Erythropoietin Effect on Ischemic_ Reperfusion Injury in Coronary Artery Bypass Graft Surgery

NCT02984111 | Completed DMC

• 2 other identifiers: IR.sbmu.ram.rec.1394.292IRCT2016011621087N1
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this trail is to assess the safety and therapeutic effects of single EPO intervention in different times during coronary surgery in changes of inflammatory response.

Conditions

Myocardial Ischemic Reperfusion Injury

Keywords

Coronary artery bypass; Erythropoietin; Inflammation; IL-6; Reperfusion injury; YKL- 40

Outcome Measures

Primary Outcomes (3)

• Change in Interleukin 6(IL6)

  Serum IL6(an inflammatory marker) level is measured before operation (base),just after operation,24 hours after operation,48 hours after operation

  Change from baseline until 48 hours after surgery

• Change in YKL-40

  Chitinase-3-like protein 1 (CHI3L1), also known as YKL-40 is an inflammatory marker.Serum YKL-40 level is measured before operation (base),just after operation,24 hours after operation,48 hours after operation

  Change from baseline until 48 hours after surgery

• Change in pro b-type natriuretic peptide(pro BNP)

  Serum pro BNP level is measured before operation (base),just after operation,24 hours after operation,48 hours after operation

  Change from baseline until 48 hours after surgery

Secondary Outcomes (3)

• Volume of bleeding

  During operation until 24 hours after surgery

• Need to blood transfusion

  During and after operation, through study completion,an average of one week

• Ventilation time

  Period of time after surgery that patient has been intubated in ICU,an average of 10 hours

Study Arms (3)

group A

ACTIVE COMPARATOR

20000 IU erythropoietin infusion during aortic cross clamp in 45-60 minutes

Drug: erythropoietin

group B

ACTIVE COMPARATOR

20000 IU erythropoietin infusion after induction of anesthesia and before undergoing cardiopulmonary bypass pump in 45-60 minutes

Drug: erythropoietin

control

PLACEBO COMPARATOR

50 ml normal saline infusion during aortic cross clamp in 45-60 minutes

Drug: normal saline

Interventions

normal saline DRUG

Also known as: N/S

control

erythropoietin DRUG

Also known as: epoietin alfa

group A; group B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Revascularization requirement according to angiographic evidence
• Elective coronary artery bypass graft surgery
• First time coronary artery bypass graft surgery
• On-pump coronary artery bypass graft surgery

You may not qualify if:

• History of myocardial infarction in the past 3 months
• Previous myocardial trauma or major surgery in the past 3 months
• Cr\>2mg/dl
• Receiving streptokinase or previous reperfusion treatments
• Erythropoietin intake in the recent 6 months
• Known thromboembolic disorder and malignant disease
• Uncontrolled hypertension
• Polycythemia
• Previous valvular surgery

Sponsors & Collaborators

• Shahid Beheshti University of Medical Sciences: lead
• Pooyesh Darou: collaborator

Study Sites (1)

Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences.

Tehran, 199873438, Iran

Location

Related Publications (18)

• Ziabakhsh-Tabary S, Jalalian R, Mokhtari-Esbuie F, Habibi MR. Echocardiographic Evaluation of the Effects of a Single Bolus of Erythropoietin on Reducing Ischemia-Reperfusion Injuries during Coronary Artery Bypass Graft Surgery; A Randomized, Double-Blind, Placebo-Control Study. Iran J Med Sci. 2014 Mar;39(2):94-101.

  PMID: 24644377 BACKGROUND

• Ludman AJ, Yellon DM, Hasleton J, Ariti C, Babu GG, Boston-Griffiths E, Venugopal V, Walker M, Holdright D, Swanton H, Crake T, Brull D, Moon JC, Puranik R, Muthurangu V, Taylor A, Hausenloy DJ. Effect of erythropoietin as an adjunct to primary percutaneous coronary intervention: a randomised controlled clinical trial. Heart. 2011 Oct;97(19):1560-5. doi: 10.1136/hrt.2011.223867.

  PMID: 21900585 BACKGROUND

• Joyeux-Faure M, Durand M, Bedague D, Protar D, Incagnoli P, Paris A, Ribuot C, Levy P, Chavanon O. Evaluation of the effect of one large dose of erythropoietin against cardiac and cerebral ischemic injury occurring during cardiac surgery with cardiopulmonary bypass: a randomized double-blind placebo-controlled pilot study. Fundam Clin Pharmacol. 2012 Dec;26(6):761-70. doi: 10.1111/j.1472-8206.2011.00992.x. Epub 2011 Sep 20.

  PMID: 21929528 BACKGROUND

• Najjar SS, Rao SV, Melloni C, Raman SV, Povsic TJ, Melton L, Barsness GW, Prather K, Heitner JF, Kilaru R, Gruberg L, Hasselblad V, Greenbaum AB, Patel M, Kim RJ, Talan M, Ferrucci L, Longo DL, Lakatta EG, Harrington RA; REVEAL Investigators. Intravenous erythropoietin in patients with ST-segment elevation myocardial infarction: REVEAL: a randomized controlled trial. JAMA. 2011 May 11;305(18):1863-72. doi: 10.1001/jama.2011.592.

  PMID: 21558517 BACKGROUND

• 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.

  PMID: 20736448 BACKGROUND

• Vilarinho KA, de Oliveira PP, Saad MJ, Eghtesady P, Filho LM, Vieira RW, Petrucci O. Erythropoietin protects the systolic function of neonatal hearts against ischaemia/reperfusion injury. Eur J Cardiothorac Surg. 2013 Jan;43(1):156-62. doi: 10.1093/ejcts/ezs254. Epub 2012 May 7.

  PMID: 22564802 RESULT

• Watson AJ, Gao L, Sun L, Tsun J, Jabbour A, Ru Qiu M, Jansz PC, Hicks M, Macdonald PS. Enhanced preservation of the rat heart after prolonged hypothermic ischemia with erythropoietin-supplemented Celsior solution. J Heart Lung Transplant. 2013 Jun;32(6):633-40. doi: 10.1016/j.healun.2013.03.014.

  PMID: 23701853 RESULT

• Lu MJ, Chen YS, Huang HS, Ma MC. Erythropoietin alleviates post-ischemic injury of rat hearts by attenuating nitrosative stress. Life Sci. 2012 May 22;90(19-20):776-84. doi: 10.1016/j.lfs.2012.04.012. Epub 2012 Apr 12.

  PMID: 22521289 RESULT

• Xu X, Cao Z, Cao B, Li J, Guo L, Que L, Ha T, Chen Q, Li C, Li Y. Carbamylated erythropoietin protects the myocardium from acute ischemia/reperfusion injury through a PI3K/Akt-dependent mechanism. Surgery. 2009 Sep;146(3):506-14. doi: 10.1016/j.surg.2009.03.022. Epub 2009 Jun 9.

  PMID: 19715808 RESULT

• Prunier F, Biere L, Gilard M, Boschat J, Mouquet F, Bauchart JJ, Charbonnier B, Genee O, Guerin P, Warin-Fresse K, Durand E, Lafont A, Christiaens L, Abi-Khalil W, Delepine S, Benard T, Furber A. Single high-dose erythropoietin administration immediately after reperfusion in patients with ST-segment elevation myocardial infarction: results of the erythropoietin in myocardial infarction trial. Am Heart J. 2012 Feb;163(2):200-7.e1. doi: 10.1016/j.ahj.2011.11.005.

  PMID: 22305837 RESULT

• Voors AA, Belonje AM, Zijlstra F, Hillege HL, Anker SD, Slart RH, Tio RA, van 't Hof A, Jukema JW, Peels HO, Henriques JP, Ten Berg JM, Vos J, van Gilst WH, van Veldhuisen DJ; HEBE III Investigators. A single dose of erythropoietin in ST-elevation myocardial infarction. Eur Heart J. 2010 Nov;31(21):2593-600. doi: 10.1093/eurheartj/ehq304. Epub 2010 Aug 29.

  PMID: 20802250 RESULT

• Momeni M, Liistro G, Baele P, Matta A, Kahn D, Van Dyck M, De Kock M, De Kerchove L, Glineur D, Thiry D, Gregoire A, Jacquet LM, Laarbui F, Watremez C. An increase in endogenous erythropoietin concentrations has no cardioprotective effects in patients undergoing coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth. 2012 Apr;26(2):251-7. doi: 10.1053/j.jvca.2011.07.034. Epub 2011 Oct 5.

  PMID: 21975293 RESULT

• Taniguchi N, Nakamura T, Sawada T, Matsubara K, Furukawa K, Hadase M, Nakahara Y, Nakamura T, Matsubara H. Erythropoietin prevention trial of coronary restenosis and cardiac remodeling after ST-elevated acute myocardial infarction (EPOC-AMI): a pilot, randomized, placebo-controlled study. Circ J. 2010 Nov;74(11):2365-71. doi: 10.1253/circj.cj-10-0267. Epub 2010 Sep 8.

  PMID: 20834185 RESULT

• Bergmann MW, Haufe S, von Knobelsdorff-Brenkenhoff F, Mehling H, Wassmuth R, Munch I, Busjahn A, Schulz-Menger J, Jordan J, Luft FC, Dietz R. A pilot study of chronic, low-dose epoetin-beta following percutaneous coronary intervention suggests safety, feasibility, and efficacy in patients with symptomatic ischaemic heart failure. Eur J Heart Fail. 2011 May;13(5):560-8. doi: 10.1093/eurjhf/hfr002.

  PMID: 21505058 RESULT

• Ferrario M, Arbustini E, Massa M, Rosti V, Marziliano N, Raineri C, Campanelli R, Bertoletti A, De Ferrari GM, Klersy C, Angoli L, Bramucci E, Marinoni B, Ferlini M, Moretti E, Raisaro A, Repetto A, Schwartz PJ, Tavazzi L. High-dose erythropoietin in patients with acute myocardial infarction: a pilot, randomised, placebo-controlled study. Int J Cardiol. 2011 Feb 17;147(1):124-31. doi: 10.1016/j.ijcard.2009.10.028. Epub 2009 Nov 10.

  PMID: 19906454 RESULT

• Poulsen TD, Andersen LW, Steinbruchel D, Gotze JP, Jorgensen OS, Olsen NV. Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery. J Cardiothorac Vasc Anesth. 2009 Jun;23(3):316-23. doi: 10.1053/j.jvca.2008.08.018. Epub 2008 Oct 22.

  PMID: 18948032 RESULT

• Kagaya Y, Asaumi Y, Wang W, Takeda M, Nakano M, Satoh K, Fukumoto Y, Shimokawa H. Current perspectives on protective roles of erythropoietin in cardiovascular system: erythropoietin receptor as a novel therapeutic target. Tohoku J Exp Med. 2012 Jun;227(2):83-91. doi: 10.1620/tjem.227.83.

  PMID: 22688525 RESULT

• Gobe GC, Morais C, Vesey DA, Johnson DW. Use of high-dose erythropoietin for repair after injury: A comparison of outcomes in heart and kidney. J Nephropathol. 2013 Jul;2(3):154-65. doi: 10.12860/JNP.2013.27. Epub 2013 Jul 1.

  PMID: 24475445 RESULT

MeSH Terms

Conditions

Myocardial Reperfusion Injury; Inflammation; Reperfusion Injury

Interventions

Saline Solution; Erythropoietin

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Myocardial Ischemia; Vascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Mahnoosh Foroughi, MD,

  Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences. Tehran, Iran.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: November 13, 2016
• First Posted: December 6, 2016
• Study Start: January 1, 2016
• Primary Completion: January 1, 2017
• Study Completion: June 1, 2017
• Last Updated: October 24, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)