Remote Ischemic Preconditioning in Coronary Artery Bypass Grafting With Cold Crystalloid Cardioplegic Arrest

NCT ID: NCT01406678

Last Updated: 2023-05-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

1204 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-07-31

Study Completion Date

2020-04-30

Brief Summary

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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

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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.

Conditions

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Myocardial Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

RIPC

Intervention Type PROCEDURE

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

isoflurane+sufentanil anesthesia

Intervention Type DRUG

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.

Control

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

Group Type PLACEBO_COMPARATOR

Control

Intervention Type PROCEDURE

Coronary artery bypass surgery without remote ischemic preconditioning protocol

isoflurane+sufentanil anesthesia

Intervention Type DRUG

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.

Interventions

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RIPC

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

Intervention Type PROCEDURE

Control

Coronary artery bypass surgery without remote ischemic preconditioning protocol

Intervention Type PROCEDURE

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.

Intervention Type DRUG

Other Intervention Names

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RIPC: Remote ischemic preconditioning CABG: Coronary artery bypass grafting Coronary artery bypass surgery Isoflurane, (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane), Forane Sufentanil, Sufenta, (R-30730)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Essen

OTHER

Sponsor Role lead

Responsible Party

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Matthias Thielmann

Matthias Thielman, MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Matthias Thielmann, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Thoracic and Cardiovascular Surgery, West-German Heart Center, University Duisburg-Essen, Essen, Germany

Eva Kottenberg, M.D., PhD.

Role: PRINCIPAL_INVESTIGATOR

Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen, Universitätsklinikum Essen, Essen, Germany

Gerd Heusch, M.D., PhD.

Role: PRINCIPAL_INVESTIGATOR

Institut für Pathophysiologie, Universität Duisburg-Essen, Universitätsklinikum Essen, Essen, Germany

Locations

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Department of Thoracic and Cardiovascular Surgery, West-German Heart Center, University Duisburg-Essen

Essen, , Germany

Site Status

Countries

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Germany

References

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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.

Reference Type RESULT
PMID: 20495811 (View on PubMed)

Zhang L, Zhou K, Gu T, Xu J, Shi M, Zhu J, Liu J. Cardiopulmonary Protection of Modified Remote Ischemic Preconditioning in Mitral Valve Replacement Surgery: A Randomized Controlled Trial. Cardiovasc Ther. 2024 Jun 24;2024:9889995. doi: 10.1155/2024/9889995. eCollection 2024.

Reference Type DERIVED
PMID: 39742012 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30548252 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24548338 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23953384 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23465551 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23440355 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22116817 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22103808 (View on PubMed)

Other Identifiers

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WDHZ-TC-0801

Identifier Type: -

Identifier Source: org_study_id

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