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Trial record 3 of 112 for:    EPLERENONE

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

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ClinicalTrials.gov Identifier: NCT02118753
Recruitment Status : Completed
First Posted : April 21, 2014
Last Update Posted : January 12, 2016
Sponsor:
Information provided by (Responsible Party):
Radboud University

Tracking Information
First Submitted Date  ICMJE March 14, 2014
First Posted Date  ICMJE April 21, 2014
Last Update Posted Date January 12, 2016
Study Start Date  ICMJE March 2014
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 23, 2015)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 16, 2014)
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 forse 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.
Change History Complete list of historical versions of study NCT02118753 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2014)
contractile function in response to eplerenone vs eplerenone and caffeine [ Time Frame: 210 minutes ]
The recovery of contractile force (% of baseline) in human myocardial tissue by eplerenone with and without caffeine. If eplerenone indeed improves the recovery of contractile force in human myocardial tissue, then the investigators will co-administer caffeine to the organ bath to investigate whether the protective effect of eplerenone depends on adenosine receptor stimulation. The two trabeculae will be dissected and vertically suspended in an organ bath and linked to a forse 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: April 16, 2014)
contractile function in human atrial trabeculae in response to aldsterone [ Time Frame: 210 minutes ]
The recovery of contractile function (% of baseline) after ischemia and reperfusion in human myocardial tissue (2 trabeculae), after the addition of aldosterone to the organ bath (2 different concentrations) The two trabeculae will be dissected and vertically suspended in an organ bath and linked to a forse 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.
 
Descriptive Information
Brief Title  ICMJE The Effect of EPLerenone on Ischemia Reperfusion Injury in Human myoCARDium
Official Title  ICMJE The Effect of Eplerenone on Ischemia Reperfusion Injury in Human Myocardium (EPLICARD Study)
Brief Summary In the laboratory, the researchers will investigate whether the drug eplerenone improves contractile function after ischemia and reperfusion in heart tissue.
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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ischemia-reperfusion Injury
Intervention  ICMJE Drug: Eplerenone
eplerenone administered ex vivo (to the organ bath in which human atrial tissue is exposed)
Other Name: Inspra
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Eplerenone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 11, 2016)
24
Original Estimated Enrollment  ICMJE
 (submitted: April 16, 2014)
60
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02118753
Other Study ID Numbers  ICMJE EPLICARD
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Radboud University
Study Sponsor  ICMJE Radboud University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Niels P. Riksen, Dr Radboud University
Principal Investigator: Henri A. van Swieten, Prof dr ir Radboud University
PRS Account Radboud University
Verification Date January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP