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

Cardiogenic Shock Clinical Trial

— ES-FISH  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03437369
• Other study ID #: HURamonyCajal
• Status: Not yet recruiting
• Phase: Phase 4
• First received: January 15, 2018
• Last updated: February 12, 2018
• Start date: May 2018
• Est. completion date: October 2019

Study information

• Verified date: February 2018
• Source: Hospital Universitario Ramon y Cajal
• Contact: Marcelo Sanmartín Fernández, PhD
• Phone: +34 91 336 80 00
• Email: msanfer[@]me.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 22
• Est. completion date: October 2019
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiogenic Shock
• Shock
• Shock, Cardiogenic

Intervention

Drug:
• Ivabradine Oral Tablet
The target dose is 10 to 15 mg / day, administered orally in two doses

Other:
• Standard of Care treatment
The study drug will be compared with the standard of Care treatment

Locations

Country	Name	City	State
Spain	Hospital Universitario Ramón y Cajal	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario Ramon y Cajal

Country where clinical trial is conducted

Spain, 

References & Publications (4)

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. — View Citation

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. — View Citation

Swedberg K, Komajda M, Böhm 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 Rabadán, I Roldan]; Leva, M [corrected to Ieva, M]. — View Citation

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. Epub 2005 Oct 7. — View Citation

Outcome

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