Preliminary Administration of EPO and Markers of Cardiac Ischemia Induced by CPB

Myocardial Ischemia Clinical Trial

— EPOetCEC  

Official title:

Double-blind Phase II Pilot Monocentric Randomized Clinical Trial Evaluating the Effect of a Preliminary Administration of Erythropoietin on Different Markers of Cardiac Ischemia Induced by Cardiopulmonary Bypass

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00273767
• Other study ID #: DCIC 05 04
• Status: Completed
• Phase: Phase 2
• First received: January 6, 2006
• Last updated: December 4, 2009
• Start date: January 2006
• Est. completion date: November 2009

Study information

• Verified date: December 2009
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

The main objective is to observe the effects of erythropoietin administration on different blood markers of ischaemic cardiac lesions induced by cardiopulmonary bypass.

Description:

A new property of erythropoietin (EPO), independent of its hematopoietic role, has recently been discovered. Indeed, it has been reported that this hormone, following binding to its cardiac or cerebral receptors, is able to induce a spectacular cellular protection against ischemic injury. These cardioprotective and neuroprotective effects have been observed experimentally in rodents as well as clinically in humans. In particular, our team has demonstrated that the administration of NeoRecormon® protects the heart against ischemia in the rat by significantly improving its recovery.

In view of these exciting experimental results and of the growing interest of the scientific community for cytoprotective effects of EPO, we are planning the first clinical study examining the cardiac and cerebral protective effects of EPO (NeoRecormon®) in the setting of cardiac surgery.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: November 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Coronary bypass surgery.

• Surgery not urgent.

• Left ventricular ejection fraction (LVEF) > 40.

• Informed consent form signed.

Exclusion Criteria:

• Valvular surgery.

• Surgery with beating heart, with or without cardiopulmonary bypass.

• Carotid bypass surgery.

• Myocardial infarction less than 30 days.

• Previous history of cardiac surgery.

• Kidney failure (creatinine > 200 µmol/l).

• Uncontrolled hypertension.

• Unstable angina.

• Risk of deep venous thrombosis.

• Vascular cerebral attack less than 30 days.

• Malignant tumour.

• Phenylketonuria.

• Allergy to erythropoietin.

• Previous programmed blood donation.

• Pregnancy and feeding.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Coronary Artery Disease
• Ischemia
• Myocardial Ischemia

Intervention

Drug:
• epoetin beta
800UI/kg in 60ml of Nacl IV slow 1 to 3 hours before surgery
• placebo
60ml of NaCl IV slow

Locations

Country	Name	City	State
France	Cardiac Surgery Department - CHU de Grenoble	Grenoble

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Grenoble	Roche Pharma AG

Country where clinical trial is conducted

France, 

References & Publications (5)

Bogoyevitch MA. An update on the cardiac effects of erythropoietin cardioprotection by erythropoietin and the lessons learnt from studies in neuroprotection. Cardiovasc Res. 2004 Aug 1;63(2):208-16. Review. — View 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, Rüther E, Kochen M, Gefeller O, Gleiter C, Wessel TC, De Ryck M, Itri L, Prange H, Cerami A, Brines M, Sirén AL. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med. 2002 Aug;8(8):495-505. — View Citation

Johnsson P, Bäckström M, Bergh C, Jönsson H, Lührs C, Alling C. Increased S100B in blood after cardiac surgery is a powerful predictor of late mortality. Ann Thorac Surg. 2003 Jan;75(1):162-8. — View Citation

Joyeux-Faure M, Godin-Ribuot D, Ribuot C. Erythropoietin and myocardial protection: what's new? Fundam Clin Pharmacol. 2005 Aug;19(4):439-46. Review. — View Citation

Kerbaul F, Giorgi R, Oddoze C, Collart F, Guidon C, Lejeune PJ, Villacorta J, Gouin F. High concentrations of N-BNP are related to non-infectious severe SIRS associated with cardiovascular dysfunction occurring after off-pump coronary artery surgery. Br J Anaesth. 2004 Nov;93(5):639-44. Epub 2004 Sep 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under curve and maximal plasmatic level of troponin-T, NT-pro-BNP, and creatine kinase-MB (CK-MB) after cardiopulmonary bypass		at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), puis 6 h, 12 h, 24 h et 48h after the end of the cardiopulmonary bypass	Yes
Secondary	Area under curve and maximal plasmatic level of protein S-100 after cardiopulmonary bypass		at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), puis 6 h, 12 h, 24 h et 48h after the end of the cardiopulmonary bypass	Yes
Secondary	Blood level of erythropoietin		at injection and 6 hours after the end of cardiopulmonary bypass	No