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N-Acetylcysteine to Prevent Radiocontrast Nephropathy in Emergency Department Patients

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ClinicalTrials.gov Identifier: NCT00780962
Recruitment Status : Completed
First Posted : October 28, 2008
Results First Posted : January 31, 2018
Last Update Posted : January 31, 2018
Sponsor:
Collaborator:
Cumberland Pharmaceuticals
Information provided by (Responsible Party):
Nathan Shapiro, 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.


Condition or disease Intervention/treatment Phase
Radiocontrast Nephropathy Drug: N-Acetylcysteine (NAC) Drug: 0.9% Sodium-chloride Phase 2

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  (Clinical Trial)
Actual Enrollment : 399 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The study medication (or placebo) will come premixed from the pharmacy. There will be no external marks on the medication (or placebo) that suggests its identity.
Primary Purpose: Prevention
Official Title: N-Acetylcysteine to Prevent Radiocontrast Nephropathy in Emergency Department Patients
Actual Study Start Date : October 16, 2007
Actual Primary Completion Date : August 9, 2010
Actual Study Completion Date : August 9, 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

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 Name: 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 Name: Normal Saline




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00780962


Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Cumberland Pharmaceuticals
Investigators
Principal Investigator: Stephen J Traub, MD Beth Israel Deaconess Medical Center, Boston

Publications of Results:
Other Publications:

Responsible Party: Nathan Shapiro, Associate Professor of Emergency Medicine, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT00780962     History of Changes
Other Study ID Numbers: 2007P000095
First Posted: October 28, 2008    Key Record Dates
Results First Posted: January 31, 2018
Last Update Posted: January 31, 2018
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nathan Shapiro, Beth Israel Deaconess Medical Center:
NAC
Radiocontrast Nephropathy
N-Acetylcysteine
RCN
RCIN
Creatinine
Computerized Tomography
CT
Emergency Department
ED

Additional relevant MeSH terms:
Emergencies
Kidney Diseases
Disease Attributes
Pathologic Processes
Urologic Diseases
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes