Clinical trial NCT01608984: Effects of Remote Ischemic PreConditioning in Off-pump Versus On-pump Coronary Artery Bypass Grafting(RIPCON)
Official title: Effects of Remote Ischemic PreConditioning in Off-pump Versus On-pump Coronary
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Myocardial Injury
Keywords: remote ischemic preconditioning
coronary artery bypass grafting
myocardial injury
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
Collaborators: name: University Hospital, Essen
First posted: 2012-05-31
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Purpose Remote ischemic preconditioning (RIPC) with transient upper limb ischemia reduces myocardial injury in patients undergoing On-pump coronary artery bypass (CABG) surgery with cross-clamp fibrillation or blood cardioplegia for myocardial protection. The molecular mechanisms leading to these effects are yet not fully understood. The purpose of the present study is to validate previous studies and gather further evidence for RIPC during CABG with blood cardioplegia, furthermore to determine, whether or not RIPC is still operative during Off-pump coronary artery bypass surgery (OPCAB), finally to elucidate intra-cellular mechanisms involved in myocardial protection by RIPC and their possible systemic mediators.

Detailed description: Remote ischemic preconditioning (RIPC) protocol before CABG (study arm A) or OPCAB (study arm B) consists of 3 cycles of 5 minutes left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 minutes of reperfusion after induction of anesthesia before coronary artery bypass surgery. For myocardial molecular analyses, left ventricular biopsies are taken before induction of cardioplegic cardiac arrest (A) or first coronary incision (B), and 5 to 10 minutes after aortic unclamping during reperfusion of the myocardium (A) or 5 to 10 minutes after the completion of the last anastomosis (B). Blood samples are taken prior to RIPC and during the first three postoperative days.

Eligibility criteria: Inclusion Criteria:

* Confirmed triple vessel coronary artery disease
* Indication for surgical coronary revascularisation
* Written informed consent
* Age ≥ 18 years

Exclusion Criteria:

* Age \> 80 years
* Instable angina/acute coronary syndrome
* Emergency surgery
* Recent myocardial infarction within 7 days prior to surgery
* Recent major infection/sepsis within 7 days prior to surgery
* Significant hepatic, renal oder pulmonary disease
* Other concomitant surgical procedures

Primary outcomes:
measure: Perioperative extent of myocardial injury as measured by cardiac troponin T serum release over 72 hours after coronary bypass surgery and its area under the curve (AUC).
timeFrame: 72 hours postoperatively after CABG surgery
Secondary outcomes:
measure: All-cause mortality
timeFrame: 30 days and 1 year after coronary bypass surgery
measure: Major adverse cardiac and cerebrovascular events (MACCE)
timeFrame: 30 days and 1 year after coronary bypass surgery
measure: Myocardial infarction
timeFrame: 30 days and 1 year after coronary bypass surgery
measure: Renal function
timeFrame: 30 days and 1 year after coronary bypass surgery
measure: circulating microparticles after coronary bypass surgery
timeFrame: perioperatively, 3 months and 1 year after coronary bypass surgery
Other outcomes:
Locations:
city: Duesseldorf
country: Germany
facility: Dept. Cardiovascular Surgery, University Hospital, Heinrich Heine University
Study officials:
affiliation: Dept. of Cardiovascular Surgery, University Hospital, Heinrich Heine University, Duesseldorf, Germany
name: Payam Akhyari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept. of Cardiovascular Surgery, University Hospital, Heinrich Heine University, Duesseldorf, Germany
name: Alexander Albert, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept. of Cardiovascular Surgery, University Hospital, Heinrich Heine University, Duesseldorf, Germany
name: Artur Lichtenberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: nst. of Pathophysiology, University Duisburg-Essen, University Hospital Essen, Essen, Germany
name: Gerd Heusch, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hausenloy DJ, Erik Botker H, Condorelli G, Ferdinandy P, Garcia-Dorado D, Heusch G, Lecour S, van Laake LW, Madonna R, Ruiz-Meana M, Schulz R, Sluijter JP, Yellon DM, Ovize M. Translating cardioprotection for patient benefit: position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res. 2013 Apr 1;98(1):7-27. doi: 10.1093/cvr/cvt004. Epub 2013 Jan 19.
citation: Heusch G, Musiolik J, Kottenberg E, Peters J, Jakob H, Thielmann M. STAT5 activation and cardioprotection by remote ischemic preconditioning in humans: short communication. Circ Res. 2012 Jan 6;110(1):111-5. doi: 10.1161/CIRCRESAHA.111.259556. Epub 2011 Nov 23.