- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00524901
Study of the Use of a Single Dose of Erythropoietin to Treat Acute Myocardial Ischemia (DREAM)
13. februar 2013 oppdatert av: 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.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
10
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Groningen, Nederland, 9700 BD
- University Medical Center Groningen, Dept. of Cardiology
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 80 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: 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.
Andre navn:
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Placebo komparator: 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.
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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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.
Tidsramme: 2 hours
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2 hours
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Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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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.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 30 days
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30 days
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Subject incidence rates of adverse events.
Tidsramme: 30 days
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30 days
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Etterforskere
- Studiestol: W. H. van Gilst, Prof, dr, University Medical Center Groningen, Dept. of Exprimental Cardiology
- Hovedetterforsker: W. T. Ruifrok, MD, University Medical Center Groningen, Dept. of Experimental Cardiology
- Hovedetterforsker: B. D. Westenbrink, MD, University Medical Center Groningen, Dept. of Experimental Cardiology
- Hovedetterforsker: A. H. Epema, dr, MD, University Medical Center Groningen, Dept. of Anaesthesiology
- Hovedetterforsker: H. E. Mungroop, dr, MD, University Medical Center Groningen, Dept. of Anaesthesiology
- Hovedetterforsker: P. W. Boonstra, Prof, dr, MD, University Medical Center Groningen, Dept. of Cardiothoracic Surgery
- Hovedetterforsker: R. A. de Boer, dr, MD, University Medical Center Groningen, Dept of Cardiology
- Studieleder: D. J. van Veldhuisen, Prof, dr, MD, University Medical Center Groningen, Dept. of Cardiology
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Hjelpsomme linker
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. september 2007
Primær fullføring (Faktiske)
1. januar 2011
Studiet fullført (Faktiske)
1. april 2011
Datoer for studieregistrering
Først innsendt
4. september 2007
Først innsendt som oppfylte QC-kriteriene
4. september 2007
Først lagt ut (Anslag)
5. september 2007
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
15. februar 2013
Siste oppdatering sendt inn som oppfylte QC-kriteriene
13. februar 2013
Sist bekreftet
1. februar 2013
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- WTR-ECG-2
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