Back to results

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

Primary Purpose

Myocardial Injury

Status

Completed

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

RIPC

Control

isoflurane+sufentanil anesthesia

About this trial

This is an interventional treatment trial for Myocardial Injury focused on measuring remote ischemic preconditioning, coronary artery bypass grafting, myocardial injury

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

RIPC

Control

Arm 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.

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

Outcomes

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).

Secondary Outcome Measures

All-cause mortality

Major adverse cardiac and cerebrovascular events (MACCE)

Myocardial infarction

Renal function

Full Information

NCT ID

NCT01406678

First Posted

December 1, 2009

Last Updated

May 9, 2023

Sponsor

University Hospital, Essen

1. Study Identification

Unique Protocol Identification Number

NCT01406678

Brief Title

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

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Completed

Study Start Date

July 2008 (undefined)

Primary Completion Date

March 2018 (Actual)

Study Completion Date

April 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Hospital, Essen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myocardial Injury

Keywords

remote ischemic preconditioning, coronary artery bypass grafting, myocardial injury

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

InvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

1204 (Actual)

8. Arms, Groups, and Interventions

Arm Title

RIPC

Arm Type

Active Comparator

Arm Description

Arm Title

Control

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Procedure

Intervention Name(s)

RIPC

Other Intervention Name(s)

RIPC: Remote ischemic preconditioning, CABG: Coronary artery bypass grafting

Intervention Description

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

Intervention Name(s)

Control

Other Intervention Name(s)

Coronary artery bypass surgery

Intervention Description

Coronary artery bypass surgery without remote ischemic preconditioning protocol

Intervention Type

Drug

Intervention Name(s)

isoflurane+sufentanil anesthesia

Other Intervention Name(s)

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

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

All-cause mortality

Time Frame

30 days and 1 year and complete follow-up after CABG surgery

Title

Major adverse cardiac and cerebrovascular events (MACCE)

Time Frame

at 30 days and 1 year and complete follow-up after CABG surgery

Title

Myocardial infarction

Time Frame

30 days and 1 year and complete follow-up after CABG surgery

Title

Renal function

Time Frame

72 hours post CABG

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Matthias Thielmann, MD, PhD

Organizational Affiliation

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

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Eva Kottenberg, M.D., PhD.

Organizational Affiliation

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

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Gerd Heusch, M.D., PhD.

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Essen

ZIP/Postal Code

45122

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

20495811

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.

Results Reference

result

PubMed Identifier

30548252

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.

Results Reference

derived

PubMed Identifier

24548338

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.

Results Reference

derived

PubMed Identifier

23953384

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. Erratum In: Lancet. 2013 Sep 14;382(9896):940.

Results Reference

derived

PubMed Identifier

23465551

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.

Results Reference

derived

PubMed Identifier

23440355

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.

Results Reference

derived

PubMed Identifier

22116817

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.

Results Reference

derived

PubMed Identifier

22103808

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs