Prevention of Serious Adverse Events Following Angiography (PRESERVE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Department of Veterans Affairs
Sponsor:
Collaborator:
The George Institute
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01467466
First received: October 26, 2011
Last updated: September 19, 2014
Last verified: September 2014

October 26, 2011
September 19, 2014
February 2013
March 2016   (final data collection date for primary outcome measure)
The primary outcome will be a composite of serious, adverse, patient-centered events, including death, need for acute dialysis, or persistent decline in kidney function. [ Time Frame: Within 90 days following angiography ] [ Designated as safety issue: No ]

Death will be based on medical record and/or vital status registry documentation

Need for acute dialysis will be defined as the initiation of any modality of renal replacement (intermittent hemodialysis, peritoneal dialysis, continuous renal replacement therapy, or sustained low-efficiency dialysis)

Persistent decline in kidney function will be defined as an increase in serum creatinine of at least 50% from the baseline value collected pre-angiography to the measurement taken 90 days following the angiography.

Same as current
Complete list of historical versions of study NCT01467466 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Prevention of Serious Adverse Events Following Angiography
CSP #578 - Prevention of Serious Adverse Events Following Angiography (PRESERVE)

The purpose of this research study is to compare the effectiveness of intravenous isotonic sodium bicarbonate with intravenous isotonic sodium chloride and oral N-acetylcysteine with oral placebo for the prevention of serious adverse outcomes following angiographic procedures in high-risk patients.

The intravascular administration of iodinated contrast media for diagnostic imaging is a common cause of acute kidney injury (AKI) and a leading cause of iatrogenic renal disease. Contrast-induced AKI is associated with serious adverse outcomes including death, need for dialysis, prolonged hospitalization, and acceleration in the rate of progression of underlying chronic kidney disease. The benefit of IV isotonic bicarbonate compared to IV isotonic saline and of N-acetylcysteine for the prevention of contrast-induced AKI and associated adverse outcomes remains unclear. The purpose of this trial is to compare the effectiveness of IV isotonic sodium bicarbonate with IV isotonic sodium chloride and oral NAC with placebo for the prevention of serious adverse outcomes in 8,680 high-risk patients scheduled to undergo coronary or non-coronary angiography. Using a 2 x 2 factorial design, patients will be randomized to receive: 1) either peri-procedural IV isotonic sodium bicarbonate or peri-procedural IV isotonic saline and 2) either oral NAC or oral placebo prior to and for 5 days following the angiographic procedure. The primary study endpoint is a composite outcome comprised of death, need for acute dialysis, or persistent decline in kidney function within 90 days following the index angiogram.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
  • Acute Renal Failure
  • Kidney Disease
  • Coronary Artery Disease
  • Drug: IV isotonic saline
    We will administer 3 ml/kg of isotonic saline over 1 hour at an infusion rate of not less than 1 mL/kg per hour and not more than 3 mL/kg per hour prior to the angiographic procedure, 1-1.5ml/kg per hour during angiography, and 6 ml/kg of isotonic saline over 4 hours following the procedure at an infusion rate of not less than 1 mL/kg per hour and not more than 1.5 mL/kg per hour. Providers will retain discretion to administer larger volumes of isotonic saline (up to a maximum of 12 mL/kg) over durations of up to 12 hours pre and 12 hours post-procedure.
  • Drug: IV isotonic bicarbonate
    We will administer 3 ml/kg of isotonic bicarbonate over 1 hour at an infusion rate of not less than 1 mL/kg per hour and not more than 3 mL/kg per hour prior to the angiographic procedure, 1-1.5ml/kg per hour during angiography, and 6 ml/kg of isotonic bicarbonate over 4 hours following the procedure at an infusion rate of not less than 1 mL/kg per hour and not more than 1.5 mL/kg per hour. Providers will retain discretion to administer larger volumes of isotonic bicarbonate (up to a maximum of 12 mL/kg) over durations of up to 12 hours pre and 12 hours post-procedure.
  • Drug: N-acetylcysteine
    NAC will be administered at a dose of 1200mg orally 1 hour prior to angiography, 1 hour following the procedure, and then twice daily for the next 4 days.
    Other Name: NAC
  • Drug: Placebo
    A placebo study drug capsule will be administered orally 1 hour prior to angiography, 1 hour following the procedure, and then twice daily for the next 4 days.
  • Active Comparator: Arm 1
    IV isotonic saline and oral placebo drug capsule
    Interventions:
    • Drug: IV isotonic saline
    • Drug: Placebo
  • Active Comparator: Arm 2
    IV isotonic saline and oral N-acetylcysteine drug capsule
    Interventions:
    • Drug: IV isotonic saline
    • Drug: N-acetylcysteine
  • Active Comparator: Arm 3
    IV isotonic bicarbonate and oral placebo drug capsule
    Interventions:
    • Drug: IV isotonic bicarbonate
    • Drug: Placebo
  • Active Comparator: Arm 4
    IV isotonic bicarbonate and oral N-acetylcysteine drug capsule
    Interventions:
    • Drug: IV isotonic bicarbonate
    • Drug: N-acetylcysteine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
8680
December 2016
March 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Planned elective or urgent coronary or non-coronary angiography with iodinated contrast media in which it is anticipated that there will be an interval of 3 hours between the identification of the indication for angiography and the time of the planned procedure.
  • Pre-angiography eGFR <60 ml/min/1.73 m2 with diabetes mellitus or pre-angiography eGFR <45 ml/min/1.73 m2 with or without diabetes mellitus
  • Ability to provide informed consent

Exclusion Criteria:

  • Stage 5 CKD (eGFR <15 mL/min/1.73 m2)
  • Currently receiving hemodialysis, peritoneal dialysis, continuous renal replacement therapy, or sustained low efficiency dialysis (SLED)
  • Unstable baseline SCr (if known) at the time of angiography defined by an increase in SCr of 25% over the 3 days prior to angiography
  • Decompensated heart failure requiring any of the following therapies at the time of angiography:

    • IV milrinone, amrinone, dobutamine, or nesiritide
    • Isolated ultrafiltration therapy
    • Intra-aortic balloon pump
  • Emergent angiography procedures defined as an anticipated duration of <3 hours between the identification of the indication for angiography and the time of the planned procedure.
  • Receipt of intravascular iodinated contrast within the 5 days preceding angiography
  • Receipt of oral or IV NAC within the 48 hours preceding angiography
  • Known allergy to N-acetylcysteine (NAC)
  • Known anaphylactic allergy to iodinated contrast media
  • Prisoner
  • Age <18 years
  • Pregnancy
  • Ongoing participation in an unapproved concurrent interventional study
Both
18 Years and older
No
Contact: James S Kaufman, MD (212) 686-7500 ext 7470 james.kaufman@va.gov
Contact: Kandarp Mehta, MS (857) 364-4837 kandarp.mehta2@va.gov
United States,   Australia
 
NCT01467466
578, 1011387
Yes
Department of Veterans Affairs
Department of Veterans Affairs
The George Institute
Study Chair: Steven D. Weisbord, MD MSc VA Pittsburgh Healthcare System
Department of Veterans Affairs
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP