Clinical trial NCT05555511: Perioperative Use of NAC to Prevent AKI in Patients With Pre-existing Moderate Renal Insufficiency Following Cardiac Surgery
Official title: Perioperative Use of N-acetylcysteine to Prevent Acute Kidney Injury in Patients With Pre-existing Moderate Renal Insufficiency Following Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Kidney Injury, Acute
Keywords: N-acetylcysteine
Acute kidney injury
Cardiac surgery
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2022-09-27
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized using computer generated random series into two groups according to the used drug into:

Group A: N-acetylcysteine group (23 Patients) Patients will receive N-acetylcysteine 600 mg intravenous(IV) every 12 hours 24 hours before surgery and will be continued for 48 hours after surgery.

Group B : Standard (control) group (23 Patients) Patients will not receive N-Acetylcysteine and will receive standard care according to our institutional protocol.
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Serum Creatinine rise
timeFrame: 7days
Secondary outcomes:
measure: RRT
timeFrame: 7 days
measure: Length of ICU stay
timeFrame: 3 days
measure: Length of hospital stay
timeFrame: 7 to 10 Days
measure: Mortality
timeFrame: 30 days
measure: Adverse effects
timeFrame: 2 days
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Cardiothoracic Academy, Ain Shams University Hospitals
Study officials:
affiliation: Ain Shams University
name: Mohamed A. Alhadidy
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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citation: 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.
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.
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.
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.
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.