Perioperative Use of NAC to Prevent AKI in Patients With Pre-existing Moderate Renal Insufficiency Following Cardiac Surgery

Kidney Injury, Acute Clinical Trial

Official title:

Perioperative Use of N-acetylcysteine to Prevent Acute Kidney Injury in Patients With Pre-existing Moderate Renal Insufficiency Following Cardiac Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05555511
• Other study ID #: FMASU R 122/2022
• Status: Recruiting
• Phase: N/A
• Start date: August 26, 2022
• Est. completion date: February 26, 2023

Study information

• Verified date: December 2022
• Source: Ain Shams University
• Contact: Mohamed A. Alhadidy, MD
• Phone: 00201005092648
• Email: Mohamed_alaaeldin[@]med.asu.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Acute kidney injury (AKI) or renal impairment is an established complication of cardiac surgery occurring with an incidence up to 30%, To date, no agent has conferred renal protection. Considerable interest has developed in the potential for Nacetylcysteine (NAC) to exert a renoprotective effect in patients undergoing cardiac surgery. Due to the beneficial effect of NAC on contrast nephropathy and its reported anti-inflammatory effects.

Description:

Acute kidney injury (AKI), is a well-known complication of cardiac surgery, with an incidence of up to 30% depending on the definition. AKI caused by cardiac surgery is the second most common cause of AKI in the intensive care unit and is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB).

The pathogenesis of AKI after CPB is multifactorial, and is mostly due to hypo perfusion, reperfusion injury, activation of the systemic inflammatory response, and/or low cardiac output. Reperfusion will result in the formation of reactive oxygen species, resulting in injury to tissues.

The activation of the systemic inflammatory response is mostly due to the exposure of blood to the extracorporeal CPB circuit, resulting in the activation of the immune system, which is also mediated by the generation of reactive oxygen species. This results in increased recruitment of neutrophils, macrophages, and lymphocytes into the renal parenchyma, leading to AKI.

N-acetylcysteine (NAC) is well known for its antioxidant and free-radical scavenging properties, as well as its vasodilator properties. Its antioxidant properties enable it to prevent ischemic cell death, and as a free-radical scavenger, NAC mitigates the effect of increased reactive oxygen species caused by reperfusion. Hence, theoretically, NAC is able to counteract several mechanisms of kidney injury during cardiac surgery, namely, the systemic inflammatory response, free-radical injury, and ischemia.

In this study, we aimed to investigate if the perioperative use of acetylcysteine will prevent kidney injury after cardiac surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: February 26, 2023
• Est. primary completion date: January 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Scheduled for open heart Surgery with cardiopulmonary bypass (CPB) pump.

• Pre-existing moderate renal insufficiency serum creatinine more than 1.5 mg/dL

Exclusion Criteria:

• Patients on hemodialysis preoperatively

• History of renal transplantation

• IV contrast within 4 days prior to surgery

• Urgent/emergent surgery

• Preoperative hemodynamic instability (intra-aortic balloon pump support or vasoactive medications)

• Planned off-pump surgery;

• Planned deep-hypothermic-circulatory-arrest

• known or suspected allergy to NAC

• Patient Refusal.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Kidney Injury, Acute
• Renal Insufficiency

Intervention

Other:
• Control Group
Patients will not receive N-Acetylcystiene and will receive standard care according to our institutional protocol

Locations

Country	Name	City	State
Egypt	Cardiothoracic Academy, Ain Shams University Hospitals	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

References & Publications (9)

Ates B, Abraham L, Ercal N. Antioxidant and free radical scavenging properties of N-acetylcysteine amide (NACA) and comparison with N-acetylcysteine (NAC). Free Radic Res. 2008 Apr;42(4):372-7. doi: 10.1080/10715760801998638. — View Citation

Dexter F. Duration of cardiopulmonary bypass and outcome. J Cardiothorac Vasc Anesth. 2012 Apr;26(2):e19; author reply e19-20. doi: 10.1053/j.jvca.2011.12.012. Epub 2012 Jan 29. No abstract available. — View Citation

Diaz-Sandoval LJ, Kosowsky BD, Losordo DW. Acetylcysteine to prevent angiography-related renal tissue injury (the APART trial). Am J Cardiol. 2002 Feb 1;89(3):356-8. doi: 10.1016/s0002-9149(01)02243-3. No abstract available. — View Citation

Kotlyar E, Keogh AM, Thavapalachandran S, Allada CS, Sharp J, Dias L, Muller D. Prehydration alone is sufficient to prevent contrast-induced nephropathy after day-only angiography procedures--a randomised controlled trial. Heart Lung Circ. 2005 Dec;14(4):245-51. doi: 10.1016/j.hlc.2005.06.007. Epub 2005 Oct 3. — View Citation

Lee SH, Kim SJ, Kim HJ, Son JS, Lee R, Yoon TG. Acute Kidney Injury Following Cardiopulmonary Bypass in Children - Risk Factors and Outcomes. Circ J. 2017 Sep 25;81(10):1522-1527. doi: 10.1253/circj.CJ-17-0075. Epub 2017 May 17. — View Citation

Nadim MK, Forni LG, Bihorac A, Hobson C, Koyner JL, Shaw A, Arnaoutakis GJ, Ding X, Engelman DT, Gasparovic H, Gasparovic V, Herzog CA, Kashani K, Katz N, Liu KD, Mehta RL, Ostermann M, Pannu N, Pickkers P, Price S, Ricci Z, Rich JB, Sajja LR, Weaver FA, Zarbock A, Ronco C, Kellum JA. Cardiac and Vascular Surgery-Associated Acute Kidney Injury: The 20th International Consensus Conference of the ADQI (Acute Disease Quality Initiative) Group. J Am Heart Assoc. 2018 Jun 1;7(11):e008834. doi: 10.1161/JAHA.118.008834. No abstract available. — View Citation

Nigwekar SU, Kandula P. N-acetylcysteine in cardiovascular-surgery-associated renal failure: a meta-analysis. Ann Thorac Surg. 2009 Jan;87(1):139-47. doi: 10.1016/j.athoracsur.2008.09.026. — View Citation

Savluk OF, Guzelmeric F, Yavuz Y, Cevirme D, Gurcu E, Ogus H, Orki T, Kocak T. N-acetylcysteine versus Dopamine to Prevent Acute Kidney Injury after Cardiac Surgery in Patients with Preexisting Moderate Renal Insufficiency. Braz J Cardiovasc Surg. 2017 Jan-Feb;32(1):8-14. doi: 10.21470/1678-9741-2016-0028. — View Citation

Schopka S, Diez C, Camboni D, Floerchinger B, Schmid C, Hilker M. Impact of cardiopulmonary bypass on acute kidney injury following coronary artery bypass grafting: a matched pair analysis. J Cardiothorac Surg. 2014 Jan 18;9:20. doi: 10.1186/1749-8090-9-20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum Creatinine rise	Creatinine increase >25% or = 0.5 mg/dl above baseline	7days
Secondary	RRT	Need for Renal Replacement Therapy	7 days
Secondary	Length of ICU stay	Length of stay in the ICU in days	3 days
Secondary	Length of hospital stay	Length of stay in hospital in days	7 to 10 Days
Secondary	Mortality	Mortality rate	30 days
Secondary	Adverse effects	Occurrence of NAC adverse effects as (bronchospasm, urticaria, facial edema, nausea/vomiting).	2 days