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N-acetylcysteine to Prevent Renal Failure

Primary Purpose

Kidney Failure, Acute, Oxidative Stress Induction

Status
Unknown status
Phase
Not Applicable
Locations
Brazil
Study Type
Interventional
Intervention
N-acetylcysteine
Control
Sponsored by
Instituto do Coracao
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Kidney Failure, Acute focused on measuring N-acetylcysteine, Myocardial Revascularization, Acute Renal Failure, Oxidative Stress

Eligibility Criteria

30 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Instituto do CoracaoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

N-Acetylcysteine

Control

Arm Description

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.

This group will receive only the infusion of saline in the same doses and infusion rate.

Outcomes

Primary Outcome Measures

Decrease in glomerular filtration defined by at least 30% compared to preoperative levels .

Secondary Outcome Measures

Up 50% of preoperative levels of serum creatinine.
Death from any cause.
Need for dialysis
Cardiovascular morbidity.
Increased levels of Cystatin C.
Increased levels of NGAL.
Increased levels of isoprostane.

Full Information

First Posted
May 18, 2011
Last Updated
May 24, 2011
Sponsor
Instituto do Coracao
Collaborators
Fundação de Amparo à Pesquisa do Estado de São Paulo
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1. Study Identification

Unique Protocol Identification Number
NCT01359722
Brief Title
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

2. Study Status

Record Verification Date
October 2009
Overall Recruitment Status
Unknown status
Study Start Date
March 2010 (undefined)
Primary Completion Date
December 2011 (Anticipated)
Study Completion Date
December 2012 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
Instituto do Coracao
Collaborators
Fundação de Amparo à Pesquisa do Estado de São Paulo

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Failure, Acute, Oxidative Stress Induction
Keywords
N-acetylcysteine, Myocardial Revascularization, Acute Renal Failure, Oxidative Stress

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
N-Acetylcysteine
Arm Type
Experimental
Arm Description
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.
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
This group will receive only the infusion of saline in the same doses and infusion rate.
Intervention Type
Drug
Intervention Name(s)
N-acetylcysteine
Other Intervention Name(s)
Fluimucil
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Control
Other Intervention Name(s)
saline
Intervention Description
The control group will receive only the infusion of saline in the same doses and infusion rate.
Primary Outcome Measure Information:
Title
Decrease in glomerular filtration defined by at least 30% compared to preoperative levels .
Time Frame
Within the first 72 hours postoperatively
Secondary Outcome Measure Information:
Title
Up 50% of preoperative levels of serum creatinine.
Time Frame
Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Title
Death from any cause.
Time Frame
Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Title
Need for dialysis
Time Frame
Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Title
Cardiovascular morbidity.
Time Frame
Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Title
Increased levels of Cystatin C.
Time Frame
Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Title
Increased levels of NGAL.
Time Frame
Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Title
Increased levels of isoprostane.
Time Frame
Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jose Jayme G de Lima, phD
Phone
+5511-30695048
Email
eduesley.santos@incor.usp.br
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jose Jayme G de Lima, phD
Organizational Affiliation
Instito do Coracao-HCFMUSP
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto do Coracao
City
Sao Paulo
ZIP/Postal Code
05403-900
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jose Jayme G de Lima, phD
Phone
+5511-3069-5048
Email
eduesley.santos@incor.usp.br
First Name & Middle Initial & Last Name & Degree
Eduesley S Santos, RN

12. IPD Sharing Statement

Citations:
PubMed Identifier
9783643
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.
Results Reference
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PubMed Identifier
10900277
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.
Results Reference
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PubMed Identifier
12392825
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.
Results Reference
background
PubMed Identifier
11470263
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.
Results Reference
background
PubMed Identifier
12821233
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.
Results Reference
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N-acetylcysteine to Prevent Renal Failure

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