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

Myocardial Ischemic Reperfusion Injury Clinical Trial

Official title:

Placebo- Controlled,Randomized,Double Blind Trial of Erythropoietin Effect on Ischemic_ Reperfusion Injury in Coronary Artery Bypass Graft Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02984111
• Other study ID #: IR.sbmu.ram.rec.1394.292
• Secondary ID: IRCT201601162108
• Status: Completed
• Phase: N/A
• First received: November 13, 2016
• Last updated: October 22, 2017
• Start date: January 2016
• Est. completion date: June 2017

Study information

• Verified date: October 2017
• Source: Shahid Beheshti University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

In addition to well-known effect of Erythropoietin (EPO) on erythropoiesis in hypoxic conditions, some lines of evidence suggest its protective effects against reperfusion injury in several tissues by its specific receptor.

Preclinical studies have indicated a broad variety of cardioprotective actions for EPO. It improves cardiac function and exercise capacity in congestive heart failure, angiogenesis, limit myocardial inflammatory response, cardiac remodeling, infarct size and apoptosis extension induced by reperfusion injury. Activation of EPO receptor in endothelial and cardiac cells is suggested to attenuate proinflammatory cytokines production and inflammatory cells infiltration, and increasing nitric oxide production through possible mechanisms.

Reperfusion injury is unavoidable event during cardiac surgery using cardiopulmonary bypass.It is associated with inflammation, cell injury and attenuate contractility property.

Although it is an area of concern and many clinical studies have been designed by different interventions, it remains a major challenge. EPO intervention during heart reperfusion (surgery/ percutaneous angioplasty) as a new promise of cardioprotection strategy is the main design of several studies with conflicting results .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: June 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Ischemia
• Myocardial Ischemic Reperfusion Injury
• Myocardial Reperfusion Injury
• Reperfusion Injury
• Wounds and Injuries

Intervention

Drug:
• normal saline

• erythropoietin

Locations

Country	Name	City	State
Iran, Islamic Republic of	Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences.	Tehran

Sponsors (2)

Lead Sponsor	Collaborator
Shahid Beheshti University of Medical Sciences	Pooyesh Darou

Country where clinical trial is conducted

Iran, Islamic Republic of, 

References & Publications (18)

Bergmann MW, Haufe S, von Knobelsdorff-Brenkenhoff F, Mehling H, Wassmuth R, Münch 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, f — View Citation

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 pati — View Citation

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. Review. — View Citation

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. — View Citation

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) — View Citation

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. — View Citation

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. Erratum in: Heart. 2011 Nov;97(21):1812. Mutharangu, Vivek [corrected to Muthurangu, Vivek]. — View Citation

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 und — View Citation

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. — View 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. — View Citation

Poulsen TD, Andersen LW, Steinbrüchel D, Gøtze JP, Jørgensen 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/ — View Citation

Prunier F, Bière L, Gilard M, Boschat J, Mouquet F, Bauchart JJ, Charbonnier B, Genée O, Guérin P, Warin-Fresse K, Durand E, Lafont A, Christiaens L, Abi-Khalil W, Delépine S, Benard T, Furber A. Single high-dose erythropoietin administration immediately — View Citation

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, ran — View Citation

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/ — View Citation

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 myocard — View Citation

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):6 — View Citation

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. — View Citation

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. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Volume of bleeding		During operation until 24 hours after surgery
Secondary	Need to blood transfusion	Number of packed cell and fresh frozen plasma that transfused in the period of time that patient is hospitalized.	During and after operation, through study completion,an average of one week
Secondary	Ventilation time		Period of time after surgery that patient has been intubated in ICU,an average of 10 hours