NCT01406678

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,204

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jul 2008

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2008

Completed
1.4 years until next milestone

First Submitted

Initial submission to the registry

December 1, 2009

Completed
1.7 years until next milestone

First Posted

Study publicly available on registry

August 1, 2011

Completed
6.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2018

Completed
2.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2020

Completed
Last Updated

May 10, 2023

Status Verified

May 1, 2023

Enrollment Period

9.7 years

First QC Date

December 1, 2009

Last Update Submit

May 9, 2023

Conditions

Myocardial Injury

Keywords

remote ischemic preconditioningcoronary artery bypass graftingmyocardial injury

Outcome Measures

Primary Outcomes (1)

  • 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).

    72 hours postoperatively after CABG surgery

Secondary Outcomes (4)

  • All-cause mortality

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

  • Major adverse cardiac and cerebrovascular events (MACCE)

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

  • Myocardial infarction

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

  • Renal function

    72 hours post CABG

Study Arms (2)

RIPC

ACTIVE COMPARATOR

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: RIPCDrug: isoflurane+sufentanil anesthesia

Control

PLACEBO COMPARATOR

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

Procedure: ControlDrug: isoflurane+sufentanil anesthesia

Interventions

RIPCPROCEDURE

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

Also known as: RIPC: Remote ischemic preconditioning, CABG: Coronary artery bypass grafting
RIPC
ControlPROCEDURE

Coronary artery bypass surgery without remote ischemic preconditioning protocol

Also known as: Coronary artery bypass surgery
Control
isoflurane+sufentanil anesthesiaDRUG

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.

Also known as: Isoflurane, (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane), Forane, Sufentanil, Sufenta, (R-30730)
ControlRIPC

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

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

Essen, 45122, Germany

Location

Related Publications (9)

  • 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.

    PMID: 20495811RESULT

  • 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.

    PMID: 39742012DERIVED

  • 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.

    PMID: 30548252DERIVED

  • 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.

    PMID: 24548338DERIVED

  • 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.

    PMID: 23953384DERIVED

  • 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.

    PMID: 23465551DERIVED

  • 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.

    PMID: 23440355DERIVED

  • 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.

    PMID: 22116817DERIVED

  • 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.

    PMID: 22103808DERIVED

MeSH Terms

Interventions

Coronary Artery BypassIsofluraneSufentanil

Intervention Hierarchy (Ancestors)

Myocardial RevascularizationCardiac Surgical ProceduresCardiovascular Surgical ProceduresSurgical Procedures, OperativeVascular GraftingVascular Surgical ProceduresThoracic Surgical ProceduresMethyl EthersEthersOrganic ChemicalsFentanylPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Matthias Thielman, MD, PhD

Study Record Dates

First Submitted

December 1, 2009

First Posted

August 1, 2011

Study Start

July 1, 2008

Primary Completion

March 1, 2018

Study Completion

April 1, 2020

Last Updated

May 10, 2023

Record last verified: 2023-05

Locations

DE(1)