N-Acetylcysteine to Prevent Radiocontrast Nephropathy in Emergency Department Patients

NCT ID: NCT00780962

Last Updated: 2024-10-29

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

399 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-10-16

Study Completion Date

2010-08-09

Brief Summary

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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

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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.

Conditions

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Radiocontrast Nephropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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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.

Group Type EXPERIMENTAL

N-Acetylcysteine (NAC)

Intervention Type DRUG

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.

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.

Group Type PLACEBO_COMPARATOR

0.9% Sodium-chloride

Intervention Type DRUG

Placebo:

* Before CT: 500 cc 0.9% Sodium-chloride
* After CT: NS at 67 cc/hour for up to 24 hours.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Acetadote Normal Saline

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cumberland Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Nathan Shapiro

Associate Professor of Emergency Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Stephen J Traub, MD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center, Boston

Locations

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Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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Baker CS, Wragg A, Kumar S, De Palma R, Baker LR, Knight CJ. A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study. J Am Coll Cardiol. 2003 Jun 18;41(12):2114-8. doi: 10.1016/s0735-1097(03)00487-x.

Reference Type BACKGROUND
PMID: 12821233 (View on PubMed)

Gupta R, Gurm HS, Bhatt DL, Chew DP, Ellis SG. Renal failure after percutaneous coronary intervention is associated with high mortality. Catheter Cardiovasc Interv. 2005 Apr;64(4):442-8. doi: 10.1002/ccd.20316.

Reference Type BACKGROUND
PMID: 15789398 (View on PubMed)

Hipp A, Desai S, Lopez C, Sinert R. The incidence of contrast-induced nephropathy in trauma patients. Eur J Emerg Med. 2008 Jun;15(3):134-9. doi: 10.1097/MEJ.0b013e328270367d.

Reference Type BACKGROUND
PMID: 18460952 (View on PubMed)

Kao LW, Kirk MA, Furbee RB, Mehta NH, Skinner JR, Brizendine EJ. What is the rate of adverse events after oral N-acetylcysteine administered by the intravenous route to patients with suspected acetaminophen poisoning? Ann Emerg Med. 2003 Dec;42(6):741-50. doi: 10.1016/s0196-0644(03)00508-0.

Reference Type BACKGROUND
PMID: 14634597 (View on PubMed)

Kay J, Chow WH, Chan TM, Lo SK, Kwok OH, Yip A, Fan K, Lee CH, Lam WF. Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial. JAMA. 2003 Feb 5;289(5):553-8. doi: 10.1001/jama.289.5.553.

Reference Type BACKGROUND
PMID: 12578487 (View on PubMed)

Marenzi G, Assanelli E, Marana I, Lauri G, Campodonico J, Grazi M, De Metrio M, Galli S, Fabbiocchi F, Montorsi P, Veglia F, Bartorelli AL. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med. 2006 Jun 29;354(26):2773-82. doi: 10.1056/NEJMoa054209.

Reference Type BACKGROUND
PMID: 16807414 (View on PubMed)

Marenzi G, Lauri G, Assanelli E, Campodonico J, De Metrio M, Marana I, Grazi M, Veglia F, Bartorelli AL. Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction. J Am Coll Cardiol. 2004 Nov 2;44(9):1780-5. doi: 10.1016/j.jacc.2004.07.043.

Reference Type BACKGROUND
PMID: 15519007 (View on PubMed)

Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, Bersin RM, Van Moore A, Simonton CA 3rd, Rittase RA, Norton HJ, Kennedy TP. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004 May 19;291(19):2328-34. doi: 10.1001/jama.291.19.2328.

Reference Type BACKGROUND
PMID: 15150204 (View on PubMed)

Rashid ST, Salman M, Myint F, Baker DM, Agarwal S, Sweny P, Hamilton G. Prevention of contrast-induced nephropathy in vascular patients undergoing angiography: a randomized controlled trial of intravenous N-acetylcysteine. J Vasc Surg. 2004 Dec;40(6):1136-41. doi: 10.1016/j.jvs.2004.09.026.

Reference Type BACKGROUND
PMID: 15622367 (View on PubMed)

Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, Singh M, Bell MR, Barsness GW, Mathew V, Garratt KN, Holmes DR Jr. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation. 2002 May 14;105(19):2259-64. doi: 10.1161/01.cir.0000016043.87291.33.

Reference Type BACKGROUND
PMID: 12010907 (View on PubMed)

Smilkstein MJ, Bronstein AC, Linden C, Augenstein WL, Kulig KW, Rumack BH. Acetaminophen overdose: a 48-hour intravenous N-acetylcysteine treatment protocol. Ann Emerg Med. 1991 Oct;20(10):1058-63. doi: 10.1016/s0196-0644(05)81352-6.

Reference Type BACKGROUND
PMID: 1928874 (View on PubMed)

Traub SJ, Mitchell AM, Jones AE, Tang A, O'Connor J, Nelson T, Kellum J, Shapiro NI. N-acetylcysteine plus intravenous fluids versus intravenous fluids alone to prevent contrast-induced nephropathy in emergency computed tomography. Ann Emerg Med. 2013 Nov;62(5):511-520.e25. doi: 10.1016/j.annemergmed.2013.04.012. Epub 2013 Jun 14.

Reference Type RESULT
PMID: 23769807 (View on PubMed)

Traub SJ, Kellum JA, Tang A, Cataldo L, Kancharla A, Shapiro NI. Risk factors for radiocontrast nephropathy after emergency department contrast-enhanced computerized tomography. Acad Emerg Med. 2013 Jan;20(1):40-5. doi: 10.1111/acem.12059.

Reference Type RESULT
PMID: 23570477 (View on PubMed)

Other Identifiers

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2007P000095

Identifier Type: -

Identifier Source: org_study_id

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