Remote Ischemic Preconditioning in Coronary Artery Bypass Grafting With Cold Crystalloid Cardioplegic Arrest - Full Text View

Sponsor:	University Hospital, Essen
Information provided by:	University Hospital, Essen
ClinicalTrials.gov Identifier:	NCT01406678

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 purpose of the present study is therefore to determine, whether or not RIPC is still operative when standard crystalloid cardioplegic arrest is used for myocardial protection.

Condition	Intervention	Phase
Myocardial Injury	Procedure: RIPC Procedure: Control Drug: isoflurane+sufentanil anesthesia Drug: propofol+sufentanil	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Effect of Remote Ischemic Preconditioning in Patients Undergoing On-pump Coronary Artery Bypass Graft Surgery With Crystalloid Cardioplegic Arrest

Resource links provided by NLM:

MedlinePlus related topics: Cardiac Arrest Coronary Artery Bypass Surgery

Drug Information available for: Propofol Isoflurane Sufentanil citrate

U.S. FDA Resources

Further study details as provided by University Hospital, Essen:

Primary Outcome Measures:

Perioperative extent of myocardial injury as measured by cardiac troponin I serum release over 72 hours after CABG 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 follow-up after CABG surgery ] [ Designated as safety issue: Yes ]
Major adverse cardiac and cerebrovascular events (MACCE) [ Time Frame: at 30 days and 1 year follow-up after CABG surgery ] [ Designated as safety issue: Yes ]
Myocardial infarction [ Time Frame: 30 days and 1 year follow-up after CABG surgery ] [ Designated as safety issue: Yes ]
Renal function [ Time Frame: 30 days and 1 year follow-up after CABG surgery ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	250
Study Start Date:	July 2008
Estimated Study Completion Date:	July 2013
Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: RIPC Remote ischemic preconditioning (RIPC) protocol before coronary artery bypass surgery 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 and 10 Minutes after aortic unclamping during reperfusion of the myocardium.	Procedure: RIPC 3 cycles of 5 min left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 min reperfusion Other Names: RIPC: Remote ischemic preconditioning CABG: Coronary artery bypass grafting Drug: 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. Other Names: Isoflurane, (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane), Forane Sufentanil, Sufenta, (R-30730) Drug: propofol+sufentanil Anaesthesia is maintained by continuous propofol infusion (0.07 - 0.15 mg/kg/min), with additional sufentanil injected during surgery, as required. During extracorporal circulation patients receive continuous propofol infusion. Other Name: propofol, diprivan, disoprivan, sufentanil, sufenta
Placebo Comparator: Control Control group: Coronary artery bypass surgery without remote ischemic preconditioning protocol	Procedure: Control Coronary artery bypass surgery without remote ischemic preconditioning protocol Other Name: Coronary artery bypass surgery Drug: 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. Other Names: Isoflurane, (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane), Forane Sufentanil, Sufenta, (R-30730) Drug: propofol+sufentanil Anaesthesia is maintained by continuous propofol infusion (0.07 - 0.15 mg/kg/min), with additional sufentanil injected during surgery, as required. During extracorporal circulation patients receive continuous propofol infusion. Other Name: propofol, diprivan, disoprivan, sufentanil, sufenta

Arms

Assigned Interventions

Active Comparator: RIPC

Remote ischemic preconditioning (RIPC) protocol before coronary artery bypass surgery 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 and 10 Minutes after aortic unclamping during reperfusion of the myocardium.

Procedure: RIPC

3 cycles of 5 min left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 min reperfusion

Other Names:

RIPC: Remote ischemic preconditioning
CABG: Coronary artery bypass grafting

Drug: 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.

Other Names:

Isoflurane, (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane), Forane
Sufentanil, Sufenta, (R-30730)

Drug: propofol+sufentanil

Anaesthesia is maintained by continuous propofol infusion (0.07 - 0.15 mg/kg/min), with additional sufentanil injected during surgery, as required. During extracorporal circulation patients receive continuous propofol infusion.

Other Name: propofol, diprivan, disoprivan, sufentanil, sufenta

Placebo Comparator: Control

Control group: Coronary artery bypass surgery without remote ischemic preconditioning protocol

Procedure: Control

Coronary artery bypass surgery without remote ischemic preconditioning protocol

Other Name: Coronary artery bypass surgery

Drug: 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.

Other Names:

Isoflurane, (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane), Forane
Sufentanil, Sufenta, (R-30730)

Drug: propofol+sufentanil

Anaesthesia is maintained by continuous propofol infusion (0.07 - 0.15 mg/kg/min), with additional sufentanil injected during surgery, as required. During extracorporal circulation patients receive continuous propofol infusion.

Other Name: propofol, diprivan, disoprivan, sufentanil, sufenta

Detailed Description:

Remote ischemic preconditioning (RIPC) protocol before coronary artery bypass surgery 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 and 10 Minutes after aortic unclamping during reperfusion of the myocardium.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Consecutive patients >18 years of age
Triple-vessel coronary artery disease
Non-diabetic
Elective isolated first-time CABG
Written informed consent

Exclusion Criteria:

Diabetes mellitus
Anti-diabetic medications
Renal failure (creatinine ≥ 200 µmol/L)
Peripheral vascular disease affecting upper limbs
Unstable angina
Preoperative inotropic support
Any kind of mechanical assist device
Acute or recent (<2 weeks) myocardial infarction
Any reasons for preoperative cTnI elevation
Emergency surgery
Combined surgery
Redo surgery

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01406678

Contacts

Contact: Matthias Thielmann, MD, PhD

+49-723-84908

matthias.thielmann@uni-due.de

Locations

Germany
Department of Thoracic and Cardiovascular Surgery, West-German Heart Center, University Duisburg-Essen	Recruiting
Essen, Germany, 45122
Contact: Matthias Thielmann, MD, PhD +49-201-723-84908 matthias.thielmann@uni-due.de
Principal Investigator: Matthias Thielmann, MD., PhD.

Sponsors and Collaborators

University Hospital, Essen

Investigators

Principal Investigator:	Matthias Thielmann, MD, PhD	Department of Thoracic and Cardiovascular Surgery, West-German Heart Center, University Duisburg-Essen, Essen, Germany
Principal Investigator:	Eva Kottenberg, M.D., PhD.	Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen, Universitätsklinikum Essen, Essen, Germany
Principal Investigator:	Gerd Heusch, M.D., PhD.	Institut für Pathophysiologie, Universität Duisburg-Essen, Universitätsklinikum Essen, Essen, Germany

More Information

Publications:

Thielmann M, Kottenberg E, Boengler K, Raffelsieper C, Neuhaeuser M, Peters J, Jakob H, Heusch G. Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest. Basic Res Cardiol. 2010 Sep;105(5):657-64. Epub 2010 May 21.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2011 Nov 23.

Kottenberg E, Thielmann M, Bergmann L, Heine T, Jakob H, Heusch G, Peters J. Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol - a clinical trial. Acta Anaesthesiol Scand. 2012 Jan;56(1):30-8. Epub 2011 Nov 21.

Responsible Party:	Matthias Thielman, MD, PhD, Department of Thoracic and Cardiovascular Surgery, West-German Heart Center Essen, University Hospital Essen, Essen, Germany
ClinicalTrials.gov Identifier:	NCT01406678 History of Changes
Other Study ID Numbers:	WDHZ-TC-0801
Study First Received:	December 1, 2009
Last Updated:	August 3, 2011
Health Authority:	Germany: Ethics Commission, University of Duisburg-Essen

Keywords provided by University Hospital, Essen:

remote ischemic preconditioning
coronary artery bypass grafting
myocardial injury

Additional relevant MeSH terms:

Anesthetics
Isoflurane
Propofol
Sufentanil
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Inhalation

Anesthetics, General
Anesthetics, Intravenous
Hypnotics and Sedatives
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Narcotics

ClinicalTrials.gov processed this record on May 23, 2012