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

Phase 2

Completed

• Conditions: Kidney Failure, Acute; Kidney Failure, Chronic; Cardiac Surgical Procedures
• Interventions: Drug: fenoldopam; Drug: N-acetylcysteine

• Registration Number: NCT00122018
• Lead Sponsor: Linda F. Barr, M.D.

Brief Summary

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

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).

Study Timeline

• Study Start: 2002-05
• Study First Submitted: 2005-07-14
• Study First Submitted QC: 2005-07-20
• Study First Posted: 2005-07-21
• Primary Completion: 2006-03
• Study Completion: 2006-03
• Status Verified: 2014-11
• Last Update Submitted: 2014-11-06
• Last Update Posted: 2014-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
fenoldopam	fenoldopam	fenoldopam started at surgery continued for 24 hours
NAC and fenoldopam	fenoldopam	Both N-acetylcysteine and fenoldopam as above
NAC	N-acetylcysteine	N-acetylcysteine started day prior to surgery, continued through night of surgery
NAC and fenoldopam	N-acetylcysteine	Both N-acetylcysteine and fenoldopam as above

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Intraoperative and post-operative pressor use (pressor-hours)	48 hour
Hospital costs	30-day
Mortality	30-day
Days to post-operative creatinine clearance nadir	14 day