N-Acetylcysteine to Prevent Radiocontrast Nephropathy in Emergency Department Patients

NCT00780962 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2007P000095
• Study Type: interventional
• Target: 399
• Locations: 1 country
• Sites: 1

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.

Conditions

Radiocontrast Nephropathy

Keywords

NAC; Radiocontrast Nephropathy; N-Acetylcysteine; RCN; RCIN; Creatinine; Computerized Tomography; CT; Emergency Department; ED

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

N-Acetylcysteine group

EXPERIMENTAL

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)

0.9% Sodium-chloride group

PLACEBO COMPARATOR

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

Interventions

N-Acetylcysteine (NAC) 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.

Also known as: Acetadote

N-Acetylcysteine group

0.9% Sodium-chloride DRUG

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

Also known as: Normal Saline

0.9% Sodium-chloride group

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Undergoing a CT with intravenous contrast as part of clinical care
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Cumberland Pharmaceuticals: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related 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. doi: 10.1016/s0735-1097(03)00487-x.

  PMID: 12821233 BACKGROUND

• 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.

  PMID: 15789398 BACKGROUND

• 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.

  PMID: 18460952 BACKGROUND

• 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.

  PMID: 14634597 BACKGROUND

• 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.

  PMID: 12578487 BACKGROUND

• 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.

  PMID: 16807414 BACKGROUND

• 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.

  PMID: 15519007 BACKGROUND

• 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.

  PMID: 15150204 BACKGROUND

• 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.

  PMID: 15622367 BACKGROUND

• 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.

  PMID: 12010907 BACKGROUND

• 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.

  PMID: 1928874 BACKGROUND

• 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.

  PMID: 23769807 RESULT

• 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.

  PMID: 23570477 RESULT

MeSH Terms

Conditions

Emergencies

Interventions

Acetylcysteine; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Our results were obtained in patients considered to be at relatively low risk for contrast-induced nephropathy and should not be extended to patients who might be at higher risk for it.

Results Point of Contact

• Title: Nathan I. Shapiro, MD, MPH
• Organization: Beth Israel Deaconess Medical Center

nshapiro@bidmc.harvard.edu

617-754-2323

Study Officials

• Stephen J Traub, MD

  Beth Israel Deaconess Medical Center, Boston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Emergency Medicine

Model Details: 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.

Study Record Dates

• First Submitted: October 27, 2008
• First Posted: October 28, 2008
• Study Start: October 16, 2007
• Primary Completion: August 9, 2010
• Study Completion: August 9, 2010
• Last Updated: October 29, 2024
• Results First Posted: January 31, 2018

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)