Efficacy Study of Erythropoietin After Revascularization in Myocardial Infarction (REVIVAL-3) - Full Text View

Sponsored by:	Deutsches Herzzentrum Muenchen
Information provided by:	Deutsches Herzzentrum Muenchen
ClinicalTrials.gov Identifier:	NCT00390832

Purpose

The purpose of this study is to determine whether erythropoietin is superior to placebo with respect to left ventricular ejection fraction in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention.

Condition	Intervention	Phase
Myocardial Infarction Angioplasty, Transluminal, Percutaneous Coronary	Drug: Erythropoietin Other: Placebo	Phase III

MedlinePlus related topics: Heart Attack

Drug Information available for: Epoetin alfa Erythropoietin Epoetin beta

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of Erythropoietin in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention (REVIVAL-3)

Further study details as provided by Deutsches Herzzentrum Muenchen:

Primary Outcome Measures:

Left ventricular ejection fraction measured by magnetic resonance imaging [ Time Frame: 4-6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Changes in left ventricular ejection fraction and infarct size measured by MRI [ Time Frame: 4-6 months ] [ Designated as safety issue: No ]
Death, recurrent myocardial infarction, repeat infarct artery revascularization and stroke [ Time Frame: 30 days, 6 months ] [ Designated as safety issue: Yes ]

Enrollment:	138
Study Start Date:	December 2006
Estimated Study Completion Date:	March 2009
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator recombinant human erythropoietin beta	Drug: Erythropoietin 33.333 IU of recombinant human erythropoietin beta are given at 3 time points (immediately, 24 hours and 48 hours after percutaneous coronary intervention) providing a cumulative dose of 100.000 IU
B: Placebo Comparator 0.9% NaCl solution	Other: Placebo Patients will receive placebo immediately, 24 hours and 48 hours after percutaneous coronary intervention.

Detailed Description:

Erythropoietin has lately been shown to exert others than merely hematopoietic functions. Due to attenuation of cell apoptosis and necrosis and/or enhancing neovascularisation, erythropoietin could be protective after myocardial ischemia and reperfusion and lead to infarct size reduction and improvement in left ventricular function. In a controlled clinical trial, short-term administration of erythropoietin in patients with ischemic stroke was associated with a significantly better functional recovery, with a lower level of circulating damage markers and a strong trend to smaller infarct sizes measured by magnetic resonance imaging. While leaving hematocrit and platelet counts unchanged, short-term administration of erythropoietin was shown to be safe and very well tolerated (no side effects reported or observed). The protective effects of short-term erythropoietin in acute ischemic brain damage are further evaluated in an ongoing multi-center trial in Germany. Considering the preclinical and clinical data erythropoietin is an attractive candidate to be evaluated in patients with acute myocardial infarction. In a pilot trial enrolling 22 patients with acute myocardial infarction short-term administration of erythropoietin was shown to be safe and to significantly increase the level of endothelial progenitor cells after percutaneous coronary intervention. However, the very small population did not allow evaluating the benefit in left ventricular function or clinical outcomes.

The aim of the REVIVAL-3 study is to investigate whether there is additional benefit of short-term administration of erythropoietin in patients with acute myocardial infarction after successful primary percutaneous coronary intervention (PCI) in terms of left ventricular ejection fraction.

Eligibility

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

Criteria

Inclusion Criteria:

Patients with ST-Segment elevation myocardial infarction <24 h from pain onset
Successful primary PCI and left ventricular ejection fraction <50%
Informed, written consent
In women with childbearing potential a pregnancy test is mandatory

Exclusion Criteria:

Age < 18 and > 80 years
Cardiogenic shock
pericarditis
thrombolysis for the index infarction
malignancies/other comorbid conditions with life expectancy < 1 year
previous myocardial infarction
planned staged PCI or prior PCI within 30 days from index procedure
uncontrolled hypertension >160/100mmHg unresponsive to therapy
epilepsy
active bleeding; bleeding diathesis; history of gastrointestinal or genitourinary bleeding, recent trauma or major surgery < 1 month; history of intracranial bleeding or structural abnormalities; suspected aortic dissection; patient's refusal to blood transfusion
hematologic disorders such as essential thrombocytosis, megakaryoblastic leukemia, polycythemia vera
relevant hematologic deviations: hemoglobin < 100 g/l or hemoglobin > 160 g/l platelet count < 100 x 10^9 cells/l or platelet count > 600 x 10^9 cells/l
any contraindication to magnetic resonance imaging: electronically, magnetically and mechanically activated implants such as cardiac pacemakers, automatic cardioverter defibrillators, joint prostheses, surgical/vascular clips/ hearing aids, neurostimulators, infusion pumps etc metallic splinters in the eye ferromagnetic haemostatic clips in the central nervous system cochlear implants lead wires or similar wires prosthetic heart valves, if dehiscence is suspected non-ferromagnetic stapedial implants, hemostatic clips
glomerular filtration rate < 30 ml/min or serum creatinine > 30 mg/l or dependence on renal dialysis
chronic liver disease with GOT > 5-fold over the normal range
allergy to erythropoietin/true anaphylaxis after prior exposure to contrast media
phenylketonuria
previous enrollment in this trial
women who are known to be pregnant, who are of childbearing potential and test positive for pregnancy, who have given birth within the last 90 days, who are breastfeeding
patient's inability to fully cooperate with the study protocol
other contraindication according to the summary of product characteristics of recombinant human erythropoietin beta (NeoRecormon®)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00390832

Locations

Germany
Deutsches Herzzentrum Muenchen
Munich, Germany, 80636
1. Medizinische Klinik, Klinikum rechts der Isar
Munich, Germany, 81675

Sponsors and Collaborators

Deutsches Herzzentrum Muenchen

Investigators

Study Chair:	Albert Schoemig, MD	Deutsches Herzzentrum Muenchen
Principal Investigator:	Ilka Ott, MD	Deutsches Herzzentrum Muenchen

More Information

Publications:

Kastrati A, Mehilli J, Dirschinger J, Schricke U, Neverve J, Pache J, Martinoff S, Neumann FJ, Nekolla S, Blasini R, Seyfarth M, Schwaiger M, Schomig A; Stent versus Thrombolysis for Occluded Coronary Arteries in Patients With Acute Myocardial Infarction (STOPAMI-2) Study. Myocardial salvage after coronary stenting plus abciximab versus fibrinolysis plus abciximab in patients with acute myocardial infarction: a randomised trial. Lancet. 2002 Mar 16;359(9310):920-5.

Zohlnhofer D, Hausleiter J, Kastrati A, Mehilli J, Goos C, Schuhlen H, Pache J, Pogatsa-Murray G, Heemann U, Dirschinger J, Schomig A. A randomized, double-blind, placebo-controlled trial on restenosis prevention by the receptor tyrosine kinase inhibitor imatinib. J Am Coll Cardiol. 2005 Dec 6;46(11):1999-2003. Epub 2005 Nov 4.

Pache J, Kastrati A, Mehilli J, Bollwein H, Ndrepepa G, Schuhlen H, Martinoff S, Seyfarth M, Nekolla S, Dirschinger J, Schwaiger M, Schomig A. A randomized evaluation of the effects of glucose-insulin-potassium infusion on myocardial salvage in patients with acute myocardial infarction treated with reperfusion therapy. Am Heart J. 2004 Jul;148(1):e3.

Sadamoto Y, Igase K, Sakanaka M, Sato K, Otsuka H, Sakaki S, Masuda S, Sasaki R. Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery. Biochem Biophys Res Commun. 1998 Dec 9;253(1):26-32.

Ehrenreich H, Timner W, Siren AL. A novel role for an established player: anemia drug erythropoietin for the treatment of cerebral hypoxia/ischemia. Transfus Apher Sci. 2004 Aug;31(1):39-44. Review.

Ehrenreich H, Hasselblatt M, Dembowski C, Cepek L, Lewczuk P, Stiefel M, Rustenbeck HH, Breiter N, Jacob S, Knerlich F, Bohn M, Poser W, Ruther E, Kochen M, Gefeller O, Gleiter C, Wessel TC, De Ryck M, Itri L, Prange H, Cerami A, Brines M, Siren AL. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med. 2002 Aug;8(8):495-505.

Responsible Party:	Deutsches Herzzentrum Munich ( Prof. A. Schömig )
Study ID Numbers:	GE IDE No. I01106
Study First Received:	October 19, 2006
Last Updated:	January 6, 2009
ClinicalTrials.gov Identifier:	NCT00390832
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Deutsches Herzzentrum Muenchen:

STEMI

Study placed in the following topic categories:

Epoetin Alfa
Necrosis
Heart Diseases
Myocardial Ischemia

Vascular Diseases
Ischemia
Infarction
Myocardial Infarction

Additional relevant MeSH terms:

Pathologic Processes
Hematinics
Therapeutic Uses

Hematologic Agents
Cardiovascular Diseases
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009