Clinical trial NCT01406678: Remote Ischemic Preconditioning in Coronary Artery Bypass Grafting With Cold Crystalloid Cardioplegic Arrest
Official title: Effect of Remote Ischemic Preconditioning in Patients Undergoing On-pump Coronary Artery Bypass Graft Surgery With Crystalloid Cardioplegic Arrest
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Myocardial Injury
Keywords: remote ischemic preconditioning
coronary artery bypass grafting
myocardial injury
Lead sponsor: University Hospital, Essen
Sponsor class: OTHER
First posted: 2011-08-01
Enrollment: 1204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Remote ischemic preconditioning (RIPC) with transient upper limb ischemia/reperfusion reduces myocardial injury in patients undergoing on-pump coronary artery bypass (CABG) surgery with cross-clamp fibrillation or blood cardioplegia for myocardial protection. The present study assesses protection of heart, brain and kidney by RIPC under crystalloid cardioplegic arrest. The study also addresses safety and clinical outcome.

Detailed description: Remote ischemic preconditioning (RIPC) protocol after induction of anesthesia and before skin incision 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. For myocardial molecular analyses, left ventricular biopsies are taken before induction of cardioplegic cardiac arrest and at 10 minutes after aortic unclamping during reperfusion of the myocardium.

Eligibility criteria: Inclusion Criteria:

* Consecutive patients \>18 years of age
* Double- or triple-vessel coronary artery disease
* Elective isolated first-time CABG
* Combined valve surgery + CABG
* Written informed consent

Exclusion Criteria:

* Renal failure (creatinine ≥ 200 µmol/L)
* Peripheral vascular disease affecting upper limbs
* Preoperative inotropic support
* Any kind of mechanical assist device
* Acute or recent (\<4 weeks) acute coronary syndromes
* Any PCI (\<6 weeks)
* Any reasons for preoperative cTnI elevation
* Emergency surgery
* Redo surgery

Primary outcomes:
measure: 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).
timeFrame: 72 hours postoperatively after CABG surgery
Secondary outcomes:
measure: All-cause mortality
timeFrame: 30 days and 1 year and complete follow-up after CABG surgery
measure: Major adverse cardiac and cerebrovascular events (MACCE)
timeFrame: at 30 days and 1 year and complete follow-up after CABG surgery
measure: Myocardial infarction
timeFrame: 30 days and 1 year and complete follow-up after CABG surgery
measure: Renal function
timeFrame: 72 hours post CABG
Other outcomes:
Locations:
city: Essen
country: Germany
facility: Department of Thoracic and Cardiovascular Surgery, West-German Heart Center, University Duisburg-Essen
Study officials:
affiliation: Department of Thoracic and Cardiovascular Surgery, West-German Heart Center, University Duisburg-Essen, Essen, Germany
name: Matthias Thielmann, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen, Universitätsklinikum Essen, Essen, Germany
name: Eva Kottenberg, M.D., PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut für Pathophysiologie, Universität Duisburg-Essen, Universitätsklinikum Essen, Essen, Germany
name: Gerd Heusch, M.D., PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1007/s00395-010-0104-5. Epub 2010 May 21.
citation: Frey UH, Klaassen M, Ochsenfarth C, Murke F, Thielmann M, Kottenberg E, Kleinbongard P, Klenke S, Engler A, Heusch G, Giebel B, Peters J. Remote ischaemic preconditioning increases serum extracellular vesicle concentrations with altered micro-RNA signature in CABG patients. Acta Anaesthesiol Scand. 2019 Apr;63(4):483-492. doi: 10.1111/aas.13296. Epub 2018 Dec 11.
citation: Kottenberg E, Thielmann M, Kleinbongard P, Frey UH, Heine T, Jakob H, Heusch G, Peters J. Myocardial protection by remote ischaemic pre-conditioning is abolished in sulphonylurea-treated diabetics undergoing coronary revascularisation. Acta Anaesthesiol Scand. 2014 Apr;58(4):453-62. doi: 10.1111/aas.12278. Epub 2014 Feb 18.
citation: Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, Price V, Tsagakis K, Neuhauser M, Peters J, Jakob H, Heusch G. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet. 2013 Aug 17;382(9892):597-604. doi: 10.1016/S0140-6736(13)61450-6.
citation: Kottenberg E, Musiolik J, Thielmann M, Jakob H, Peters J, Heusch G. Interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic preconditioning during coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2014 Jan;147(1):376-82. doi: 10.1016/j.jtcvs.2013.01.005. Epub 2013 Mar 1.
citation: Kleinbongard P, Thielmann M, Jakob H, Peters J, Heusch G, Kottenberg E. Nitroglycerin does not interfere with protection by remote ischemic preconditioning in patients with surgical coronary revascularization under isoflurane anesthesia. Cardiovasc Drugs Ther. 2013 Aug;27(4):359-61. doi: 10.1007/s10557-013-6451-3. No abstract available.
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.
citation: 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. doi: 10.1111/j.1399-6576.2011.02585.x. Epub 2011 Nov 21.