Effects of Remote Ischemic PreConditioning in Off-pump Versus On-pump Coronary Artery Bypass Grafting(RIPCON)

Myocardial Injury Clinical Trial

— RIPCON  

Official title:

Effects of Remote Ischemic PreConditioning in Off-pump Versus On-pump Coronary

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01608984
• Other study ID #: RIPCON-12
• Status: Recruiting
• Phase: Phase 1
• First received: May 29, 2012
• Last updated: July 15, 2013
• Start date: May 2012
• Est. completion date: December 2015

Study information

• Verified date: July 2013
• Source: Heinrich-Heine University, Duesseldorf
• Contact: Payam Akhyari, MD
• Phone: +492118118331
• Email: payam.akhyari[@]med.uni-duesseldorf.de
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Myocardial Injury

Intervention

Procedure:
• Remote ischemic preconditioning (RIPC)
3 cycles of 5 min left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 min reperfusion. The applied anesthesia protocol avoids the use of propofol. Drugs: isoflurane+sufentanil anesthesia Anaesthesia is maintained by inhaled isoflurane in concentrations 0.7-0.8 % end-tidal with additional sufentanil injected during surgery, as required. In the CABG-arms, during extracorporal circulation patients receive isoflurane via a vaporizer incorporated in the extracorporeal gas supply in the same concentrations.
• Coronary artery bypass grafting (CABG) without remote ischemic preconditioning protocol
The applied anesthesia protocol avoids the use of propofol. Drugs: isoflurane+sufentanil anesthesia Anaesthesia is maintained by inhaled isoflurane in concentrations 0.7-0.8 % end-tidal with additional sufentanil injected during surgery, as required. During extracorporal circulation patients receive isoflurane via a vaporizer incorporated in the extracorporeal gas supply in the same concentrations.
• Off-pump Coronary artery bypass surgery without remote ischemic preconditioning
The applied anesthesia protocol avoids the use of propofol. Drugs: isoflurane+sufentanil anesthesia Anaesthesia is maintained by inhaled isoflurane in concentrations 0.7-0.8 % end-tidal with additional sufentanil injected during surgery, as required.

Locations

Country	Name	City	State
Germany	Dept. Cardiovascular Surgery, University Hospital, Heinrich Heine University	Duesseldorf

Sponsors (2)

Lead Sponsor	Collaborator
Heinrich-Heine University, Duesseldorf	University Hospital, Essen

Country where clinical trial is conducted

Germany, 

References & Publications (2)

Hausenloy DJ, Erik Bøtker 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).		72 hours postoperatively after CABG surgery	Yes
Secondary	All-cause mortality		30 days and 1 year after coronary bypass surgery	Yes
Secondary	Major adverse cardiac and cerebrovascular events (MACCE)		30 days and 1 year after coronary bypass surgery	Yes
Secondary	Myocardial infarction		30 days and 1 year after coronary bypass surgery	Yes
Secondary	Renal function		30 days and 1 year after coronary bypass surgery	Yes
Secondary	circulating microparticles after coronary bypass surgery		perioperatively, 3 months and 1 year after coronary bypass surgery	No