N-Acetylcysteine to Prevent Radiocontrast Nephropathy in Emergency Department Patients

Beth Israel Lahey Health

Status and phase: Completed; Phase 2

Conditions: Radiocontrast Nephropathy

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00780962

2007P000095

Details and patient eligibility

About

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.

Full 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.

Enrollment: 399 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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399 participants in 2 patient groups, including a placebo group

N-Acetylcysteine group

Experimental group

Description:

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.

Treatment:

Drug: N-Acetylcysteine (NAC)

0.9% Sodium-chloride group

Placebo Comparator group

Description:

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.

Treatment:

Drug: 0.9% Sodium-chloride