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

January 11, 2016 updated by: Radboud University Medical Center

The Effect of Eplerenone on Ischemia Reperfusion Injury in Human Myocardium (EPLICARD Study)

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6500HB
        • Radboud University Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Inspra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
210 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Investigators

  • Principal Investigator: Niels P. Riksen, Dr, Radboud University Medical Center
  • Principal Investigator: Henri A. van Swieten, Prof dr ir, Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

March 14, 2014

First Submitted That Met QC Criteria

April 16, 2014

First Posted (Estimate)

April 21, 2014

Study Record Updates

Last Update Posted (Estimate)

January 12, 2016

Last Update Submitted That Met QC Criteria

January 11, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EPLICARD

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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