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

Acute Kidney Injury Clinical Trial

Official title:

Effect of Remote Ischemic Preconditioning on the Incidence of Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Graft Surgery: A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02981680
• Other study ID #: 94-01-01-11214
• Status: Completed
• Phase: N/A
• First received: November 28, 2016
• Last updated: October 21, 2017
• Start date: November 2013
• Est. completion date: February 2017

Study information

• Verified date: October 2017
• Source: Shiraz University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Coronary Artery Bypass
• Ischemia
• Ischemic Preconditioning
• Wounds and Injuries

Intervention

Procedure:
• 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.
• sham-RIPC

Locations

Country	Name	City	State
Iran, Islamic Republic of	Shiraz University of Medical Sciences	Shiraz	Fars

Sponsors (1)

Lead Sponsor	Collaborator
Shiraz University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

References & Publications (19)

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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. — View 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. Epub 2006 May 15. — View Citation

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. — View Citation

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. — View Citation

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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. — View Citation

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* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of postoperative acute kidney injury (AKI)	Defined as an elevation of serum creatinine of =0.3 mg/dl or =50% within 72 hours after surgery	Within the first 72 hours after surgery
Secondary	Duration of hospital stay		Through hospital stay after surgery, an average of 5 days
Secondary	Duration of ICU stay		Through ICU stay, an average of 3 days
Secondary	All cause mortality		Through hospital stay after surgery, an average of 5 days
Secondary	Number of participants requiring dialysis		Through hospital stay after surgery, an average of 5 days
Secondary	Postoperative liver function	By measuring serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), and albumin	Preoperatively and at 24 h post-surgery
Secondary	Incidence of postoperative atrial fibrillation (AF)	Defined as the incidence of new-onset AF lasting for five minutes or longer	Within the first 72 hours after surgery
Secondary	Incidence of postoperative stroke	Defined as a new ischemic or hemorrhagic cerebrovascular accident with neurological deficit lasting >24 h	Through hospital stay after surgery, an average of 5 days