CABGPhase 2DREAMNCT00524901
Study of the Use of a Single Dose of Erythropoietin to Treat Acute Myocardial Ischemia
A Phase 2 study testing Epoetin alpha and NaCl 0.9% in people with CABG and Coronary Artery Disease, run by University Medical Center Groningen at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- CABG, Coronary Artery Disease
- What is being tested?
- Epoetin alpha and NaCl 0.9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2007to Apr 2011
- Phase
- Phase 2
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
University Medical Center Groningen, Dept. of Cardiology
Groningen, Provincie Groningen, 9700 BD
About this study
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
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.
- Conditions
- CABG, Coronary Artery Disease
- Being tested
- Epoetin alpha, NaCl 0.9%
- Keywords
- Apoptosis, CABG, Coronary Artery Disease, Three Vessel Disease, Erythropoietin, EPO-receptor signaling
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epoetin alphaDrug
Also called Eprex
A single dose of epoetin alpha during CABG for three vessel disease, 60.000 IU intravenously.
NaCl 0.9%Drug
Also called Saline
A single dose of NaCl 0.9% during CABG for three vessel disease, 1 ml intravenously.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 25 patients undergoing CABG for three vessel disease, receiving a single dose of erythropoietin periprocedural. Receives: Drug: Epoetin alpha |
| 2 | Placebo comparator | 25 patients undergoing CABG for three vessel disease, receiving placebo (NaCl 0.9%) periprocedural. Receives: Drug: NaCl 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 hours
Secondary outcomes (4)
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.
Measured: 2 hours
Difference between EPO- and saline treated subjects in TUNEL and active caspase-3 positive cells in ventricular and atrial biopsies.
Measured: 2 hours
Difference in AUC for CK-MB, Troponin T, NT-proBNP, and cystatin C between EPO- and saline treated patients.
Measured: 30 days
Subject incidence rates of adverse events.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2007 (estimated)
- Study startSep 2007
- Primary completionJan 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CABGStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Willem-Peter Theodoor Ruifrok, University Medical Center Groningen
- Investigators
- W. H. van Gilst, Prof, dr, Study chair, University Medical Center Groningen, Dept. of Exprimental CardiologyW. T. Ruifrok, MD, Principal investigator, University Medical Center Groningen, Dept. of Experimental CardiologyB. D. Westenbrink, MD, Principal investigator, University Medical Center Groningen, Dept. of Experimental CardiologyA. H. Epema, dr, MD, Principal investigator, University Medical Center Groningen, Dept. of AnaesthesiologyH. E. Mungroop, dr, MD, Principal investigator, University Medical Center Groningen, Dept. of AnaesthesiologyP. W. Boonstra, Prof, dr, MD, Principal investigator, University Medical Center Groningen, Dept. of Cardiothoracic SurgeryR. A. de Boer, dr, MD, Principal investigator, University Medical Center Groningen, Dept of CardiologyD. J. van Veldhuisen, Prof, dr, MD, Study director, University Medical Center Groningen, Dept. of Cardiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00524901
- Sponsor's protocol ID
- WTR-ECG-2
- Acronym
- DREAM
- Status last verified
- Feb 2013
- First submitted
- 4 Sep 2007
- Last updated
- 15 Feb 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00524901
- Acronym / sponsor ID
- DREAM / WTR-ECG-2
- Conditions
- CABG, Coronary Artery Disease
- Keywords
- Apoptosis, CABG, Coronary Artery Disease, Three Vessel Disease, Erythropoietin, EPO-receptor signaling
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Study start
- Sep 2007
- Primary completion
- Jan 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 5 Sep 2007 (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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Epoetin alpha25 patients undergoing CABG for three vessel disease, receiving a single dose of erythropoietin periprocedural. |
| 2 | Placebo comparator | Drug: NaCl 0.9%25 patients undergoing CABG for three vessel disease, receiving placebo (NaCl 0.9%) periprocedural. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
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 |
|---|---|---|
| Epoetin alphaAlso: EprexA single dose of epoetin alpha during CABG for three vessel disease, 60.000 IU intravenously. | Drug | 1 |
| NaCl 0.9%Also: SalineA single dose of NaCl 0.9% during CABG for three vessel disease, 1 ml intravenously. | Drug | 2 |
Primary outcome
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
4 secondary outcomes
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
Difference between EPO- and saline treated subjects in TUNEL and active caspase-3 positive cells in ventricular and atrial biopsies.
Time frame: 2 hours
Difference in AUC for CK-MB, Troponin T, NT-proBNP, and cystatin C between EPO- and saline treated patients.
Time frame: 30 days
Subject incidence rates of adverse events.
Time frame: 30 days
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 15 Feb 2013.
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Coronary Artery Bypass Graft (CABG)
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.
W. H. van Gilst, Prof, dr study chair
University Medical Center Groningen, Dept. of Exprimental Cardiology
W. T. Ruifrok, MD principal investigator
University Medical Center Groningen, Dept. of Experimental Cardiology
B. D. Westenbrink, MD principal investigator
University Medical Center Groningen, Dept. of Experimental Cardiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Epoetin alpha and NaCl 0.9% in people with CABG and Coronary Artery Disease, run by University Medical Center Groningen 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 4 inclusion and 16 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 15 Feb 2013. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Feb 2013.