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

Linda F. Barr, M.D.

Status and phase: Completed; Phase 2

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

Treatments: Drug: N-acetylcysteine; Drug: fenoldopam

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00122018

REPORT

Details and patient eligibility

About

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.

Full description

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).

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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80 participants in 4 patient groups, including a placebo group

NAC

Experimental group

Description:

N-acetylcysteine started day prior to surgery, continued through night of surgery

Treatment:

Drug: N-acetylcysteine

fenoldopam

Experimental group

Description:

fenoldopam started at surgery continued for 24 hours

Treatment:

Drug: fenoldopam

NAC and fenoldopam

Experimental group

Description:

Both N-acetylcysteine and fenoldopam as above

Treatment:

Drug: fenoldopam

Drug: N-acetylcysteine

Control

Placebo Comparator group

Description:

Placebo