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

Critically Ill Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00830193
• Other study ID #: LHRI-000001
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 13, 2009
• Last updated: January 26, 2009
• Start date: August 2002
• Est. completion date: May 2005

Study information

• Verified date: January 2009
• Source: St. Michael's Hospital, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: May 2005
• Est. primary completion date: May 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Contrast Induced Nephropathy
• Critical Illness
• Critically Ill
• Kidney Diseases

Intervention

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).
• 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).

Locations

Country	Name	City	State
Canada	London Health Sciences Centre - University Hospital Campus	London	Ontario
Canada	London Health Sciences Centre - Victoria Hospital	London	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
St. Michael's Hospital, Toronto	Fran Priestap, Martin, Claudio M., M.D.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	ICU length of stay		ICU stay	No
Secondary	Hospital length of stay		Hospital stay	No
Secondary	ICU mortality		ICU stay	No
Secondary	Hospital Mortality		Hospital stay	No
Secondary	Requirement for Renal Replacement Therapy		ICU	No