- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT00524901
Study of the Use of a Single Dose of Erythropoietin to Treat Acute Myocardial Ischemia (DREAM)
13 februari 2013 uppdaterad 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.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Studietyp
Interventionell
Inskrivning (Faktisk)
10
Fas
- Fas 2
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
-
Groningen, Nederländerna, 9700 BD
- University Medical Center Groningen, Dept. of Cardiology
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år till 80 år (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: 1
25 patients undergoing CABG for three vessel disease, receiving a single dose of erythropoietin periprocedural.
|
A single dose of epoetin alpha during CABG for three vessel disease, 60.000 IU intravenously.
Andra namn:
|
|
Placebo-jämförare: 2
25 patients undergoing CABG for three vessel disease, receiving placebo (NaCl 0.9%) periprocedural.
|
A single dose of NaCl 0.9% during CABG for three vessel disease, 1 ml intravenously.
Andra namn:
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Tidsram |
|---|---|
|
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.
Tidsram: 2 hours
|
2 hours
|
Sekundära resultatmått
Resultatmått |
Tidsram |
|---|---|
|
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.
Tidsram: 2 hours
|
2 hours
|
|
Difference between EPO- and saline treated subjects in TUNEL and active caspase-3 positive cells in ventricular and atrial biopsies.
Tidsram: 2 hours
|
2 hours
|
|
Difference in AUC for CK-MB, Troponin T, NT-proBNP, and cystatin C between EPO- and saline treated patients.
Tidsram: 30 days
|
30 days
|
|
Subject incidence rates of adverse events.
Tidsram: 30 days
|
30 days
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Utredare
- Studiestol: W. H. van Gilst, Prof, dr, University Medical Center Groningen, Dept. of Exprimental Cardiology
- Huvudutredare: W. T. Ruifrok, MD, University Medical Center Groningen, Dept. of Experimental Cardiology
- Huvudutredare: B. D. Westenbrink, MD, University Medical Center Groningen, Dept. of Experimental Cardiology
- Huvudutredare: A. H. Epema, dr, MD, University Medical Center Groningen, Dept. of Anaesthesiology
- Huvudutredare: H. E. Mungroop, dr, MD, University Medical Center Groningen, Dept. of Anaesthesiology
- Huvudutredare: P. W. Boonstra, Prof, dr, MD, University Medical Center Groningen, Dept. of Cardiothoracic Surgery
- Huvudutredare: R. A. de Boer, dr, MD, University Medical Center Groningen, Dept of Cardiology
- Studierektor: D. J. van Veldhuisen, Prof, dr, MD, University Medical Center Groningen, Dept. of Cardiology
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Användbara länkar
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 september 2007
Primärt slutförande (Faktisk)
1 januari 2011
Avslutad studie (Faktisk)
1 april 2011
Studieregistreringsdatum
Först inskickad
4 september 2007
Först inskickad som uppfyllde QC-kriterierna
4 september 2007
Första postat (Uppskatta)
5 september 2007
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
15 februari 2013
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
13 februari 2013
Senast verifierad
1 februari 2013
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- WTR-ECG-2
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .