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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
  Purpose

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.


Condition Intervention Phase
Acute Renal Failure
Kidney Disease
Coronary Artery Disease
Drug: IV isotonic saline
Drug: IV isotonic bicarbonate
Drug: N-acetylcysteine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: CSP #578 - Prevention of Serious Adverse Events Following Angiography (PRESERVE)

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • 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.



Estimated Enrollment: 8680
Study Start Date: February 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
IV isotonic saline and oral placebo drug capsule
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: 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 2
IV isotonic saline and oral N-acetylcysteine drug capsule
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: 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
Active Comparator: Arm 3
IV isotonic bicarbonate and oral placebo drug capsule
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: 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 4
IV isotonic bicarbonate and oral N-acetylcysteine drug capsule
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

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01467466

Contacts
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

  Show 45 Study Locations
Sponsors and Collaborators
The George Institute
Investigators
Study Chair: Steven D. Weisbord, MD MSc VA Pittsburgh Healthcare System
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01467466     History of Changes
Other Study ID Numbers: 578, 1011387
Study First Received: October 26, 2011
Last Updated: September 19, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
heart
renal
cardiovascular
kidney
clinical trial
double-blind
multi-site trial
randomized
drug treatment
IV solutions
antioxidant

Additional relevant MeSH terms:
Coronary Artery Disease
Coronary Disease
Heart Diseases
Acute Kidney Injury
Kidney Diseases
Myocardial Ischemia
Renal Insufficiency
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Urologic Diseases
Vascular Diseases
Acetylcysteine
N-monoacetylcystine
Anti-Infective Agents
Antidotes
Antioxidants
Antiviral Agents
Expectorants
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014