Efficacy Study of Erythropoietin After Revascularization in Myocardial Infarction (REVIVAL-3) (REVIVAL-3)
Primary Purpose
Myocardial Infarction, Angioplasty, Transluminal, Percutaneous Coronary
Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Erythropoietin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Myocardial Infarction focused on measuring STEMI
Eligibility 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®)
Sites / Locations
- Deutsches Herzzentrum Muenchen
- 1. Medizinische Klinik, Klinikum rechts der Isar
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
A
B
Arm Description
recombinant human erythropoietin beta
0.9% NaCl solution
Outcomes
Primary Outcome Measures
Left ventricular ejection fraction measured by magnetic resonance imaging
Secondary Outcome Measures
Changes in left ventricular ejection fraction and infarct size
Death, recurrent myocardial infarction, IRA-revascularization and stroke
Full Information
NCT ID
NCT00390832
First Posted
October 19, 2006
Last Updated
December 16, 2010
Sponsor
Deutsches Herzzentrum Muenchen
1. Study Identification
Unique Protocol Identification Number
NCT00390832
Brief Title
Efficacy Study of Erythropoietin After Revascularization in Myocardial Infarction (REVIVAL-3)
Acronym
REVIVAL-3
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)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2009
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
March 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Deutsches Herzzentrum Muenchen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Infarction, Angioplasty, Transluminal, Percutaneous Coronary
Keywords
STEMI
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
138 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Active Comparator
Arm Description
recombinant human erythropoietin beta
Arm Title
B
Arm Type
Placebo Comparator
Arm Description
0.9% NaCl solution
Intervention Type
Drug
Intervention Name(s)
Erythropoietin
Other Intervention Name(s)
NeoRecormon
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
0.9% NaCl
Intervention Description
Patients will receive placebo immediately, 24 hours and 48 hours after percutaneous coronary intervention.
Primary Outcome Measure Information:
Title
Left ventricular ejection fraction measured by magnetic resonance imaging
Time Frame
4-6 months
Secondary Outcome Measure Information:
Title
Changes in left ventricular ejection fraction and infarct size
Time Frame
over 6 months
Title
Death, recurrent myocardial infarction, IRA-revascularization and stroke
Time Frame
30 days, 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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®)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Albert Schomig, MD
Organizational Affiliation
Deutsches Herzzentrum Muenchen
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Ilka Ott, MD
Organizational Affiliation
Deutsches Herzzentrum Muenchen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Deutsches Herzzentrum Muenchen
City
Munich
ZIP/Postal Code
80636
Country
Germany
Facility Name
1. Medizinische Klinik, Klinikum rechts der Isar
City
Munich
ZIP/Postal Code
81675
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
11918909
Citation
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Results Reference
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PubMed Identifier
16325031
Citation
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. doi: 10.1016/j.jacc.2005.07.060. Epub 2005 Nov 4.
Results Reference
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PubMed Identifier
15215812
Citation
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. doi: 10.1016/j.ahj.2004.01.019.
Results Reference
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PubMed Identifier
9875214
Citation
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. doi: 10.1006/bbrc.1998.9748.
Results Reference
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PubMed Identifier
15294194
Citation
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. doi: 10.1016/j.transci.2004.05.001.
Results Reference
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PubMed Identifier
12435860
Citation
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.
Results Reference
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PubMed Identifier
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Citation
Ott I, Schulz S, Mehilli J, Fichtner S, Hadamitzky M, Hoppe K, Ibrahim T, Martinoff S, Massberg S, Laugwitz KL, Dirschinger J, Schwaiger M, Kastrati A, Schmig A; REVIVAL-3 Study Investigators. Erythropoietin in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomized, double-blind trial. Circ Cardiovasc Interv. 2010 Oct;3(5):408-13. doi: 10.1161/CIRCINTERVENTIONS.109.904425. Epub 2010 Aug 24.
Results Reference
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PubMed Identifier
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Citation
Steppich B, Groha P, Ibrahim T, Schunkert H, Laugwitz KL, Hadamitzky M, Kastrati A, Ott I; Regeneration of Vital Myocardium in ST-Segment Elevation Myocardial Infarction by Erythropoietin (REVIVAL-3) Study Investigators. Effect of Erythropoietin in patients with acute myocardial infarction: five-year results of the REVIVAL-3 trial. BMC Cardiovasc Disord. 2017 Jan 21;17(1):38. doi: 10.1186/s12872-016-0464-3.
Results Reference
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Efficacy Study of Erythropoietin After Revascularization in Myocardial Infarction (REVIVAL-3)
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