Clinical trial NCT01359722: N-acetylcysteine to Prevent Renal Failure
Official title: N-acetylcysteine to Prevent Renal Failure in Patients With Chronic Kidney Disease Undergoing Coronary Artery Bypass Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Kidney Failure, Acute
Oxidative Stress Induction
Keywords: N-acetylcysteine
Myocardial Revascularization
Acute Renal Failure
Oxidative Stress
Lead sponsor: Instituto do Coracao
Sponsor class: OTHER_GOV
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2011-05-25
Enrollment: 50
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Decrease in glomerular filtration defined by at least 30% compared to preoperative levels .
timeFrame: Within the first 72 hours postoperatively
Secondary outcomes:
measure: Up 50% of preoperative levels of serum creatinine.
timeFrame: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
measure: Death from any cause.
timeFrame: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
measure: Need for dialysis
timeFrame: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
measure: Cardiovascular morbidity.
timeFrame: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
measure: Increased levels of Cystatin C.
timeFrame: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
measure: Increased levels of NGAL.
timeFrame: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
measure: Increased levels of isoprostane.
timeFrame: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Instituto do Coracao
Study officials:
affiliation: Instito do Coracao-HCFMUSP
name: Jose Jayme G de Lima, phD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1177/000331979804900902.
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. doi: 10.1056/NEJM200007203430304.
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. doi: 10.1016/s0735-1097(02)02308-2.
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. doi: 10.1016/s0014-2999(01)01130-x.
citation: 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. doi: 10.1016/s0735-1097(03)00487-x.