Mechanisms for the Effect of Acetylcysteine on Renal Function After Exposure to Radiographic Contrast Material

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2010 by University of Edinburgh.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
NHS Lothian
Information provided by:
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT00558142
First received: November 13, 2007
Last updated: June 24, 2010
Last verified: June 2010
  Purpose

Millions of people receive radiographic contrast material for investigations like CT and coronary angiography. While considered safe in healthy patients, it can cause acute renal impairment. This is termed radiocontrast-induced nephropathy (RCIN) and is generally defined as an increase in serum creatinine over baseline of more than 25% or 0.5 mg/dL (44.2 μmol/l) within 48 hrs. RCIN occurs in less than 2% of patients with normal renal function but is more common in patients with pre-existing renal damage.

The pathophysiology of RCIN is unclear. Possible mechanisms involve 1) reduced renal blood flow leading to acute tubular necrosis and 2) direct renal tubular injury by oxygen free radicals. Current prevention strategies focus on increasing renal blood flow and reducing oxidative stress. Patients at risk of RCIN currently receive fluids, a low dose of contrast, and variable and unproven doses of acetylcysteine.

The evidence for acetylcysteine administration is unclear. A RCIN consensus working group reported in the American Journal of Cardiology in September 2006 that "N-acetylcysteine is not consistently effective in reducing the risk for contrast-induced nephropathy". The perception of a benefit from acetylcysteine administration that is unproven has disadvantages as some clinicians report giving larger amounts of radio-contrast to patients who have received acetylcysteine since they believe that it prevents RCIN. There is a need to determine how acetylcysteine might prevent RCIN and to identify the appropriate dose and route of administration.

Since acetylcysteine is a vasodilator as well as an antioxidant, it may work in two distinct ways, by preventing reduction in renal blood flow (RBF) or contrast-induced oxidative damage. Previous studies have used changes in serum creatinine. In addition to being an insensitive marker of altered renal function, if contrast causes renal vasoconstriction and acetylcysteine vasodilatation, changes in serum creatinine will not be the ideal marker of effect. Finally the optimum dose and route of acetylcysteine administration is unclear, as illustrated by studies using a variety of doses and routes.

We propose to study the mechanism of effects of acetylcysteine on healthy and diseased kidneys, both unstressed and stressed by radiocontrast administration. We hypothesise that acetylcysteine may exert a renoprotective effect in RCIN by a renal vasodilatation and/or antioxidant mechanism.


Condition Intervention Phase
Radiocontrast-Induced Nephropathy
Drug: Acetylcysteine
Drug: Visipaque 320
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Mechanisms for the Effect of Acetylcysteine on Renal Function After Exposure to Radiographic Contrast Material

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • Changes in renal blood flow [ Time Frame: 7 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in glomerular filtration rate, tubular function, oxidative balance. [ Time Frame: 7 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: February 2008
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Healthy volunteers will be randomised to receive either placebo capsules PO plus an infusion of normal saline, acetylcysteine capsules PO plus an infusion of normal saline or placebo capsules PO plus an IV infusion of acetylcysteine in normal saline
Drug: Acetylcysteine
Participants will receive packs of either 8 placebo capsules or 8 acetylcysteine (600mg) capsules. They will be asked to take 2 tablets at 08.00 and 22.00 on the day before the study and the day of the study. On the day of the study participants will receive an IV infusion of either normal saline or acetylcysteine (200mg/kg)
Other Name: Parvolex
Active Comparator: 2
Volunteers with CKD III will be randomised to receive either placebo capsules PO plus an infusion of normal saline, acetylcysteine capsules PO plus an infusion of normal saline or placebo capsules PO plus an IV infusion of acetylcysteine in normal saline
Drug: Acetylcysteine
Participants will receive packs of either 8 placebo capsules or 8 acetylcysteine (600mg) capsules. They will be asked to take 2 tablets at 08.00 and 22.00 on the day before the study and the day of the study. On the day of the study participants will receive an IV infusion of either normal saline or acetylcysteine (200mg/kg)
Other Name: Parvolex
Active Comparator: 3
Healthy volunteers will receive a single IV dose of 100mls Visipaque 320 (iodixanol, equivalent to 320 mg iodine/ml). They will then be randomised to receive either placebo capsules PO plus an infusion of normal saline, acetylcysteine capsules PO plus an infusion of normal saline or placebo capsules PO plus an IV infusion of acetylcysteine in normal saline
Drug: Acetylcysteine
Participants will receive packs of either 8 placebo capsules or 8 acetylcysteine (600mg) capsules. They will be asked to take 2 tablets at 08.00 and 22.00 on the day before the study and the day of the study. On the day of the study participants will receive an IV infusion of either normal saline or acetylcysteine (200mg/kg)
Other Name: Parvolex
Drug: Visipaque 320
100mls IV dose as single dose
Other Name: Iodixanol
Active Comparator: 4
Volunteers with CKD III will receive Visipaque 320 during coronary angiography. They will have been randomised to receive either placebo capsules PO plus an infusion of normal saline, acetylcysteine capsules PO plus an infusion of normal saline or placebo capsules PO plus an IV infusion of acetylcysteine in normal saline
Drug: Acetylcysteine
Participants will receive packs of either 8 placebo capsules or 8 acetylcysteine (600mg) capsules. They will be asked to take 2 tablets at 08.00 and 22.00 on the day before the study and the day of the study. On the day of the study participants will receive an IV infusion of either normal saline or acetylcysteine (200mg/kg)
Other Name: Parvolex
Drug: Visipaque 320
The dose of Visipaque will be administered by the consultant cardiologist performing the coronary angiography
Other Name: Iodixanol

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Study 1 and 3: Healthy male volunteers over 45 years of age with BMI between 22 and 40.
  • Study 2: Male volunteers with CKD III with BMI between 22 and 40.
  • Study 4: Male patients over 45 year of age with stable CKD III and BMI between 22 and 40, undergoing elective coronary angiography.

Exclusion Criteria for studies 1 and 3:

  • Lack of informed consent
  • Age <46 years
  • Current involvement in a clinical trial
  • Clinically significant co-morbidity: heart failure, hypertension, known hyperlipidaemia, diabetes mellitus, coagulopathy, peripheral vascular disease, or bleeding disorder
  • thyroid disease, myasthenia gravis, asthma, atopy, or a history of allergy/sensitivity to acetylcysteine or contrast medium
  • current intake of prescription medicines, in particular beta blockers
  • recent infective/inflammatory condition
  • blood donation during the preceding three months

Exclusion criteria for studies 2 and 4:

  • Lack of informed consent
  • Age <46 years
  • Current involvement in a clinical trial
  • Thyroid disease, myasthenia gravis, asthma, atopy, or a history of allergy/sensitivity to acetylcysteine or contrast medium
  • Recent infective/inflammatory condition
  • Blood donation during the preceding three months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00558142

Contacts
Contact: Michael Eddleston, MA PhD MRCP +44 131 242 1360 eddlestonm@yahoo.com
Contact: Euan Sandilands, BSc MRCP +44 131 242 1360 euan.sandilands@luht.scot.nhs.uk

Locations
United Kingdom
Clinical Research Facility, Royal Infirmary Edinburgh Recruiting
Edinburgh, Midlothian, United Kingdom, EH16 4SA
Contact: Joanne M Mair    +44 131 537 2591      
Principal Investigator: Michael Eddleston, MA PhD MRCP         
Sub-Investigator: Euan Sandilands, BSc MRCP         
Sponsors and Collaborators
University of Edinburgh
NHS Lothian
Investigators
Principal Investigator: Michael Eddleston, MA PhD MCRP University of Edinburgh
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Michael Eddleston, University of Edinburgh
ClinicalTrials.gov Identifier: NCT00558142     History of Changes
Other Study ID Numbers: NAC0606, NRES reference: 07/MRE00/64, EudraCT reference: 2006, 003509-18
Study First Received: November 13, 2007
Last Updated: June 24, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Edinburgh:
contrast nephropathy
radiocontrast-induced nephropathy
chronic kidney disease
acetylcysteine
clinical study

Additional relevant MeSH terms:
Kidney Diseases
Urologic Diseases
Acetylcysteine
N-monoacetylcystine
Iodixanol
Contrast Media
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
Diagnostic Uses of Chemicals

ClinicalTrials.gov processed this record on September 18, 2014