Levosimendan Versus Dobutamine for Renal Function in Heart Failure (ELDOR)

• ClinicalTrials.gov Identifier: NCT02133105
• Recruitment Status: Completed
• First Posted: May 7, 2014
• Last Update Posted: February 25, 2020
• Sponsor: Göteborg University
• Collaborator: Sahlgrenska University Hospital, Sweden
• Information provided by (Responsible Party): Göteborg University

Study Description

Brief Summary:

Although inotropes have a favorable effect on central hemodynamics in patients with heart failure, their effect on renal hemodynamics is incompletely defined. The purpose of this study is to evaluate the efficacy of a 75 min intravenous infusion of levosimendan compared to a 75 min infusion of dobutamine on renal hemodynamics and function in patients with chronic heart failure and signs of cardiorenal syndrome. The investigators hypothesis is that patients treated with levosimendan will show greater increases in renal blood flow and glomerular filtration rate (GFR) than those treated with dobutamine.

Condition or disease	Intervention/treatment	Phase
Cardiorenal Syndrome	Drug: Levosimendan; Drug: Dobutamine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy of Intravenous Levosimendan Compared With Dobutamine on Renal Hemodynamics and Function in Chronic Heart Failure
• Actual Study Start Date: April 2014
• Actual Primary Completion Date: May 2017
• Actual Study Completion Date: May 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Levosimendan; Levosimendan administration is initiated with a loading dose of 12μg/kg given over 10 min followed by a continuous infusion of 0.1 μg/kg/min for 65 min.	Drug: Levosimendan; Other Name: Simdax
Active Comparator: Dobutamine; Dobutamine is given as a continuous infusion without a bolus dose. The infusion rate is started at 5.0 μg/kg/min for 10 minutes, and thereafter increased to 7,5 μg/kg/min for 65 min.	Drug: Dobutamine; Other Name: Dobutrex

Outcome Measures

Primary Outcome Measures :

1. Change in renal blood flow [ Time Frame: 75 min minus baseline ]
   Para-aminohippuric acid (PAH) infusion clearance
2. Change in glomerular filtration rate [ Time Frame: 75 min minus baseline ]
   Chrome-ethylenediaminetetraacetic acid (EDTA) infusion clearance

Secondary Outcome Measures :

1. Change in renal vascular resistance [ Time Frame: 75 min minus baseline ]
   Renal blood flow divided by the difference between renal arterial pressure and renal venous pressure
2. Change in central hemodynamics [ Time Frame: 75 min minus baseline ]
   Right atrial pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, mean arterial pressure, cardiac output, pulmonary vascular resistance and systemic vascular resistance measured with a pulmonary artery thermodilution catheter.
3. Change in renal oxygen consumption and oxygen extraction [ Time Frame: 75 min minus baseline ]

   Oxygen consumption: Renal blood flow multiplied by arterial-renal venous oxygen difference.

   Oxygen extraction: Ratio of renal oxygen consumption to renal oxygen delivery

4. Change in filtration fraction [ Time Frame: 75 min minus baseline ]
   Ratio of glomerular filtration rate to renal plasma flow

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:

• Written, signed and dated informed consent
• Male and Female subjects ≥18 years of age
• Chronic congestive heart failure scheduled for right sided cardiac catheterization
• Left ventricular ejection fraction ≤ 40% determined by echocardiography
• Elevation of N Terminal-proBNP ≥ 500 ng/L
• Cardiorenal syndrome (30ml/min ≤ estimated GFR ≤ 80 ml/min (MDRD)

Exclusion Criteria:

• Acute heart failure, untreated
• Systolic blood pressure < 80 mmHg
• Tachycardia above 100 bpm
• Angina Canadian Cardiovascular Society (CCS) class III or higher
• Aortic stenosis
• Hypertrophic cardiomyopathy
• Restrictive cardiomyopathy
• The presence of kidney disease diagnosed before heart failure
• Administration of radiographic contrast < 1 week
• Radiographic contrast allergy
• In the Investigator's opinion, the patient has a clinically significant disease that could be adversely affected by study participation

Contacts and Locations

Locations

Sweden

Sahlgrenska University Hospital

Gothenburg, Sweden, 41345

Sponsors and Collaborators

Göteborg University

Sahlgrenska University Hospital, Sweden

Investigators

• Principal Investigator: Kristjan Karason, MD, PhD; Sahlgrenska University Hospital, Department of Cardiology

More Information

Publications of Results:

Savarese G, Lund LH. Global Public Health Burden of Heart Failure. Card Fail Rev. 2017 Apr;3(1):7-11. doi: 10.15420/cfr.2016:25:2.

Hillege HL, Nitsch D, Pfeffer MA, Swedberg K, McMurray JJ, Yusuf S, Granger CB, Michelson EL, Ostergren J, Cornel JH, de Zeeuw D, Pocock S, van Veldhuisen DJ; Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Investigators. Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation. 2006 Feb 7;113(5):671-8.

Smith GL, Shlipak MG, Havranek EP, Masoudi FA, McClellan WM, Foody JM, Rathore SS, Krumholz HM. Race and renal impairment in heart failure: mortality in blacks versus whites. Circulation. 2005 Mar 15;111(10):1270-7.

Hillege HL, Girbes AR, de Kam PJ, Boomsma F, de Zeeuw D, Charlesworth A, Hampton JR, van Veldhuisen DJ. Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation. 2000 Jul 11;102(2):203-10.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lannemyr L, Ricksten SE, Rundqvist B, Andersson B, Bartfay SE, Ljungman C, Dahlberg P, Bergh N, Hjalmarsson C, Gilljam T, Bollano E, Karason K. Differential Effects of Levosimendan and Dobutamine on Glomerular Filtration Rate in Patients With Heart Failure and Renal Impairment:A Randomized Double-Blind Controlled Trial. J Am Heart Assoc. 2018 Aug 21;7(16):e008455. doi: 10.1161/JAHA.117.008455.

• Responsible Party: Göteborg University
• ClinicalTrials.gov Identifier: NCT02133105
• Other Study ID Numbers: 2013-000986-36; 2013-000986-36 ( EudraCT Number )
• First Posted: May 7, 2014
• Last Update Posted: February 25, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Keywords provided by Göteborg University:

Heart failure; Renal failure; Inotropic drugs; Levosimendan; Dobutamine

Additional relevant MeSH terms:

Cardio-Renal Syndrome; Heart Failure; Heart Diseases; Cardiovascular Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Simendan; Dobutamine; Cardiotonic Agents; Vasodilator Agents; Phosphodiesterase 3 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Sympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic beta-1 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents