Study of the Use of a Single Dose of Erythropoietin to Treat Acute Myocardial Ischemia (DREAM)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Willem-Peter Theodoor Ruifrok, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT00524901
First received: September 4, 2007
Last updated: February 13, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
CABG
Coronary Artery Disease
Drug: Epoetin alpha
Drug: NaCl 0.9%
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Difference between EPO- and saline treated subjects in TUNEL and active caspase-3 positive cells in ventricular and atrial biopsies. [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
  • Difference in AUC for CK-MB, Troponin T, NT-proBNP, and cystatin C between EPO- and saline treated patients. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Subject incidence rates of adverse events. [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: September 2007
Study Completion Date: April 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
25 patients undergoing CABG for three vessel disease, receiving a single dose of erythropoietin periprocedural.
Drug: Epoetin alpha
A single dose of epoetin alpha during CABG for three vessel disease, 60.000 IU intravenously.
Other Name: Eprex
Placebo Comparator: 2
25 patients undergoing CABG for three vessel disease, receiving placebo (NaCl 0.9%) periprocedural.
Drug: NaCl 0.9%
A single dose of NaCl 0.9% during CABG for three vessel disease, 1 ml intravenously.
Other Name: Saline

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00524901

Locations
Netherlands
University Medical Center Groningen, Dept. of Cardiology
Groningen, Netherlands, 9700 BD
Sponsors and Collaborators
University Medical Centre Groningen
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
  More Information

Additional Information:
No publications provided

Responsible Party: Willem-Peter Theodoor Ruifrok, MD, PhD, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT00524901     History of Changes
Other Study ID Numbers: WTR-ECG-2
Study First Received: September 4, 2007
Last Updated: February 13, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by University Medical Centre Groningen:
Apoptosis
CABG
Coronary Artery Disease
Three Vessel Disease
Erythropoietin
EPO-receptor signaling

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Epoetin alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014