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The Effect of EPLerenone on Ischemia Reperfusion Injury in Human myoCARDium (EPLICARD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02118753
Recruitment Status : Completed
First Posted : April 21, 2014
Last Update Posted : January 12, 2016
Information provided by (Responsible Party):
Radboud University

Brief Summary:
In the laboratory, the researchers will investigate whether the drug eplerenone improves contractile function after ischemia and reperfusion in heart tissue.

Condition or disease Intervention/treatment Phase
Ischemia-reperfusion Injury Drug: Eplerenone Not Applicable

Detailed Description:

In animal studies, the mineralocorticoid receptor antagonist eplerenone appears to limit myocardial infarct size. This cardioprotective effect might explain, at least in part, the beneficial effect on mortality of eplerenone in patients with heart failure. Previous animal studies suggest that this cardioprotective effect is mediated by an increased formation of the endogenous nucleoside adenosine.

Our objective is to study for the first time in human myocardial tissue ex vivo wether eplerenone limits ischemia reperfusion injury and whether this is mediated by adenosine receptor stimulation.

From patients undergoing open heart surgery, the right atrial appendage will be harvested by the cardiothoracic surgeon. In the laboratory, two trabeculae will be dissected and suspended in an organ bath. Contraction will be induced by electrical field stimulation. Recovery of contractile force after a period of simulated ischemia and reperfusion will be used as an endpoint of ischemia-reperfusion injury.

The trabeculae of each patient will be randomized to pretreatment with A)ischemic preconditioning (IP) of no IP as a positive control experiment; B)eplerenone or vehicle; C)eplerenone with or without caffeine; and D)aldosterone with and without eplerenone.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Eplerenone on Ischemia Reperfusion Injury in Human Myocardium (EPLICARD Study)
Study Start Date : March 2014
Actual Primary Completion Date : December 2015
Actual Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Eplerenone

Arm Intervention/treatment
No Intervention: ischemic preconditioning

After baseline recordings of contractile function, the investigators will assign 2 trabeculae of each patient to either a stimulus for (1) ischemic preconditioning (IP) or (2) no IP. Subsequently, the trabeculae will be exposed to 90 min of ischemia, followed by 120 minutes of recovery. The investigators will measure the recovery of contractile function in both trabeculae.

This experiment serves as a positive control, to ensure that our model is still working properly.

Experimental: eplerenone
In the next patients, a similar ischemia-reperfusion experiment will be performed, but now the 2 trabeculae will be randomized to pretreatment with eplerenone or DMSO. The percentage recovery (compared to baseline) of contractile force of the trabeculae at the end of reperfusion will serve as the primary endpoint.
Drug: Eplerenone
eplerenone administered ex vivo (to the organ bath in which human atrial tissue is exposed)
Other Name: Inspra

Primary Outcome Measures :
  1. contractile function after simulated ischemia and reperfusion in response to eplerenone [ Time Frame: 210 minutes ]

    The recovery of contractile function (% of baseline) in human myocardial tissue after simulated ischemia and reperfusion in 2 trabeculae will be compared: 1 of the trabeculae will be exposed to eplerenone, the other to vehicle.

    We will use the experimental set up as described by Speechly-Dick et al. with small modifications to allow simultaneous measurement of 2 trabeculae from 1 patient. The two trabeculae will be dissected and vertically suspended in an organ bath and linked to a force transducer. During electrical field stimulation, we will calculate the developed force (difference between maximal tension during contraction and minimal tension during relaxation), maximal speed of tension development during contraction and maximal speed of tension during relaxation. We will average these parameters for baseline, and during the experiment. Functional recovery will be expressed as a percentage of baseline.

Information from the National Library of Medicine

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

Inclusion Criteria:

  • age>18 years
  • willing to sign informed consent
  • planned elective surgery with extracorporal circulation

Exclusion Criteria:

  • use of theophylline
  • use of sulfonylureas
  • use of oral antiarrhythmics (not beta blockers)
  • use of dipyridamole, use of mineralocorticoid receptor antagonists
  • atrial arrhythmias
  • right ventricular failure
  • known atrial enlargement

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02118753

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Radboud University Medical Centre
Nijmegen, Gelderland, Netherlands, 6500HB
Sponsors and Collaborators
Radboud University
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Principal Investigator: Niels P. Riksen, Dr Radboud University
Principal Investigator: Henri A. van Swieten, Prof dr ir Radboud University

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Responsible Party: Radboud University Identifier: NCT02118753    
Other Study ID Numbers: EPLICARD
First Posted: April 21, 2014    Key Record Dates
Last Update Posted: January 12, 2016
Last Verified: January 2016
Keywords provided by Radboud University:
ischemia-reperfusion injury
Additional relevant MeSH terms:
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Reperfusion Injury
Wounds and Injuries
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Natriuretic Agents
Antihypertensive Agents