N-Acetylcysteine to Prevent Radiocontrast Nephropathy in Emergency Department Patients

November 7, 2018 updated by: Nathan Shapiro, Beth Israel Deaconess Medical Center

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

399

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: N-Acetylcysteine group
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.
Drug: N-Acetylcysteine (NAC)

Experimental:

  • Before CT: 3 g NAC IV in 500 cc of 0.9% Sodium-chloride
  • After CT: 200 mg NAC/hour in 0.9% Sodium-chloride at 67 cc/hour for up to 24 hours.
Other Names:
  • Acetadote
PLACEBO_COMPARATOR: 0.9% Sodium-chloride group
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.
Drug: 0.9% Sodium-chloride

Placebo:

  • Before CT: 500 cc 0.9% Sodium-chloride
  • After CT: NS at 67 cc/hour for up to 24 hours.
Other Names:
  • Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Contrast-induced Nephropathy
Time Frame: 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.
48-72 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beth Israel Deaconess Medical Center

Collaborators

Cumberland Pharmaceuticals

Investigators

  • Principal Investigator: Stephen J Traub, MD, Beth Israel Deaconess Medical Center, Boston

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 16, 2007

Primary Completion (ACTUAL)

August 9, 2010

Study Completion (ACTUAL)

August 9, 2010

Study Registration Dates

First Submitted

October 27, 2008

First Submitted That Met QC Criteria

October 27, 2008

First Posted (ESTIMATE)

October 28, 2008

Study Record Updates

Last Update Posted (ACTUAL)

November 9, 2018

Last Update Submitted That Met QC Criteria

November 7, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2007P000095

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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