Clinical trial NCT00780962: N-Acetylcysteine to Prevent Radiocontrast Nephropathy in Emergency Department Patients
Official title: N-Acetylcysteine to Prevent Radiocontrast Nephropathy in Emergency Department Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Radiocontrast Nephropathy
Keywords: NAC
Radiocontrast Nephropathy
N-Acetylcysteine
RCN
RCIN
Creatinine
Computerized Tomography
CT
Emergency Department
ED
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Cumberland Pharmaceuticals
First posted: 2008-10-28
Enrollment: 399
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized to receive either of two interventions: N-acetylcysteine (Treatment group) or Normal Saline (Placebo group).

Patients in the treatment group will receive 3 g of Nacetylcysteine in 500mL normal saline (0.9% Sodium Chloride) solution during 30 minutes before contrast administration. After contrast administration, patients will receive a continuous infusion of 200mg of N-acetylcysteine per hour, administered as an infusion of 67 mL per hour of a solution of 3 g of N-acetylcysteine diluted to a total volume of 1,000 mL with normal saline solution.

Patients in the placebo group will receive 500 mL of normal saline solution during 30 minutes before contrast administration and a continuous infusion of 67 mL per hour of normal saline solution after contrast administration.

Patients in both arms will receive the postcontrast infusion (N-acetylcysteine or saline solution) for a minimum of 2 hours.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Contrast-induced Nephropathy
timeFrame: 48-72 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center, Boston
name: Stephen J Traub, MD
role: PRINCIPAL_INVESTIGATOR
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