Kidney Failure, AcuteNCT01359722
N-acetylcysteine to Prevent Renal Failure
A study testing N-acetylcysteine in people with Kidney Failure, Acute and Oxidative Stress Induction, run by Instituto do Coracao at 1 site in Brazil.
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… Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Kidney Failure, Acute, Oxidative Stress Induction
- What is being tested?
- N-acetylcysteine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteBrazil
- Study dates
- Mar 2010to Dec 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Instituto do Coracao
São Paulo, São Paulo, 05403-900
Jose Jayme G de Lima, phD, +5511-3069-5048, eduesley.santos@incor.usp.br
Eduesley S Santos, RN
About this study
Official title: N-acetylcysteine to Prevent Renal Failure in Patients With Chronic Kidney Disease Undergoing Coronary Artery Bypass Surgery
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.
Read the 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).
- Conditions
- Kidney Failure, Acute, Oxidative Stress Induction
- Being tested
- N-acetylcysteine, Control
- Keywords
- N-acetylcysteine, Myocardial Revascularization, Acute Renal Failure, Oxidative Stress
- Medical subject headings
- Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Also called Fluimucil
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.
ControlDrug
Also called saline
The control group will receive only the infusion of saline in the same doses and infusion rate.
| Study group | Role | What they receive |
|---|---|---|
| N-Acetylcysteine | Experimental | 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. Receives: Drug: N-acetylcysteine |
| Control | Placebo comparator | This group will receive only the infusion of saline in the same doses and infusion rate. Receives: Drug: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decrease in glomerular filtration defined by at least 30% compared to preoperative levels .
Measured: Within the first 72 hours postoperatively
Secondary outcomes (7)
Up 50% of preoperative levels of serum creatinine.
Measured: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Death from any cause.
Measured: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Need for dialysis
Measured: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Cardiovascular morbidity.
Measured: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Increased levels of Cystatin C.
Measured: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Increased levels of NGAL.
Measured: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Increased levels of isoprostane.
Measured: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2011 (estimated)
- Study startMar 2010
- Primary completionDec 2011 (estimated)
- Study completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Kidney Failure, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto do Coracao
- Sponsor type
- Other government
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Investigators
- Jose Jayme G de Lima, phD, Principal investigator, Instito do Coracao-HCFMUSP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01359722
- Sponsor's protocol ID
- 0992/09
- Status last verified
- Oct 2009
- First submitted
- 18 May 2011
- Last updated
- 25 May 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 9783643Tepel 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.
PubMed 10900277Shyu 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.
PubMed 12392825Mazzon 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.
PubMed 11470263Baker 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.
PubMed 12821233
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- N-acetylcysteine to Prevent Renal Failure in Patients With Chronic Kidney Disease Undergoing Coronary Artery Bypass Surgery
- ClinicalTrials.gov ID
- NCT01359722
- Acronym / sponsor ID
- 0992/09
- Conditions
- Kidney Failure, Acute, Oxidative Stress Induction
- Keywords
- N-acetylcysteine, Myocardial Revascularization, Acute Renal Failure, Oxidative Stress
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Instituto do CoracaoOther government
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Study start
- Mar 2010
- Primary completion
- Dec 2011 (estimated)
- Study completion
- Dec 2012 (estimated)
- First posted
- 25 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| N-Acetylcysteine | Experimental | Drug: N-acetylcysteineN-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 | Placebo comparator | Drug: ControlThis group will receive only the infusion of saline in the same doses and infusion rate. |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineAlso: FluimucilN-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. | Drug | N-Acetylcysteine |
| ControlAlso: salineThe control group will receive only the infusion of saline in the same doses and infusion rate. | Drug | Control |
Primary outcome
Decrease in glomerular filtration defined by at least 30% compared to preoperative levels .
Time frame: Within the first 72 hours postoperatively
7 secondary outcomes
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.
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.
Need for dialysis
Time frame: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
Cardiovascular morbidity.
Time frame: Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively.
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.
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.
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2011.
- Background: PubMed 9783643Suen 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.
- Background: PubMed 10900277Tepel 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.
- Background: PubMed 12392825Shyu 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.
- Background: PubMed 11470263Mazzon 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.
- Background: PubMed 12821233Baker 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jose Jayme G de Lima, phD principal investigator
Instito do Coracao-HCFMUSP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing N-acetylcysteine in people with Kidney Failure, Acute and Oxidative Stress Induction, run by Instituto do Coracao at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jose Jayme G de Lima, phD (+5511-30695048, eduesley.santos@incor.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Decrease in glomerular filtration defined by at least 30% compared to preoperative levels . (time frame: Within the first 72 hours postoperatively). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01359722, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2011.