N-Acetylcysteine to Prevent Radiocontrast Nephropathy in Emergency Department Patients

Phase 2

Completed

Conditions: Radiocontrast Nephropathy

Interventions: Drug: 0.9% Sodium-chloride
Drug: N-Acetylcysteine (NAC)

Registration Number: NCT00780962

Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary: Multiple agents have been studied to prevent radiocontrast nephropathy. One of these agents is N-Acetylcysteine. Previous trials to assess N-Acetylcysteine's efficacy in the prevention of contrast nephropathy have been promising. However, previous studies have limited applicability to the Emergency Department (ED) patient population for two reasons:

* 1) Many of the pretreatment strategies employed in these studies take several hours or even days to perform, which is not feasible in acutely ill ED patients.

* 2) Most of these studies were conducted in patients undergoing cardiac catheterization. This may be a very different population than patients in the ED undergoing abdominal or chest computed tomography.

The investigators wish to study the efficacy of N-acetylcysteine as an agent to prevent radiocontrast nephropathy in ED patients undergoing computerized tomography. The investigators propose a randomized, double-blind, controlled trial comparing saline hydration plus N-acetylcysteine versus saline hydration alone. The hypothesis of this study is that N-acetylcysteine with normal saline will be more effective than saline alone in the prevention of radiocontrast nephropathy.

Detailed Description: Out of the approximately 110 million Emergency Department (ED) visits in the United States each year approximately 8.8 million people undergo Contrast-Enhanced Computerized Tomography (CT) studies in United States EDs each year (based on the investigators experience).

Radiocontrast nephropathy is a serious potential consequence associated with significant morbidity and mortality. Preliminary data suggests that the rate of Radiocontrast Induced Nephropathy after Emergency Department CT is approximately 5-7%. This figure, coupled with our estimate of 8.8 million contrast-enhanced CT studies, suggests that there are somewhere between 440,000 and 616,000 cases of radiocontrast nephropathy in the US each year that are caused by ED studies.

Multiple agents have been studied to prevent radiocontrast nephropathy. One of these agents is N-Acetylcysteine. There is inconclusive evidence about the benefit of this intervention. Some studies have shown that N-Acetylcysteine administered in either a high-dose intravenous protocol or a low-dose intravenous plus oral protocol may reduce the incidence of radiocontrast nephropathy in patients undergoing emergent cardiac catheterization, although other studies have found no benefit.

It is not clear, however, if these studies generalize to the ED patient undergoing emergency CT. ED patients often have different comorbidities or higher acuity which may limit the applicability in the ED patient population for two reasons:

* 1) Many of the pretreatment strategies employed in these studies take several hours or even days to perform, which is not feasible in acutely ill ED patients.

* 2) Most of these studies were conducted in patients undergoing cardiac catheterization. This may be a very different population than patients in the ED undergoing abdominal or chest computed tomography.

The investigators wish to study the efficacy of N-acetylcysteine as an agent to prevent radiocontrast nephropathy in ED patients undergoing computerized tomography. The investigators propose a randomized, double-blind, controlled trial comparing saline hydration plus N-acetylcysteine versus saline hydration alone. The hypothesis of this study is that N-acetylcysteine with normal saline will be more effective than saline alone in the prevention of radiocontrast nephropathy.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 399

Inclusion Criteria

Undergoing a CT with intravenous contrast as part of clinical care
18 years of age or older
Willingness to have a serum creatinine measured 48-72 hours after study
Presence of one or more risk factors for radiocontrast nephropathy:
- Creatinine greater than or equal to 1.4 mg/dL
- Estimated Glomerular Filtration Rate (eGFR) of less than 60 mL/min/1.73m2
- Diabetes Mellitus
- Hypertension being treated with anti-hypertensive mediations
- Coronary artery disease
- Concurrent use of any of the following nephrotoxic drugs:
  - Cyclosporine A
  - Aminoglycosides
  - Amphotericin
  - Cisplatin
  - Non-steroidal anti-inflammatory drugs
  - Congestive heart failure (active or by history)
  - Older age (65 years of age or older)
  - Anemia (hematocrit < 30%)

Exclusion Criteria

Unable or unwilling to provide informed consent
End-stage renal disease currently undergoing regular hemodialysis
Pregnant
Known allergy to N-acetylcysteine
Too unstable to wait for infusion of medication or placebo
Treating physician using N-Acetylcysteine as part of clinical care

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
0.9% Sodium-chloride group	0.9% Sodium-chloride	Subjects in this group will receive 500 cc Normal Saline (0.9% Sodium Chloride) over 30 minutes prior to contrast administration. After contrast administration, they will receive a continuous infusion of 67 cc per hour of normal saline. The infusion will be administered for a minimum of two hours and then stopped after 24 hours, or when the patient is discharged from the Emergency Department or the hospital, whichever comes first.
N-Acetylcysteine group	N-Acetylcysteine (NAC)	Subjects in this group will receive 3 grams of N-acetylcysteine in 500 cc normal saline (0.9% Sodium Chloride) over 30 minutes prior to contrast administration. After contrast administration, they will receive a continuous infusion of 200 mg N-acetylcysteine per hour. This dose will be administered as an infusion of 67 cc per hour of a solution of 3 grams of N-acetylcysteine in 1000 cc of normal saline. The infusion will be administered for a minimum of two hours and then stopped after 24 hours, or when the patient is discharged from the Emergency Department or the hospital, whichever comes first.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Contrast-induced Nephropathy	48-72 hours	Contrast-induced nephropathy was defined as an increase in serum creatinine level of greater than or equal to 0.5 mg/dL or an increase of 25% above baseline. The primary outcome was measured by the change in serum creatinine level from the pre-radiocontrast baseline to the serum creatinine level measured 48 to 72 hours after radiocontrast administration.

Secondary Outcome Measures