Ischemia-reperfusion InjuryEPLICARDNCT02118753
The Effect of EPLerenone on Ischemia Reperfusion Injury in Human myoCARDium
A study testing Eplerenone in people with Ischemia-reperfusion Injury, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
In the laboratory, the researchers will investigate whether the drug eplerenone improves contractile function after ischemia and reperfusion in heart tissue. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemia-reperfusion Injury
- What is being tested?
- Eplerenone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2014to Jan 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age>18 years
- willing to sign informed consent
- planned elective surgery with extracorporal circulation
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Medical Centre
Nijmegen, Gelderland, 6500HB
About this study
Official title: 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.
Read the 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.
- Conditions
- Ischemia-reperfusion Injury
- Being tested
- Eplerenone
- Keywords
- ischemia-reperfusion injury
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EplerenoneDrug
Also called Inspra
eplerenone administered ex vivo (to the organ bath in which human atrial tissue is exposed)
| Study group | Role | What they receive |
|---|---|---|
| ischemic preconditioning | No intervention | 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. |
| eplerenone | Experimental | 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. Receives: Drug: Eplerenone |
What is being measured
The primary outcome is the main question the study is designed to answer.
contractile function after simulated ischemia and reperfusion in response to eplerenone
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.
Measured: 210 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2014 (estimated)
- Study startMar 2014
- Primary completionDec 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ischemia-reperfusion InjuryStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Niels P. Riksen, Dr, Principal investigator, Radboud University Medical CenterHenri A. van Swieten, Prof dr ir, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02118753
- Sponsor's protocol ID
- EPLICARD
- Acronym
- EPLICARD
- Status last verified
- Jan 2016
- First submitted
- 14 Mar 2014
- Last updated
- 12 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Riksen NP, Zhou Z, Oyen WJ, Jaspers R, Ramakers BP, Brouwer RM, Boerman OC, Steinmetz N, Smits P, Rongen GA. Caffeine prevents protection in two human models of ischemic preconditioning. J Am Coll Cardiol. 2006 Aug 15;48(4):700-7. doi: 10.1016/j.jacc.2006.04.083. Epub 2006 Jul 24.
PubMed 16904537Speechly-Dick ME, Grover GJ, Yellon DM. Does ischemic preconditioning in the human involve protein kinase C and the ATP-dependent K+ channel? Studies of contractile function after simulated ischemia in an atrial in vitro model. Circ Res. 1995 Nov;77(5):1030-5. doi: 10.1161/01.res.77.5.1030.
PubMed 7554138
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Eplerenone on Ischemia Reperfusion Injury in Human Myocardium (EPLICARD Study)
- ClinicalTrials.gov ID
- NCT02118753
- Acronym / sponsor ID
- EPLICARD / EPLICARD
- Conditions
- Ischemia-reperfusion Injury
- Keywords
- ischemia-reperfusion injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 21 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ischemic preconditioning | No intervention | –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. |
| eplerenone | Experimental | Drug: EplerenoneIn 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- age>18 years
- willing to sign informed consent
- planned elective surgery with extracorporal circulation
Key exclusion criteria (7 listed)
- use of theophylline
- use of sulfonylureas
- use of oral antiarrhythmics (not beta blockers)
- use of dipyridamole, use of mineralocorticoid receptor antagonists
- atrial arrhythmias
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EplerenoneAlso: Inspraeplerenone administered ex vivo (to the organ bath in which human atrial tissue is exposed) | Drug | eplerenone |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2016.
- Background: PubMed 16904537Riksen NP, Zhou Z, Oyen WJ, Jaspers R, Ramakers BP, Brouwer RM, Boerman OC, Steinmetz N, Smits P, Rongen GA. Caffeine prevents protection in two human models of ischemic preconditioning. J Am Coll Cardiol. 2006 Aug 15;48(4):700-7. doi: 10.1016/j.jacc.2006.04.083. Epub 2006 Jul 24.
- Background: PubMed 7554138Speechly-Dick ME, Grover GJ, Yellon DM. Does ischemic preconditioning in the human involve protein kinase C and the ATP-dependent K+ channel? Studies of contractile function after simulated ischemia in an atrial in vitro model. Circ Res. 1995 Nov;77(5):1030-5. doi: 10.1161/01.res.77.5.1030.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Niels P. Riksen, Dr principal investigator
Radboud University Medical Center
Henri A. van Swieten, Prof dr ir principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Eplerenone in people with Ischemia-reperfusion Injury, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
contractile function after simulated ischemia and reperfusion in response to eplerenone (time frame: 210 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02118753, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2016; AzTrials last refreshed its copy on 8 Nov 2026.