N-acetylcysteine to Prevent Renal Failure

Kidney Failure, Acute Clinical Trial

Official title:

N-acetylcysteine to Prevent Renal Failure in Patients With Chronic Kidney Disease Undergoing Coronary Artery Bypass Surgery

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT01359722
• Other study ID #: 0992/09
• Status: Unknown status
• Phase: N/A
• First received: May 18, 2011
• Last updated: May 24, 2011
• Start date: March 2010
• Est. completion date: December 2012

Study information

• Verified date: October 2009
• Source: Instituto do Coracao
• Contact: Jose Jayme G de Lima, phD
• Phone: +5511-30695048
• Email: eduesley.santos[@]incor.usp.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the possible effect nephroprotective of N-acetylcysteine in patients with chronic kidney disease undergoing elective coronary artery bypass grafting by serial evaluation of renal function and to evaluate whether treatment reduces cardiac mortality, cardiac events and Global mortality, if it interferes with oxidative stress and inflammation and the need for dialysis.

Description:

Renal failure is a serious and relatively frequent complication of cardiac surgery was observed, especially in diabetics and those with pre-existing renal dysfunction. Given that oxidative stress is elevated in diabetics and in renal and heart, it is reasonable to speculate on its involvement in the pathophysiology of this complication. It is unknown whether the incidence of postoperative renal failure can be reduced by antioxidants. N-acetylcysteine (NAC) is an antioxidant that prevents nephropathy induced by contrast medium and aminoglycosides and increases intracellular levels of cyclic guanosine monophosphate, acting as a vasodilator and platelet inhibitor.

Based on a knowledge of the pathophysiology of ARF, several interventions have been attempted over the past decades. However, various measures employed successfully in the prevention of experimental ARF did not result in success in clinical practice. Much of this failure is probably due to the difference between the experimental models of ARF that encountered in the clinic. Other factors that should be considered, and that may explain the poor results in clinical trials are: the time of use of the drug, dosage and route of administration, are not always adequate.

From the data in the literature, it remains doubtful whether the protective role of NAC is limited only to contrast nephropathy or whether it could have application in other clinical situations in which oxidative stress and vasoconstriction are determinants of injury, as occurs, for example, in CABG surgeries.

NAC is a drug of low cost and low toxicity, this paper intend to assess its role as prophylaxis of renal dysfunction in the postoperative period of CABG in patients with chronic kidney disease stages 3 and 4 (GFR between 15 and 59 mL/min/1, 73 m2 of body surface).

Recruitment information / eligibility

• Status: Unknown status
• Enrollment: 50
• Est. completion date: December 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

• adult patients aged 30 to 80 years old of both sexes

• indicated for elective CABG

• with glomerular filtration rate, assessed with the MDRD <60 mL/min/1, 73 m2 and> 15 mL / min / 1.73 m2 body surface

Exclusion Criteria:

• patients on chronic dialysis or with creatinine> 5 mg / dL preoperatively; individuals allergic or intolerant to N-acetylcysteine

• pregnant women

• patients with cancer

• patients underwent re-surgery within the first 72 hours postoperatively

Related Conditions & MeSH terms

• Acute Kidney Injury
• Kidney Failure, Acute
• Oxidative Stress Induction
• Renal Insufficiency

Intervention

Drug:
• N-acetylcysteine
N-acetylcysteine is administered at a dose of 150mg/kg in 500mL of saline EV in 1 hour followed by a dose of 50mg/kg in 500 mL of saline IV within 6 hours, beginning the infusion together to surgery.
• Control
The control group will receive only the infusion of saline in the same doses and infusion rate.

Locations

Country	Name	City	State
Brazil	Instituto do Coracao	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
Instituto do Coracao	Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (5)

Baker CS, Wragg A, Kumar S, De Palma R, Baker LR, Knight CJ. A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study. J Am Coll Cardiol. 2003 Jun 18;41(12):2114-8. — View Citation

Mazzon E, Britti D, De Sarro A, Caputi AP, Cuzzocrea S. Effect of N-acetylcysteine on gentamicin-mediated nephropathy in rats. Eur J Pharmacol. 2001 Jul 13;424(1):75-83. — View Citation

Shyu KG, Cheng JJ, Kuan P. Acetylcysteine protects against acute renal damage in patients with abnormal renal function undergoing a coronary procedure. J Am Coll Cardiol. 2002 Oct 16;40(8):1383-8. — View Citation

Suen WS, Mok CK, Chiu SW, Cheung KL, Lee WT, Cheung D, Das SR, He GW. Risk factors for development of acute renal failure (ARF) requiring dialysis in patients undergoing cardiac surgery. Angiology. 1998 Oct;49(10):789-800. — View Citation

Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000 Jul 20;343(3):180-4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Decrease in glomerular filtration defined by at least 30% compared to preoperative levels .		Within the first 72 hours postoperatively
Secondary	Up 50% of preoperative levels of serum creatinine.		Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Secondary	Death from any cause.		Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Secondary	Need for dialysis		Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Secondary	Cardiovascular morbidity.		Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Secondary	Increased levels of Cystatin C.		Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Secondary	Increased levels of NGAL.		Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Secondary	Increased levels of isoprostane.		Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.