N-Acetylcysteine to Prevent Radiocontrast Nephropathy in Emergency Department Patients

Radiocontrast Nephropathy Clinical Trial

Official title:

N-Acetylcysteine to Prevent Radiocontrast Nephropathy in Emergency Department Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00780962
• Other study ID #: 2007P000095
• Status: Completed
• Phase: Phase 2
• Start date: October 16, 2007
• Est. completion date: August 9, 2010

Study information

• Verified date: November 2018
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 399
• Est. completion date: August 9, 2010
• Est. primary completion date: August 9, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Emergencies
• Kidney Diseases
• Radiocontrast Nephropathy

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center	Cumberland Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (13)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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 — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Contrast-induced Nephropathy	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