Clinical trial NCT00273767: Preliminary Administration of EPO and Markers of Cardiac Ischemia Induced by CPB
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myocardial Ischemia
Keywords: troponin T
CK-MB
protein S-100
Cardiopulmonary Bypass
Erythropoietin
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2006-01-09
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Area under curve and maximal plasmatic level of troponin-T, NT-pro-BNP, and creatine kinase-MB (CK-MB) after cardiopulmonary bypass
timeFrame: 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
Secondary outcomes:
measure: Area under curve and maximal plasmatic level of protein S-100 after cardiopulmonary bypass
timeFrame: 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
measure: Blood level of erythropoietin
timeFrame: at injection and 6 hours after the end of cardiopulmonary bypass
Other outcomes:
Locations:
city: Grenoble
country: France
facility: Cardiac Surgery Department - CHU de Grenoble
Study officials:
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Olivier CHAVANON, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1016/j.cardiores.2004.03.017.
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.
citation: Johnsson P, Backstrom M, Bergh C, Jonsson H, Luhrs 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. doi: 10.1016/s0003-4975(02)04318-7.
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. doi: 10.1111/j.1472-8206.2005.00347.x.
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. doi: 10.1093/bja/aeh246. Epub 2004 Sep 3.