Effect of Remote Ischemic Preconditioning on the Incidence of Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Graft Surgery

NCT ID: NCT02981680

Last Updated: 2017-10-24

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-30

Study Completion Date

2017-02-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Background:

Acute kidney injury (AKI) following coronary artery bypass graft (CABG) surgery is a major complication occurring in 1% to 53% of patients (depending on how it is defined) with the pooled rate of 18.2% and unfortunately 2.1% of them require renal replacement therapy. Cardiopulmonary bypass (CPB)-associated AKI increases mortality 2-4 fold regardless of AKI definition. It is also associated with increased risk of postoperative stroke, acute myocardial infarction, cardiac tamponade, heart failure, and lengthened intensive care unit and hospital stays. Even minor elevations of postoperative serum creatinine (SCr) have been associated with a significant increase in 30-day mortality, from a 3-fold increase risk for a small elevation of up to 0.5 mg/dL from baseline to an 18-fold increase risk of death with a SCr rise greater than 0.5 mg/dL.

The pathogenesis of CPB-associated AKI is complicated and includes hemodynamic, inflammatory and other mechanisms that interact at a cellular level. To date, despite several clinical trials of pharmacologic interventions, none of them have demonstrated conclusively efficacy in the prevention of AKI after cardiac surgery.

Remote ischemic preconditioning (RIPC) is a phenomenon in which brief ischemia of one organ or tissue, provokes a protective effect that can reduce the mass of infarction caused by vessel occlusion and reperfusion. In CABG surgery, cardiomyocyte injury caused by myocardial protection failure is predominantly responsible for adverse outcomes. RIPC was shown to reduce troponin release 24 h postoperatively in children undergoing corrective surgery for congenital heart disease. Other studies demonstrated that RIPC using brief ischemia and reperfusion of the upper limb reduces myocardial injury in adult patients undergoing CABG surgery.

Due to the similarities between the mechanisms of ischemia-reperfusion injury produced by RIPC and those proposed for AKI after CPB, we decided to test the hypothesis that RIPC prevents AKI in patients undergoing CABG surgery.

Methods:

180 patients who fulfill all inclusion and exclusion criteria will be divided into case and control groups (90 patients in the case and 90 patients in the control group).

Patients in the treatment group will receive three sequential sphygmomanometer cuff inflations on their right upper arm after induction of anesthesia in the operating room. The cuff will be inflated by the OR nurse up to 200 mmHg for five minutes each occasion, with five minutes deflation in between inflations. Following this pre-conditioning phase, surgery will be started. The entire pre-conditioning phase will last 30 minutes.

Patients in the control group will have the sphygmomanometer cuff placed on their right upper arm, but the cuff will not be inflated. Similar to patients in the treatment group, patients in the control group will undergo the same 30 minute delay before starting surgery.

Complete blood count (CBC), SCr, liver function test (LFT), will be checked before surgery.

After surgery, SCr will be checked daily. If AKI occurs, it will be managed and dialysis will be done if the patient requires it. All patients will undergo electrocardiogram and LFT after CABG surgery during hospital course.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Kidney Injury Coronary Artery Bypass Ischemic Preconditioning

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

remote ischemic preconditioning; transient limb ischemia; acute kidney injury; coronary artery bypass graft surgery

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

RIPC

Patients in the remote ischemic preconditioning (RIPC) group will receive three sequential sphygmomanometer cuff inflations on their right upper arm after induction of anesthesia in the operating room. The cuff will be inflated by the OR nurse up to 200 mmHg for five minutes each occasion, with five minutes deflation in between inflations. Following this pre-conditioning phase, surgery will be started. The entire pre-conditioning phase will last 30 minutes.

Group Type EXPERIMENTAL

Remote Ischemic Preconditioning (RIPC)

Intervention Type PROCEDURE

Remote ischemic preconditioning (RIPC) is a phenomenon in which brief ischemia of one organ or tissue, provokes a protective effect that can reduce the mass of infarction caused by vessel occlusion and reperfusion.

sham-RIPC

Patients in the sham-RIPC group will have the sphygmomanometer cuff placed on their right upper arm, but the cuff will not be inflated. Similar to patients in the RIPC group, patients in the sham-RIPC group will undergo the same 30 minute delay before starting surgery.

Group Type SHAM_COMPARATOR

sham-RIPC

Intervention Type PROCEDURE

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Remote Ischemic Preconditioning (RIPC)

Remote ischemic preconditioning (RIPC) is a phenomenon in which brief ischemia of one organ or tissue, provokes a protective effect that can reduce the mass of infarction caused by vessel occlusion and reperfusion.

Intervention Type PROCEDURE

sham-RIPC

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Candidate cardiac surgical patients
* Elective or urgent on pump coronary artery bypass grafting (CABG)
* Age 18 to 85 years
* Signed informed consent

Exclusion Criteria

* End-stage renal disease (receiving hemodialysis or glomerular filtration rate \<15 ml/min/1.73m2)
* Peripheral vascular disease
* Severe hepatic disease
* Planned off-pump surgery
* Pregnancy
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Shiraz University of Medical Sciences

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Sina Bagheri

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Mohammad Mahdi Sagheb, MD

Role: STUDY_CHAIR

Department of Nephrology, Shiraz University of Medical Sciences, Shiraz, Iran

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Shiraz University of Medical Sciences

Shiraz, Fars, Iran

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Iran

References

Explore related publications, articles, or registry entries linked to this study.

Pickering JW, James MT, Palmer SC. Acute kidney injury and prognosis after cardiopulmonary bypass: a meta-analysis of cohort studies. Am J Kidney Dis. 2015 Feb;65(2):283-93. doi: 10.1053/j.ajkd.2014.09.008. Epub 2014 Nov 5.

Reference Type BACKGROUND
PMID: 25445101 (View on PubMed)

Karkouti K, Wijeysundera DN, Yau TM, Callum JL, Cheng DC, Crowther M, Dupuis JY, Fremes SE, Kent B, Laflamme C, Lamy A, Legare JF, Mazer CD, McCluskey SA, Rubens FD, Sawchuk C, Beattie WS. Acute kidney injury after cardiac surgery: focus on modifiable risk factors. Circulation. 2009 Feb 3;119(4):495-502. doi: 10.1161/CIRCULATIONAHA.108.786913. Epub 2009 Jan 19.

Reference Type BACKGROUND
PMID: 19153273 (View on PubMed)

Gallagher S, Jones DA, Lovell MJ, Hassan S, Wragg A, Kapur A, Uppal R, Yaqoob MM. The impact of acute kidney injury on midterm outcomes after coronary artery bypass graft surgery: a matched propensity score analysis. J Thorac Cardiovasc Surg. 2014 Mar;147(3):989-95. doi: 10.1016/j.jtcvs.2013.03.016. Epub 2013 Apr 12.

Reference Type BACKGROUND
PMID: 23587469 (View on PubMed)

Ryden L, Ahnve S, Bell M, Hammar N, Ivert T, Holzmann MJ. Acute kidney injury following coronary artery bypass grafting: early mortality and postoperative complications. Scand Cardiovasc J. 2012 Apr;46(2):114-20. doi: 10.3109/14017431.2012.657229. Epub 2012 Feb 10.

Reference Type BACKGROUND
PMID: 22324648 (View on PubMed)

Mehta RH, Honeycutt E, Patel UD, Lopes RD, Shaw LK, Glower DD, Harrington RA, Califf RM, Sketch MH Jr. Impact of recovery of renal function on long-term mortality after coronary artery bypass grafting. Am J Cardiol. 2010 Dec 15;106(12):1728-34. doi: 10.1016/j.amjcard.2010.07.045. Epub 2010 Oct 26.

Reference Type BACKGROUND
PMID: 21126617 (View on PubMed)

Loef BG, Epema AH, Smilde TD, Henning RH, Ebels T, Navis G, Stegeman CA. Immediate postoperative renal function deterioration in cardiac surgical patients predicts in-hospital mortality and long-term survival. J Am Soc Nephrol. 2005 Jan;16(1):195-200. doi: 10.1681/ASN.2003100875. Epub 2004 Nov 24.

Reference Type BACKGROUND
PMID: 15563558 (View on PubMed)

Olsson D, Sartipy U, Braunschweig F, Holzmann MJ. Acute kidney injury following coronary artery bypass surgery and long-term risk of heart failure. Circ Heart Fail. 2013 Jan;6(1):83-90. doi: 10.1161/CIRCHEARTFAILURE.112.971705. Epub 2012 Dec 10.

Reference Type BACKGROUND
PMID: 23230310 (View on PubMed)

Dasta JF, Kane-Gill SL, Durtschi AJ, Pathak DS, Kellum JA. Costs and outcomes of acute kidney injury (AKI) following cardiac surgery. Nephrol Dial Transplant. 2008 Jun;23(6):1970-4. doi: 10.1093/ndt/gfm908. Epub 2008 Jan 4.

Reference Type BACKGROUND
PMID: 18178605 (View on PubMed)

Lassnigg A, Schmidlin D, Mouhieddine M, Bachmann LM, Druml W, Bauer P, Hiesmayr M. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol. 2004 Jun;15(6):1597-605. doi: 10.1097/01.asn.0000130340.93930.dd.

Reference Type BACKGROUND
PMID: 15153571 (View on PubMed)

Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol. 2006 Jan;1(1):19-32. doi: 10.2215/CJN.00240605. Epub 2005 Oct 19.

Reference Type BACKGROUND
PMID: 17699187 (View on PubMed)

Burns KE, Chu MW, Novick RJ, Fox SA, Gallo K, Martin CM, Stitt LW, Heidenheim AP, Myers ML, Moist L. Perioperative N-acetylcysteine to prevent renal dysfunction in high-risk patients undergoing cabg surgery: a randomized controlled trial. JAMA. 2005 Jul 20;294(3):342-50. doi: 10.1001/jama.294.3.342.

Reference Type BACKGROUND
PMID: 16030279 (View on PubMed)

Young EW, Diab A, Kirsh MM. Intravenous diltiazem and acute renal failure after cardiac operations. Ann Thorac Surg. 1998 May;65(5):1316-9. doi: 10.1016/s0003-4975(98)00157-x.

Reference Type BACKGROUND
PMID: 9594859 (View on PubMed)

Ranucci M, Soro G, Barzaghi N, Locatelli A, Giordano G, Vavassori A, Manzato A, Melchiorri C, Bove T, Juliano G, Uslenghi MF. Fenoldopam prophylaxis of postoperative acute renal failure in high-risk cardiac surgery patients. Ann Thorac Surg. 2004 Oct;78(4):1332-7; discussion 1337-8. doi: 10.1016/j.athoracsur.2004.02.065.

Reference Type BACKGROUND
PMID: 15464494 (View on PubMed)

Venugopal V, Ludman A, Yellon DM, Hausenloy DJ. 'Conditioning' the heart during surgery. Eur J Cardiothorac Surg. 2009 Jun;35(6):977-87. doi: 10.1016/j.ejcts.2009.02.014. Epub 2009 Mar 25.

Reference Type BACKGROUND
PMID: 19324569 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16750696 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17707752 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19508973 (View on PubMed)

Bonventre JV, Zuk A. Ischemic acute renal failure: an inflammatory disease? Kidney Int. 2004 Aug;66(2):480-5. doi: 10.1111/j.1523-1755.2004.761_2.x.

Reference Type BACKGROUND
PMID: 15253693 (View on PubMed)

Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007 Sep 13;357(11):1121-35. doi: 10.1056/NEJMra071667. No abstract available.

Reference Type BACKGROUND
PMID: 17855673 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

94-01-01-11214

Identifier Type: -

Identifier Source: org_study_id