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

This study has been completed.
Sponsor:
Collaborators:
Martin, Claudio M., M.D.
Fran Priestap
Information provided by:
St. Michael's Hospital, Toronto
ClinicalTrials.gov Identifier:
NCT00830193
First received: January 13, 2009
Last updated: January 26, 2009
Last verified: January 2009
  Purpose

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.


Condition Intervention Phase
Contrast Induced Nephropathy
Critically Ill
Drug: N-acetylcysteine
Drug: D5W Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: N-Acetylcysteine in Critically Ill Patients Undergoing Contrast Enhanced Computed Tomography: A Randomized Trial

Resource links provided by NLM:


Further study details as provided by St. Michael's Hospital, Toronto:

Primary Outcome Measures:
  • 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. [ Time Frame: 5 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ICU length of stay [ Time Frame: ICU stay ] [ Designated as safety issue: No ]
  • Hospital length of stay [ Time Frame: Hospital stay ] [ Designated as safety issue: No ]
  • ICU mortality [ Time Frame: ICU stay ] [ Designated as safety issue: No ]
  • Hospital Mortality [ Time Frame: Hospital stay ] [ Designated as safety issue: No ]
  • Requirement for Renal Replacement Therapy [ Time Frame: ICU ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: August 2002
Study Completion Date: May 2005
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: D5W

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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00830193

Locations
Canada, Ontario
London Health Sciences Centre - Victoria Hospital
London, Ontario, Canada, N6A 4G5
London Health Sciences Centre - University Hospital Campus
London, Ontario, Canada, N6A 5A5
Sponsors and Collaborators
St. Michael's Hospital, Toronto
Martin, Claudio M., M.D.
Fran Priestap
Investigators
Study Director: Claudio M Martin, MD, FRCPC, MSc London Health Sciences Centre - Victoria Hospital
  More Information

No publications provided

Responsible Party: Dr. Claudio Martin, London Health Sciences Centre - Victoria Hospital
ClinicalTrials.gov Identifier: NCT00830193     History of Changes
Other Study ID Numbers: LHRI-000001
Study First Received: January 13, 2009
Last Updated: January 26, 2009
Health Authority: Canada: Health Canada

Keywords provided by St. Michael's Hospital, Toronto:
N-acetylcysteine
prevention
contrast-induced nephropathy
critically ill adults

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

ClinicalTrials.gov processed this record on September 18, 2014