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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Heinrich-Heine University, Duesseldorf
Sponsor:
Collaborator:
University Hospital, Essen
Information provided by (Responsible Party):
Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier:
NCT01608984
First received: May 29, 2012
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Myocardial Injury
Procedure: Remote ischemic preconditioning (RIPC)
Procedure: Coronary artery bypass grafting (CABG) without remote ischemic preconditioning protocol
Procedure: Off-pump Coronary artery bypass surgery without remote ischemic preconditioning
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Remote Ischemic PreConditioning in Off-pump Versus On-pump Coronary

Resource links provided by NLM:


Further study details as provided by Heinrich-Heine University, Duesseldorf:

Primary Outcome Measures:
  • 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). [ Time Frame: 72 hours postoperatively after CABG surgery ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • All-cause mortality [ Time Frame: 30 days and 1 year after coronary bypass surgery ] [ Designated as safety issue: Yes ]
  • Major adverse cardiac and cerebrovascular events (MACCE) [ Time Frame: 30 days and 1 year after coronary bypass surgery ] [ Designated as safety issue: Yes ]
  • Myocardial infarction [ Time Frame: 30 days and 1 year after coronary bypass surgery ] [ Designated as safety issue: Yes ]
  • Renal function [ Time Frame: 30 days and 1 year after coronary bypass surgery ] [ Designated as safety issue: Yes ]
  • circulating microparticles after coronary bypass surgery [ Time Frame: perioperatively, 3 months and 1 year after coronary bypass surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: May 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: RIPC-CABG
Remote ischemic preconditioning (RIPC) protocol before coronary artery bypass surgery with blood cardioplegia for cardiac arrest (CABG) 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 and 5 to 10 Minutes after aortic unclamping during reperfusion of the myocardium. Blood samples are taken up to 72 hours postoperatively.
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.

Other Names:
  • RIPC: remote ischemic preconditioning
  • CABG: coronary artery bypass grafting
  • OPCAB: Off-pump coronary artery bypass surgery
  • Isoflurane: 2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane, Forane
  • Sufentanil, Sufenta, (R-30730)
Placebo Comparator: Control-CABG
Control group: Coronary artery bypass grafting without RIPC protocol
Procedure: 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.
Active Comparator: RIPC-OPCAB
Remote ischemic preconditioning (RIPC) protocol before Off-pump coronary artery bypass surgery (OPCAB) 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 first coronary artery incision and 5 to 10 Minutes after completion of the coronary anastomoses. Blood samples are taken up to 72 hours postoperatively.
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.

Other Names:
  • RIPC: remote ischemic preconditioning
  • CABG: coronary artery bypass grafting
  • OPCAB: Off-pump coronary artery bypass surgery
  • Isoflurane: 2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane, Forane
  • Sufentanil, Sufenta, (R-30730)
Placebo Comparator: Control-OPCAB
Control group: Off-pump Coronary artery bypass surgery without RIPC protocol
Procedure: 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.

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01608984

Contacts
Contact: Payam Akhyari, MD +492118118331 payam.akhyari@med.uni-duesseldorf.de
Contact: Artur Lichtenberg, MD +492118118331 artur.lichtenberg@med.uni-duesseldorf.de

Locations
Germany
Dept. Cardiovascular Surgery, University Hospital, Heinrich Heine University Recruiting
Duesseldorf, Germany, 40225
Contact: Payam Akhyari, MD    +492118118331    payam.akhyari@med.uni-duesseldorf.de   
Contact: Alexander Albert, MD    +492118118331    alexander.albert@med.uni-duesseldorf.de   
Principal Investigator: Payam Akhyari, MD         
Principal Investigator: Alexander Albert, MD         
Sponsors and Collaborators
Heinrich-Heine University, Duesseldorf
University Hospital, Essen
Investigators
Principal Investigator: Payam Akhyari, MD Dept. of Cardiovascular Surgery, University Hospital, Heinrich Heine University, Duesseldorf, Germany
Principal Investigator: Alexander Albert, MD Dept. of Cardiovascular Surgery, University Hospital, Heinrich Heine University, Duesseldorf, Germany
Principal Investigator: Artur Lichtenberg, MD Dept. of Cardiovascular Surgery, University Hospital, Heinrich Heine University, Duesseldorf, Germany
Principal Investigator: Gerd Heusch, MD, PhD nst. of Pathophysiology, University Duisburg-Essen, University Hospital Essen, Essen, Germany
  More Information

Publications:
Responsible Party: Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier: NCT01608984     History of Changes
Other Study ID Numbers: RIPCON-12
Study First Received: May 29, 2012
Last Updated: July 15, 2013
Health Authority: Germany: Ethics Commission

Keywords provided by Heinrich-Heine University, Duesseldorf:
remote ischemic preconditioning
coronary artery bypass grafting
myocardial injury

Additional relevant MeSH terms:
Wounds and Injuries
Isoflurane
Sufentanil
Anesthetics, Inhalation
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Analgesics, Opioid
Narcotics
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Anesthetics, Intravenous

ClinicalTrials.gov processed this record on August 28, 2014