Clinical trial NCT03437369: Efficacy and Safety on Heart Rate Control With Ivabradine on Cardiogenic Shock
Official title: Efficacy and Safety on Heart Rate Control With Ivabradine on Cardiogenic Shock (ES-FISH)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Cardiogenic Shock
Keywords: Ivabradine, heart rate, acute heart failure
Lead sponsor: Hospital Universitario Ramon y Cajal
Sponsor class: OTHER
First posted: 2018-02-19
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Changes from baseline in pulmonary wedge pressure and cardiac output after 24h-treatment with ivabradine or standard of care treatment.
timeFrame: 24 hours
Secondary outcomes:
measure: Severe bradycardia
timeFrame: 24 hours
measure: Arrhythmias
timeFrame: 24 hours
measure: Hypotension
timeFrame: 24 hours
measure: Time to withdrawal of vasoactive drugs
timeFrame: 30 days
measure: Time needing invasive mechanical ventilation
timeFrame: 30 days
measure: B-type natriuretic peptide (BNP)
timeFrame: 30 days
measure: Left ventricular ejection fraction
timeFrame: 30 days
measure: Cardiovascular mortality
timeFrame: 30 days
measure: Total mortality
timeFrame: 30 days
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
Study officials:
affiliation: Hospital Universitario Ramon y Cajal
name: Marcelo Sanmartín Fernández, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1093/eurheartj/ehi586. Epub 2005 Oct 7.
citation: 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.
citation: 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.
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. doi: 10.1161/01.cir.103.10.1428.