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Prevention of Serious Adverse Events Following Angiography (PRESERVE)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01467466
First Posted: November 8, 2011
Last Update Posted: November 23, 2017
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.
Collaborator:
The George Institute
Information provided by (Responsible Party):
VA Office of Research and Development
  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
Intervention Model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: CSP #578 - Prevention of Serious Adverse Events Following Angiography (PRESERVE)

Further study details as provided by VA Office of Research and Development:

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 ]

    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.



Enrollment: 5183
Actual Study Start Date: February 7, 2013
Study Completion Date: September 29, 2017
Primary Completion Date: September 29, 2017 (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
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: Arm 2
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 Name: NAC
Active Comparator: Arm 3
IV isotonic bicarbonate and oral placebo drug capsule
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: 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
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

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.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01467466


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

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT01467466     History of Changes
Other Study ID Numbers: 578
1011387 ( Other Grant/Funding Number: National Health and Medical Research Council )
First Submitted: October 26, 2011
First Posted: November 8, 2011
Last Update Posted: November 23, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Keywords provided by VA Office of Research and Development:
renal
cardiovascular
kidney
heart
clinical trial
double-blind
multi-site trial
randomized
drug treatment
IV solutions
antioxidant

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