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Prevention of Serious Adverse Events Following Angiography (PRESERVE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01467466
Recruitment Status : Completed
First Posted : November 8, 2011
Results First Posted : November 9, 2018
Last Update Posted : May 5, 2020
Sponsor:
Collaborator:
The George Institute
Information provided by (Responsible Party):
VA Office of Research and Development

Tracking Information
First Submitted Date  ICMJE October 26, 2011
First Posted Date  ICMJE November 8, 2011
Results First Submitted Date  ICMJE October 2, 2018
Results First Posted Date  ICMJE November 9, 2018
Last Update Posted Date May 5, 2020
Actual Study Start Date  ICMJE October 7, 2013
Actual Primary Completion Date September 29, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 6, 2018)
  • Number of Participants With Serious, Adverse, Patient-Centered Events, Including Death, Need for Acute Dialysis, or Persistent Decline in Kidney Function, Comparing Intravenous Sodium Bicarbonate With Intravenous Sodium Chloride. [ Time Frame: Within 90 days following angiography ]
    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.
  • Number of Participants With Serious, Adverse, Patient-Centered Events, Including Death, Need for Acute Dialysis, or Persistent Decline in Kidney Function, Comparing Oral N-Acetylcysteine With Oral Placebo. [ Time Frame: Within 90 days following angiography ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 3, 2011)
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 ]
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.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prevention of Serious Adverse Events Following Angiography
Official Title  ICMJE CSP #578 - Prevention of Serious Adverse Events Following Angiography (PRESERVE)
Brief Summary 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 (NAC) with oral placebo for the prevention of serious adverse outcomes following angiographic procedures in high-risk patients.
Detailed Description 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 7,680 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE
  • Acute Renal Failure
  • Kidney Disease
  • Coronary Artery Disease
Intervention  ICMJE
  • Drug: IV isotonic saline
    The investigators 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
    The investigators 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.
Study Arms  ICMJE
  • Active Comparator: Saline & oral placebo
    IV isotonic saline and oral placebo drug capsule
    Interventions:
    • Drug: IV isotonic saline
    • Drug: Placebo
  • Active Comparator: Saline & oral N-acetylcysteine
    IV isotonic saline and oral N-acetylcysteine drug capsule
    Interventions:
    • Drug: IV isotonic saline
    • Drug: N-acetylcysteine
  • Active Comparator: Bicarbonate & oral placebo
    IV isotonic bicarbonate and oral placebo drug capsule
    Interventions:
    • Drug: IV isotonic bicarbonate
    • Drug: Placebo
  • Active Comparator: Bicarbonate & oral N-acetylcysteine
    IV isotonic bicarbonate and oral N-acetylcysteine drug capsule
    Interventions:
    • Drug: IV isotonic bicarbonate
    • Drug: N-acetylcysteine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 6, 2018)
5177
Original Estimated Enrollment  ICMJE
 (submitted: November 3, 2011)
8680
Actual Study Completion Date  ICMJE October 17, 2017
Actual Primary Completion Date September 29, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 chronic kidney disease (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 serum creatinine (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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Malaysia,   New Zealand,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01467466
Other Study ID Numbers  ICMJE 578
1011387 ( Other Grant/Funding Number: National Health and Medical Research Council )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party VA Office of Research and Development
Study Sponsor  ICMJE VA Office of Research and Development
Collaborators  ICMJE The George Institute
Investigators  ICMJE
Study Chair: Steven D. Weisbord, MD MSc VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
PRS Account VA Office of Research and Development
Verification Date April 2020

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