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

• ClinicalTrials.gov Identifier: NCT03437369
• Recruitment Status: Unknown
• First Posted: February 19, 2018
• Last Update Posted: February 19, 2018
• Sponsor: Hospital Universitario Ramon y Cajal
• Information provided by (Responsible Party): Marcelo Sanmartín Fernández, Hospital Universitario Ramon y Cajal

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cardiogenic Shock	Drug: Ivabradine Oral Tablet; Other: Standard of Care treatment	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety on Heart Rate Control With Ivabradine on Cardiogenic Shock (ES-FISH)
• Estimated Study Start Date: May 2018
• Estimated Primary Completion Date: October 2019
• Estimated Study Completion Date: October 2019

Arms and Interventions

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
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

Outcome Measures

Primary Outcome Measures :

1. Changes from baseline in pulmonary wedge pressure and cardiac output after 24h-treatment with ivabradine or standard of care treatment. [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Marcelo Sanmartín Fernández, PhD; +34 91 336 80 00; msanfer@me.com

Locations

Spain

Hospital Universitario Ramón y Cajal

Madrid, Spain, 28034

Contact: Marcelo Sanmartin, MD +34 91 336 80 00 msanfer@me.com

Sub-Investigator: Marina Pascual Izco, MD

Sub-Investigator: Luis Miguel Rincón Díaz, MD

Sub-Investigator: Gonzalo Luis Alonso Salinas, MD

Sub-Investigator: Manuel Jimenez Mena, MD

Sub-Investigator: Asunción Camino González, MD

Sub-Investigator: Jose Luis Zamorano, MD

Principal Investigator: Marcelo Sanmartín Fernandez, MD

Sponsors and Collaborators

Hospital Universitario Ramon y Cajal

Investigators

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

More Information

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. Epub 2005 Oct 7.

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].

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.

• Responsible Party: Marcelo Sanmartín Fernández, Director Acute Coronary Syndrome Process, Hospital Universitario Ramon y Cajal
• ClinicalTrials.gov Identifier: NCT03437369
• Other Study ID Numbers: HURamonyCajal
• First Posted: February 19, 2018
• Last Update Posted: February 19, 2018
• Last Verified: February 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Marcelo Sanmartín Fernández, Hospital Universitario Ramon y Cajal:

Ivabradine, heart rate, acute heart failure

Additional relevant MeSH terms:

Shock, Cardiogenic; Shock; Pathologic Processes; Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Necrosis