- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00524901
Study of the Use of a Single Dose of Erythropoietin to Treat Acute Myocardial Ischemia (DREAM)
February 13, 2013 updated by: Willem-Peter Theodoor Ruifrok, University Medical Center Groningen
An Open Label Study to Evaluate the Effect of Intravenous Erythropoietin on Erythropoietin Receptor Signaling and Markers for Apoptosis, Myocardial Damage and Renal Dysfunction in Patients Undergoing Coronary Artery Bypass Graft (CABG) Surgery
This is a phase 2 study that evaluates the effect of intravenous administration of a bolus EPO on the activation of EPOR-signal transduction cascades and myocardial apoptosis during cardiopulmonary bypass surgery.
Human atrial and ventricular tissue will be collected during CABG surgery for 3-vessel disease for the assay of EPOR signaling and apoptosis.
Two atrial specimens will be collected before and at the end of cardiopulmonary bypass (CPB).
Concomitantly, two transmural ventricular biopsies will be obtained, at the start and at the end of CPB.
Immediately after obtaining the first atrial biopsy, one bolus of EPO will be administered intravenously.
The atrial tissue will be split and appropriate sections will be frozen for determination of baseline expression or activity of a number of molecules including Erk1/2, STAT5, Akt and caspase-3 or embedded in paraffin for immunohistochemistry. Ventricular tissue will only be processed for immunohistochemistry. Additionally, plasma will be collected before the procedure and for up to 30 days post-procedure to examine release of markers of both myocardial ischemia and stress (CK-MB, Troponin T and NT-proBNP) and renal dysfunction (cystatin C, creatinine for eGFR).
Before initializing the randomised study, a pilot study will be performed with 5 subjects that will not be treated to evaluate the feasibility of myocardial sample collection.
Initiation of the randomised study will only commence if baseline activity of EPOR-STC can be determined in the atrial tissue and caspase-3 positive cells can be identified in the second ventricular biopsy.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
10
Phase
- Phase 2
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
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Groningen, Netherlands, 9700 BD
- University Medical Center Groningen, Dept. of Cardiology
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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 to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Before any study-specific procedure, including assessments for screening, the appropriate written informed consent must be obtained.
- Man or woman 18 to 80 years of age .
- Undergoing a planned, elective cardiopulmonary bypass operation for the first time for 3-vessel coronary artery disease with an anticipated aortic cross clamp time of approximately 40 minutes and a total bypass time of approximately 90 minutes.
- Hemoglobin (Hb) concentration ≥7.4 mmol/l and ≤9.9 mmol/l within 7 days prior to CABG surgery and no major acute blood loss since this Hb determination.
Exclusion Criteria:
- An unstable medical condition, defined as having been hospitalized for a non-cardiac condition within 4 weeks of screening, major surgery within 24 weeks of screening, or otherwise unstable in the judgment of the investigator (e.g., at risk of complications or adverse events unrelated to study participation).
- Left ventricular ejection fraction (LVEF) < 40%.
- Clinical history of chronic kidney disease (CKD) (at any point prior to registration) defined as serum creatinine >105 μmol/l for all females, >130 μmol/l for black males, and >115 μmol/l for non-black males.
- Atrial fibrillation, paroxysmal atrial fibrillation or atrial flutter.
- Clinically significant abnormality in chemistry, hematology, or urinalysis parameters performed within the screening period.
- Current symptoms of polyurea, polydipsia, or increased thirst.
- Grand mal seizure within 1 year of enrollment.
- Poorly controlled hypertension, defined as systolic blood pressure (SBP) > 180 mmHg or diastolic blood pressure (DBP) > 105 mmHg on day of CABG surgery.
- Use of any erythropoietic protein (e.g., rHuEPO; Procrit®, Eprex®, Neorecormon®, Epogen®, Aranesp®) within 12 weeks of enrolment.
- Positive pregnancy test or known to be pregnant at the time of screening.
- Recent (within 3 months) history of alcohol or illicit drug abuse disorder, based on self-report.
- Severe uncorrected valvular disease (including pulmonary and tricuspid) or left ventricular outflow obstruction which, in the opinion of the investigator, requires surgery.
- Pulmonary hypertension, defined as a pulmonary artery pressure > 30 mmHg at rest.
- Participation in any investigational device or drug trial(s) or receiving other investigational agent(s) within 30 days.
- Known positive for HIV antibodies, hepatitis B surface antigen, or hepatitis C antibodies.
- Any condition (e.g., unsuitable anatomy of the atrium; psychiatric illness; etc.) or situation that, in the investigator's opinion, could put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study.
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: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
25 patients undergoing CABG for three vessel disease, receiving a single dose of erythropoietin periprocedural.
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A single dose of epoetin alpha during CABG for three vessel disease, 60.000 IU intravenously.
Other Names:
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Placebo Comparator: 2
25 patients undergoing CABG for three vessel disease, receiving placebo (NaCl 0.9%) periprocedural.
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A single dose of NaCl 0.9% during CABG for three vessel disease, 1 ml intravenously.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The increase from baseline between EPO and saline treated subjects in activity of EPOR-STC including but not limited to, phospho Erk1/2, phospho Akt, activated caspase-3, and activated STAT5 in the second atrial biopsy.
Time Frame: 2 hours
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2 hours
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Difference in apoptosis between atrial and ventricular specimens at the end of CPB, defined as the number of TUNEL and activated caspase-3 positive cells per high power field.
Time Frame: 2 hours
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2 hours
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Difference between EPO- and saline treated subjects in TUNEL and active caspase-3 positive cells in ventricular and atrial biopsies.
Time Frame: 2 hours
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2 hours
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Difference in AUC for CK-MB, Troponin T, NT-proBNP, and cystatin C between EPO- and saline treated patients.
Time Frame: 30 days
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30 days
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Subject incidence rates of adverse events.
Time Frame: 30 days
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30 days
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Chair: W. H. van Gilst, Prof, dr, University Medical Center Groningen, Dept. of Exprimental Cardiology
- Principal Investigator: W. T. Ruifrok, MD, University Medical Center Groningen, Dept. of Experimental Cardiology
- Principal Investigator: B. D. Westenbrink, MD, University Medical Center Groningen, Dept. of Experimental Cardiology
- Principal Investigator: A. H. Epema, dr, MD, University Medical Center Groningen, Dept. of Anaesthesiology
- Principal Investigator: H. E. Mungroop, dr, MD, University Medical Center Groningen, Dept. of Anaesthesiology
- Principal Investigator: P. W. Boonstra, Prof, dr, MD, University Medical Center Groningen, Dept. of Cardiothoracic Surgery
- Principal Investigator: R. A. de Boer, dr, MD, University Medical Center Groningen, Dept of Cardiology
- Study Director: D. J. van Veldhuisen, Prof, dr, MD, University Medical Center Groningen, Dept. of Cardiology
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.
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
September 1, 2007
Primary Completion (Actual)
January 1, 2011
Study Completion (Actual)
April 1, 2011
Study Registration Dates
First Submitted
September 4, 2007
First Submitted That Met QC Criteria
September 4, 2007
First Posted (Estimate)
September 5, 2007
Study Record Updates
Last Update Posted (Estimate)
February 15, 2013
Last Update Submitted That Met QC Criteria
February 13, 2013
Last Verified
February 1, 2013
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- WTR-ECG-2
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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