N-Acetylcysteine in Critically Ill Patients Undergoing Contrast Enhanced Computed Tomography

N-Acetylcysteine in Critically Ill Patients Undergoing Contrast Enhanced Computed Tomography: A Randomized Trial

Critically ill patients frequently undergo contrast enhanced computed tomography (CT) to establish diagnoses and direct management. Contrast agents can disturb kidney function and result in kidney dysfunction. The investigators investigated the effects of high dose N-acetylcysteine (NAC) or placebo, in addition to hydration, in preventing kidney dysfunction following contrast enhanced CT) in critically ill adults in the intensive care units of two teaching hospitals.

Study Overview

• Status: Completed
• Conditions: Critically Ill; Contrast Induced Nephropathy
• Intervention / Treatment: Drug: N-acetylcysteine; Drug: D5W Placebo

Detailed Description

Potential participants were identified by staff intensivists or resident physicians following admission to participating ICUs. We included critically ill adult patients at least 18 years of age who consented to participate in the trial, had central venous access and a foley catheter, required a contrast-enhanced CT of any organ system(s), and were considered 'at risk' for the development of CIN. We defined 'at risk' to include patients with at least one of the following at the time of randomization (i) a serum creatinine of > 106 µmol/L and or urea > 6 mmol/L, (ii) urine output of < 0.5 cc/kg over > 4 hrs or (iii) an increase in serum creatinine of > 50 µmol/L in < 24 hours. We stratified based on the presence or absence of diabetes defined as a history of treatment with oral hypoglycemics or insulin.

We excluded patients with a (i) CK > 5,000 or the presence of myoglobinuria, (ii) a known allergy or hypersensitivity reaction to radiographic contrast dye or NAC, (iii) serious illness with imminent threat of dying (low likelihood of survival within 48-hours) or poor prognosis, (iv) pregnancy, (v) patients with cardiogenic shock (NYHA class 3 or 4 symptoms), (vi) known or suspected nephritic, nephrotic or pulmonary-renal syndromes, (vii) a post renal etiology of renal impairment, (viii) previous renal transplant, (ix) known solitary kidney, (x) serum creatinine > 200 µmol/L or (xi) recent exposure to radiographic contrast within 14 days of randomization.

The primary outcome for the study was the development of CIN defined as a rise in serum creatinine of > 50 µmol/L from the time of randomization up to day 5 following contrast exposure.

Secondary outcomes included ICU and hospital length of stay, ICU and hospital mortality and the requirement for renal replacement therapy. We recorded compliance with assigned treatment and assessed for development of severe unexpected adverse events defined as hypotension, bronchospasm and anaphylactic reactions.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4G5
      • London Health Sciences Centre - Victoria Hospital
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre - University Hospital Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The investigators included critically ill adult patients at least 18 years of age who consented to participate in the trial, had central venous access and a foley catheter, required a contrast-enhanced CT of any organ system(s), and were considered 'at risk' for the development of CIN.
• The investigators defined 'at risk' to include patients with at least one of the following at the time of randomization (i) a serum creatinine of > 106 µmol/L and or urea > 6 mmol/L, (ii) urine output of < 0.5 cc/kg over > 4 hrs or (iii) an increase in serum creatinine of > 50 µmol/L in < 24 hours.

Exclusion Criteria:

• The investigators excluded patients with a

  • CK > 5,000 or the presence of myoglobinuria
  • a known allergy or hypersensitivity reaction to radiographic contrast dye or NAC
  • serious illness with imminent threat of dying (low likelihood of survival within 48-hours) or poor prognosis
  • pregnancy
  • patients with cardiogenic shock (NYHA class 3 or 4 symptoms)
  • known or suspected nephritic, nephrotic or pulmonary-renal syndromes
  • a post renal etiology of renal impairment
  • previous renal transplant
  • known solitary kidney
  • serum creatinine > 200 µmol/L or (xi) recent exposure to radiographic contrast within 14 days of randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: N-acetylcysteine; Intravenous fluid administration was administered as soon as possible following randomization (not to exceed 12 hours prior to anticipated contrast exposure) and continued for 12 hours post CT. Patients randomized to the experimental arm received intravenous normal saline plus NAC 10 grams IV (5 g pre and 2.5 g at 6 and 12 hours post-exposure) for a total of 3 doses.	Drug: N-acetylcysteine; Medication packages were prepared and dispensed by pharmacy and included three premixed and prepackaged minibags containing either 5 g of NAC or placebo in 100 cc D5W (pre-CT dose) or 2.5 g of NAC or placebo in 50 cc D5W (post-CT doses).; Other Names: Mucomyst
Placebo Comparator: Placebo; Intravenous fluid administration was administered as soon as possible following randomization (not to exceed 12 hours prior to anticipated contrast exposure) and continued for 12 hours post CT. Medication packages were prepared and dispensed by pharmacy and included three premixed and prepackaged minibags containing either 5 g in 100 cc D5W (pre-CT dose) or 2.5 g in 50 cc D5W (post-CT doses). The placebo was D5W and was colour and consistency matched by pharmacy. Patients randomized to placebo received intravenous normal saline plus 3 doses of placebo.	Drug: D5W Placebo; Medication packages were prepared and dispensed by pharmacy and included three premixed and prepackaged minibags containing either 5 g of NAC or placebo (D5W) in 100 cc D5W (pre-CT dose) or 2.5 g NAC or placebo in 50 cc D5W (post-CT doses).; Other Names: D5W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome for the study was the development of CIN defined as a rise in serum creatinine of > 50 µmol/L from the time of randomization up to day 5 following contrast exposure.	5 days

Secondary Outcome Measures

Outcome Measure	Time Frame
ICU length of stay	ICU stay
Hospital length of stay	Hospital stay
ICU mortality	ICU stay
Hospital Mortality	Hospital stay
Requirement for Renal Replacement Therapy	ICU

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: Martin, Claudio M., M.D.; Fran Priestap
• Investigators: Study Director: Claudio M Martin, MD, FRCPC, MSc, London Health Sciences Centre - Victoria Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2002
• Primary Completion (Actual): May 1, 2005
• Study Completion (Actual): May 1, 2005

Study Registration Dates

• First Submitted: January 13, 2009
• First Submitted That Met QC Criteria: January 26, 2009
• First Posted (Estimate): January 27, 2009

Study Record Updates

• Last Update Posted (Estimate): January 27, 2009
• Last Update Submitted That Met QC Criteria: January 26, 2009
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Keywords: prevention; N-acetylcysteine; contrast-induced nephropathy; critically ill adults
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Kidney Diseases; Critical Illness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: LHRI-000001