An Investigation of N-acetylcysteine and Fenoldopam as Renal Protection Agents for Cardiac Surgery

Study Overview
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Brief Summary
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Patients with abnormal kidney function are at increased risk for complications following heart surgery, including worsening kidney function possibly requiring dialysis, a prolonged stay in the critical care unit and hospital, and the increased risk of death. Prior attempts at kidney protection for heart surgery patients have had mixed results. Two medicines, fenoldopam and N-acetylcysteine, have been shown to protect kidney function in other circumstances that cause kidney stress. The purpose of this study is to determine whether these medications will help to maintain the function of diseased kidneys during heart surgery.

Detailed Description
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This is a randomized, double-blinded, placebo-controlled trial to evaluate fenoldopam and N-acetylcysteine (NAC) individually, and together, as renal protective agents for patients with renal insufficiency undergoing heart surgery. Subjects have chronic renal insufficiency with creatinine clearance (CrCl) </= 40cc/min but not on pre-operative dialysis, and receive: NAC 600 mg by mouth (po) twice a day (bid) or placebo starting 24 hours pre-operative and continuing through the day of surgery; and/or fenoldopam 0.1 mcg/kg/min intravenous (IV) or saline placebo at anesthetic induction and continuing for 48 hours. Outcome data include: nadir, post-operative day 3 and post-operative day 14 CrCl, time to CrCl nadir, length of Intensive Care Unit (ICU) stay, length of post-operative hospital stay, hospital costs, mortality, and the need for hemodialysis. Intraoperative and post-operative pressor use is being monitored. The enrollment will include 80 patients (20 in each group).

Official Title
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N-acetylcysteine and Fenoldopam Protect the Renal Function of Patients With Chronic Renal Insufficiency Undergoing Cardiac Surgery.

Conditions
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Kidney Failure, Acute, Kidney Failure, Chronic, Cardiac Surgical Procedures

Intervention / Treatment
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* Drug: N-acetylcysteine
* Drug: fenoldopam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic creatinine clearance </= 40cc/h Pre-operative cardiac surgery Exclusion Criteria: Pre-operative ongoing dialysis Nausea and vomiting Uncontrolled glaucoma Allergy to metabisulfite Enrollment in another clinical study within 30 days Pregnancy Acute renal failure

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NAC<br>N-acetylcysteine started day prior to surgery, continued through night of surgery | Drug: N-acetylcysteine<br> <br> * Other names: Mucomyst;|
| Experimental: fenoldopam<br>fenoldopam started at surgery continued for 24 hours | Drug: fenoldopam<br> <br> * Other names: Corlopam;|
| Experimental: NAC and fenoldopam<br>Both N-acetylcysteine and fenoldopam as above | Drug: N-acetylcysteine<br> <br> * Other names: Mucomyst;Drug: fenoldopam<br> <br> * Other names: Corlopam;|
| Placebo Comparator: Control<br>Placebo | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of post-operative hospital stay |  | 30-day | 
| Length of post-operative critical care stay |  | 30-day | 
| Creatinine clearance post-operative days 3, 14, and nadir |  | 14 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days to post-operative creatinine clearance nadir |  | 14 day | 
| Intraoperative and post-operative pressor use (pressor-hours) |  | 48 hour | 
| Hospital costs |  | 30-day | 
| Mortality |  | 30-day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney failure, Cardiac Surgery, Fenoldopam, N-acetylcysteine