Effect of Remote Ischemic Preconditioning in Patient Undergoing Cardiac Bypass Surgery
Primary Purpose
Coronary Heart Disease
Status
Active
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Remote ischemic preconditioning
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Coronary Heart Disease focused on measuring Coronary artery bypass graft surgery, Remote ischemic preconditioning, Troponin-T
Eligibility Criteria
Inclusion Criteria:
- Adult patients undergoing elective CABG surgery
Exclusion Criteria:
- <18 years old
- Significant renal or hepatic disease
- Previous acute myocardial infarction (within 4 weeks)
Sites / Locations
- The UCLH Heart Hospital, 14-16 Westmoreland St.
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Remote preconditioning
Placebo
Arm Description
Simultaneous inflation (5min) and deflation (5min) of cuffs placed on upper arm and thigh - cycle repeated 2 times
Deflated cuffs placed on upperarm and thigh for 20 minutes
Outcomes
Primary Outcome Measures
Troponin-T release over the perioperative 72-hour period.
Secondary Outcome Measures
Full Information
NCT ID
NCT00397163
First Posted
November 6, 2006
Last Updated
November 3, 2020
Sponsor
University College London Hospitals
1. Study Identification
Unique Protocol Identification Number
NCT00397163
Brief Title
Effect of Remote Ischemic Preconditioning in Patient Undergoing Cardiac Bypass Surgery
Official Title
A Clinical Study Investigating Ischemic Preconditioning in Type II Diabetic Patients Undergoing Coronary Artery Bypass Graft Surgery.
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 2010 (undefined)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
November 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University College London Hospitals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
During coronary artery bypass graft surgery, injury occurs to the heart muscle. Some of this injury is due to the deprivation of oxygen and nutrients to the heart (a process called ischemia) during the surgery itself. The objective of this study is to examine whether remote ischaemic preconditioning (RIPC), in which the application of transient ischemia to the forearm and thigh (through the inflation of blood pressure cuffs placed on the right upper arm and upper thigh) may reduce the injury to the heart muscle sustained during cardiac surgery.
The study hypothesis is: remote ischemic preconditioning will protect the heart and improve short-term clinical outcomes during coronary artery bypass graft surgery.
Detailed Description
Ischemic heart disease (IHD) is currently the leading cause of morbidity and mortality in the developed world, and is set to become the leading cause of death in the world by the year 2020, according to the World Health Organisation. Patients with severe IHD that require coronary artery bypass graft (CABG) surgery, although protected by techniques such as cross-clamp fibrillation and cardioplegia, still sustain significant myocardial injury as evidenced by perioperative troponin T or I or CK-MB release. Novel treatment strategies are required to limit the myocardial injury sustained by patients undergoing CABG surgery in order to improve the clinical outcomes of this patient group.
One such cardioprotective strategy is remote ischemic preconditioning(RIPC) which describes the cardioprotection obtained from inducing ischemia in tissue or an organ remote from the heart. Our laboratory and others have established RIPC using forearm ischemia (induced by an automated cuff applied to the upper arm) as an effective cardioprotective intervention in children undergoing corrective cardiac surgery for congenital heart disease and in adults undergoing CABG surgery. In this study we investigate whether simultaneous inflation/deflation of cuffs placed on the upper arm and thigh can reduce peri-operative myocardial injury and improve short-term outcomes in patients undergoing CABG surgery.
Eligible patients will be those patients undergoing elective CABG surgery who are >18 years old, with no significant renal or hepatic disease, and have not had a recent AMI (within 1 month).
Consented patients will randomized to RIPC treatment or control.The RIPC protocol will comprise simultaneous 2 x 5 minutes of forearm and lower leg ischemia (with an automated pressure cuff inflated to 200 mmHg) with an intervening 5 minutes of reperfusion (during which the cuff is deflated) between each inflation. The control protocol will comprise a deflated cuff being placed on the upper arm and thigh for 20 minutes. The RIPC protocol will be implemented after the patients have been anesthetized and immediately prior to CABG surgery.
The measured endpoint of cardioprotection will be troponin-T release at 0, 12, 24, 48 and 72 hours following CABG surgery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Heart Disease
Keywords
Coronary artery bypass graft surgery, Remote ischemic preconditioning, Troponin-T
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
Participant
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Remote preconditioning
Arm Type
Active Comparator
Arm Description
Simultaneous inflation (5min) and deflation (5min) of cuffs placed on upper arm and thigh - cycle repeated 2 times
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Deflated cuffs placed on upperarm and thigh for 20 minutes
Intervention Type
Procedure
Intervention Name(s)
Remote ischemic preconditioning
Other Intervention Name(s)
Remote Ischaemic Preconditioning
Intervention Description
Blood pressure cuff inflation
Intervention Type
Procedure
Intervention Name(s)
Placebo
Other Intervention Name(s)
Control
Intervention Description
Deflated cuff on upper arm and thigh for 20 min
Primary Outcome Measure Information:
Title
Troponin-T release over the perioperative 72-hour period.
Time Frame
3 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients undergoing elective CABG surgery
Exclusion Criteria:
<18 years old
Significant renal or hepatic disease
Previous acute myocardial infarction (within 4 weeks)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Derek M Yellon, PhD DSc
Organizational Affiliation
The Hatter Cardiovascular Institute, UCL.
Official's Role
Principal Investigator
Facility Information:
Facility Name
The UCLH Heart Hospital, 14-16 Westmoreland St.
City
London
ZIP/Postal Code
W1G 8PH
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
16818489
Citation
Kharbanda RK, Li J, Konstantinov IE, Cheung MM, White PA, Frndova H, Stokoe J, Cox P, Vogel M, Van Arsdell G, MacAllister R, Redington AN. Remote ischaemic preconditioning protects against cardiopulmonary bypass-induced tissue injury: a preclinical study. Heart. 2006 Oct;92(10):1506-11. doi: 10.1136/hrt.2004.042366. Epub 2006 Jul 3.
Results Reference
background
PubMed Identifier
16053957
Citation
Loukogeorgakis SP, Panagiotidou AT, Broadhead MW, Donald A, Deanfield JE, MacAllister RJ. Remote ischemic preconditioning provides early and late protection against endothelial ischemia-reperfusion injury in humans: role of the autonomic nervous system. J Am Coll Cardiol. 2005 Aug 2;46(3):450-6. doi: 10.1016/j.jacc.2005.04.044.
Results Reference
background
PubMed Identifier
15466634
Citation
Broadhead MW, Kharbanda RK, Peters MJ, MacAllister RJ. KATP channel activation induces ischemic preconditioning of the endothelium in humans in vivo. Circulation. 2004 Oct 12;110(15):2077-82. doi: 10.1161/01.CIR.0000144304.91010.F0. Epub 2004 Oct 4.
Results Reference
background
PubMed Identifier
12460865
Citation
Kharbanda RK, Mortensen UM, White PA, Kristiansen SB, Schmidt MR, Hoschtitzky JA, Vogel M, Sorensen K, Redington AN, MacAllister R. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation. 2002 Dec 3;106(23):2881-3. doi: 10.1161/01.cir.0000043806.51912.9b.
Results Reference
background
PubMed Identifier
11273988
Citation
Kharbanda RK, Peters M, Walton B, Kattenhorn M, Mullen M, Klein N, Vallance P, Deanfield J, MacAllister R. Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo. Circulation. 2001 Mar 27;103(12):1624-30. doi: 10.1161/01.cir.103.12.1624.
Results Reference
background
PubMed Identifier
16750696
Citation
Cheung MM, Kharbanda RK, Konstantinov IE, Shimizu M, Frndova H, Li J, Holtby HM, Cox PN, Smallhorn JF, Van Arsdell GS, Redington AN. Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J Am Coll Cardiol. 2006 Jun 6;47(11):2277-82. doi: 10.1016/j.jacc.2006.01.066. Epub 2006 May 15.
Results Reference
background
PubMed Identifier
15973170
Citation
Konstantinov IE, Li J, Cheung MM, Shimizu M, Stokoe J, Kharbanda RK, Redington AN. Remote ischemic preconditioning of the recipient reduces myocardial ischemia-reperfusion injury of the denervated donor heart via a Katp channel-dependent mechanism. Transplantation. 2005 Jun 27;79(12):1691-5. doi: 10.1097/01.tp.0000159137.76400.5d.
Results Reference
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PubMed Identifier
15498829
Citation
Kristiansen SB, Henning O, Kharbanda RK, Nielsen-Kudsk JE, Schmidt MR, Redington AN, Nielsen TT, Botker HE. Remote preconditioning reduces ischemic injury in the explanted heart by a KATP channel-dependent mechanism. Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1252-6. doi: 10.1152/ajpheart.00207.2004. Epub 2004 Oct 21.
Results Reference
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PubMed Identifier
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Citation
Konstantinov IE, Arab S, Kharbanda RK, Li J, Cheung MM, Cherepanov V, Downey GP, Liu PP, Cukerman E, Coles JG, Redington AN. The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans. Physiol Genomics. 2004 Sep 16;19(1):143-50. doi: 10.1152/physiolgenomics.00046.2004. Epub 2004 Aug 10.
Results Reference
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PubMed Identifier
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Citation
Candilio L, Malik A, Ariti C, Barnard M, Di Salvo C, Lawrence D, Hayward M, Yap J, Roberts N, Sheikh A, Kolvekar S, Hausenloy DJ, Yellon DM. Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial. Heart. 2015 Feb;101(3):185-92. doi: 10.1136/heartjnl-2014-306178. Epub 2014 Sep 24.
Results Reference
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PubMed Identifier
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Citation
Venugopal V, Hausenloy DJ, Ludman A, Di Salvo C, Kolvekar S, Yap J, Lawrence D, Bognolo J, Yellon DM. Remote ischaemic preconditioning reduces myocardial injury in patients undergoing cardiac surgery with cold-blood cardioplegia: a randomised controlled trial. Heart. 2009 Oct;95(19):1567-71. doi: 10.1136/hrt.2008.155770. Epub 2009 Jun 8.
Results Reference
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PubMed Identifier
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Citation
Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S, Hayward M, Keogh B, MacAllister RJ, Yellon DM. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet. 2007 Aug 18;370(9587):575-9. doi: 10.1016/S0140-6736(07)61296-3.
Results Reference
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Effect of Remote Ischemic Preconditioning in Patient Undergoing Cardiac Bypass Surgery
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