Unknown
• Conditions: Cardiogenic Shock
• Intervention / Treatment: Drug: Ivabradine Oral Tablet; Other: Standard of Care treatment

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital Universitario Ramon y Cajal
• Investigators: Principal Investigator: Marcelo Sanmartín Fernández, PhD, Hospital Universitario Ramon y Cajal

Publications and helpful links

General Publications

• Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K; INITIATIVE Investigators. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J. 2005 Dec;26(23):2529-36. doi: 10.1093/eurheartj/ehi586. Epub 2005 Oct 7.
• Swedberg K, Komajda M, Bohm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L; SHIFT Investigators. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010 Sep 11;376(9744):875-85. doi: 10.1016/S0140-6736(10)61198-1. Erratum In: Lancet. 2010 Dec 11;376(9757):1988. Lajnscak, M [corrected to Lainscak, M]; Rabanedo, I Roldan [corrected to Rabadan, I Roldan]; Leva, M [corrected to Ieva, M].
• Fasullo S, Cannizzaro S, Maringhini G, Ganci F, Giambanco F, Vitale G, Pinto V, Migliore G, Torres D, Sarullo FM, Paterna S, Di Pasquale P. Comparison of ivabradine versus metoprolol in early phases of reperfused anterior myocardial infarction with impaired left ventricular function: preliminary findings. J Card Fail. 2009 Dec;15(10):856-63. doi: 10.1016/j.cardfail.2009.05.013. Epub 2009 Jul 3.
• Lechat P, Hulot JS, Escolano S, Mallet A, Leizorovicz A, Werhlen-Grandjean M, Pochmalicki G, Dargie H. Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II Trial. Circulation. 2001 Mar 13;103(10):1428-33. doi: 10.1161/01.cir.103.10.1428.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2018
• Primary Completion (ANTICIPATED): October 1, 2019
• Study Completion (ANTICIPATED): October 1, 2019

Study Registration Dates

• First Submitted: January 15, 2018
• First Submitted That Met QC Criteria: February 12, 2018
• First Posted (ACTUAL): February 19, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 19, 2018
• Last Update Submitted That Met QC Criteria: February 12, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Ivabradine, heart rate, acute heart failure
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Shock; Shock, Cardiogenic
• Other Study ID Numbers: HURamonyCajal

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes