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

NCT ID: NCT00390832

Last Updated: 2010-12-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2009-03-31

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.

Conditions

Myocardial Infarction; Angioplasty, Transluminal, Percutaneous Coronary

Keywords

STEMI

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

A

recombinant human erythropoietin beta

Group Type: ACTIVE_COMPARATOR

Erythropoietin

Intervention Type: DRUG

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

0.9% NaCl solution

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Patients will receive placebo immediately, 24 hours and 48 hours after percutaneous coronary intervention.

Interventions

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

Intervention Type: DRUG

Placebo

Patients will receive placebo immediately, 24 hours and 48 hours after percutaneous coronary intervention.

Intervention Type: OTHER

Other Intervention Names

NeoRecormon; 0.9% NaCl

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®)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deutsches Herzzentrum Muenchen

OTHER

Sponsor Role: lead

Responsible Party

Deutsches Herzzentrum Munich

Principal Investigators

Albert Schomig, MD

Role: STUDY_CHAIR

Deutsches Herzzentrum Muenchen

Ilka Ott, MD

Role: PRINCIPAL_INVESTIGATOR

Deutsches Herzzentrum Muenchen

Locations

Deutsches Herzzentrum Muenchen

Munich, , Germany

1. Medizinische Klinik, Klinikum rechts der Isar

Munich, , Germany

Countries

Germany

References

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Reference Type: BACKGROUND

PMID: 11918909 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16325031 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15215812 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9875214 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15294194 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12435860 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20736448 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28109258 (View on PubMed)

Other Identifiers

GE IDE No. I01106

Identifier Type: -

Identifier Source: org_study_id