Prevention of Serious Adverse Events Following Angiography (PRESERVE)

September 21, 2022 updated by: VA Office of Research and Development

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 (NAC) with oral placebo for the prevention of serious adverse outcomes following angiographic procedures in high-risk patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

5177

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Australian Capital Territory
      • Canberra, Australian Capital Territory, Australia, 2606
        • Canberra Hospital
    • New South Wales
      • Concord, New South Wales, Australia, 2139
        • Concord Hospital
      • Gosford, New South Wales, Australia, 2250
        • Gosford Hospital
      • Kingswood, New South Wales, Australia, 2747
        • Nepean Hospital
      • Kogarah, New South Wales, Australia, 2217
        • St. George Hospital
      • Liverpool, New South Wales, Australia, 2170
        • Liverpool Hospital
      • St. Leonards, New South Wales, Australia, 2065
        • Royal North Shore Hospital
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Flinders Medical Centre
    • Victoria
      • Epping, Victoria, Australia, 3076
        • Northern Health
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health
    • Western Australia
      • Fremantle, Western Australia, Australia, 6160
        • Fremantle Hospital
      • Nedlands, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital
      • Perth, Western Australia, Australia, 6000
        • Royal Perth Hospital
  • Malaysia
      • Kuala Lumpur, Malaysia, 50603
        • University of Malaya Medical Center
    • Penang
      • George Town, Penang, Malaysia, 10990
        • Penang Hospital
    • Selangor
      • Sepang, Selangor, Malaysia, 43300
        • Hospital Serdang
  • New Zealand
      • Auckland, New Zealand, 1142
        • Auckland City Hospital
    • New Plymouth
      • Westown, New Plymouth, New Zealand, 4310
        • Taranaki Base Hospital
    • Wellington
      • Newtown, Wellington, New Zealand, 1142
        • Wellington Hospital
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85723
        • Southern Arizona VA Health Care System, Tucson
    • Arkansas
      • Little Rock, Arkansas, United States, 72205-5484
        • Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR
    • California
      • Palo Alto, California, United States, 94304-1290
        • VA Palo Alto Health Care System, Palo Alto, CA
      • San Francisco, California, United States, 94121
        • San Francisco VA Medical Center, San Francisco, CA
      • West Los Angeles, California, United States, 90073
        • VA Greater Los Angeles Healthcare System, West Los Angeles, CA
    • Florida
      • Bay Pines, Florida, United States, 33708
        • Bay Pines VA Healthcare System, Pay Pines, FL
      • Gainesville, Florida, United States, 32608
        • North Florida/South Georgia Veterans Health System, Gainesville, FL
    • Georgia
      • Augusta, Georgia, United States, 30904
        • Charlie Norwood VA Medical Center, Augusta, GA
      • Decatur, Georgia, United States, 30033
        • Atlanta VA Medical and Rehab Center, Decatur, GA
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Jesse Brown VA Medical Center, Chicago, IL
    • Indiana
      • Indianapolis, Indiana, United States, 46202-2884
        • Richard L. Roudebush VA Medical Center, Indianapolis, IN
    • Massachusetts
      • West Roxbury, Massachusetts, United States, 02132
        • VA Boston Healthcare System West Roxbury Campus, West Roxbury, MA
    • Michigan
      • Ann Arbor, Michigan, United States, 48113
        • VA Ann Arbor Healthcare System, Ann Arbor, MI
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417
        • Minneapolis VA Health Care System, Minneapolis, MN
    • Missouri
      • Kansas City, Missouri, United States, 64128
        • Kansas City VA Medical Center, Kansas City, MO
      • Saint Louis, Missouri, United States, 63106
        • St. Louis VA Medical Center John Cochran Division, St. Louis, MO
    • New Mexico
      • Albuquerque, New Mexico, United States, 87108-5153
        • New Mexico VA Health Care System, Albuquerque, NM
    • New York
      • Buffalo, New York, United States, 14215
        • VA Western New York Healthcare System, Buffalo, NY
      • New York, New York, United States, 10010
        • Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Durham VA Medical Center, Durham, NC
    • Ohio
      • Cincinnati, Ohio, United States, 45220
        • Cincinnati VA Medical Center, Cincinnati, OH
      • Cleveland, Ohio, United States, 44106
        • Louis Stokes VA Medical Center, Cleveland, OH
      • Dayton, Ohio, United States, 45428
        • Dayton VA Medical Center, Dayton, OH
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma City VA Medical Center, Oklahoma City, OK
    • Oregon
      • Portland, Oregon, United States, 97201
        • Portland VA Medical Center, Portland, OR
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15240
        • VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
    • South Carolina
      • Charleston, South Carolina, United States, 29401-5799
        • Ralph H. Johnson VA Medical Center, Charleston, SC
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • Memphis VA Medical Center, Memphis, TN
    • Texas
      • Dallas, Texas, United States, 75216
        • VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
      • Houston, Texas, United States, 77030
        • Michael E. DeBakey VA Medical Center, Houston, TX
      • San Antonio, Texas, United States, 78229
        • South Texas Health Care System, San Antonio, TX
    • Utah
      • Salt Lake City, Utah, United States, 84148
        • VA Salt Lake City Health Care System, Salt Lake City, UT
    • Virginia
      • Richmond, Virginia, United States, 23249
        • Hunter Holmes McGuire VA Medical Center, Richmond, VA
      • Salem, Virginia, United States, 24153
        • Salem VA Medical Center, Salem, VA
    • Washington
      • Seattle, Washington, United States, 98108
        • VA Puget Sound Health Care System Seattle Division, Seattle, WA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: FACTORIAL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Saline & oral placebo
IV isotonic saline and oral placebo drug capsule
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: 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: Saline & oral N-acetylcysteine
IV isotonic saline and oral N-acetylcysteine drug capsule
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: 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 Names:
  • NAC
ACTIVE_COMPARATOR: Bicarbonate & oral placebo
IV isotonic bicarbonate and oral placebo drug capsule
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.
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.
ACTIVE_COMPARATOR: Bicarbonate & oral N-acetylcysteine
IV isotonic bicarbonate and oral N-acetylcysteine drug capsule
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 Names:
  • NAC
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Within 90 days following 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.
Within 90 days following angiography

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Collaborators

The George Institute

Investigators

  • Study Chair: Steven D. Weisbord, MD MSc, VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 7, 2013

Primary Completion (ACTUAL)

September 29, 2017

Study Completion (ACTUAL)

October 17, 2017

Study Registration Dates

First Submitted

October 26, 2011

First Submitted That Met QC Criteria

November 3, 2011

First Posted (ESTIMATE)

November 8, 2011

Study Record Updates

Last Update Posted (ACTUAL)

October 3, 2022

Last Update Submitted That Met QC Criteria

September 21, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 578
  • 1011387 (OTHER_GRANT: National Health and Medical Research Council)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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