Prevention of Serious Adverse Events Following Angiography (PRESERVE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 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: April 30, 2014
Last verified: April 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 Outcomes Following Angiography

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:

  • ESRD requiring chronic renal replacement therapy
  • Stage 5 CKD (eGFR <15 mL/min/1.73 m2)
  • Acute kidney injury requiring intermittent hemodialysis or continuous renal replacement therapy at the time of angiography
  • 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 7 days preceding angiography
  • Receipt of oral or IV NAC within the 48 hours preceding angiography
  • Known allergy to N-acetylcysteine (NAC)
  • Known allergy to iodinated contrast media
  • Prisoner
  • Age <18 years
  • Pregnancy
  • Ongoing participation in a 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: Clara E Kebabian (857) 364-6026 clara.kebabian@va.gov

  Hide Study Locations
Locations
United States, Arizona
Southern Arizona VA Health Care System, Tucson Recruiting
Tucson, Arizona, United States, 85723
Contact: Hoang Thai, MD    520-792-1450 ext 5151    hoang.thai@va.gov   
United States, Arkansas
Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR Recruiting
Little Rock, Arkansas, United States, 72205-5484
Contact: Rajesh Sachdeva, MBBS    501-257-5795    rajesh.sachdeva@va.gov   
United States, California
VA Palo Alto Health Care System, Palo Alto, CA Recruiting
Palo Alto, California, United States, 94304-1290
Contact: John Giacomini, MD    650-858-3932    john.giacomini@va.gov   
San Francisco VA Medical Center, San Francisco, CA Recruiting
San Francisco, California, United States, 94121
Contact: Kendrick Shunk, MD    415-750-2076    kendrick.shunk@va.gov   
VA Greater Los Angeles Healthcare System, West Los Angeles, CA Recruiting
West Los Angeles, California, United States, 90073
Contact: Jessie W Currier, MD    310-268-4695    jesse.currier@va.gov   
United States, Florida
Bay Pines VA Healthcare System, Pay Pines, FL Recruiting
Bay Pines, Florida, United States, 33708
Contact: Mazhar A Afaq, MD    727-398-6661 ext 5279, 4234    mazhar.afaq@va.gov   
North Florida/South Georgia Veterans Health System, Gainesville, FL Recruiting
Gainesville, Florida, United States, 32608
Contact: Anthony Bavry, MD       anthony.bavry@va.gov   
United States, Georgia
Charlie Norwood VA Medical Center, Augusta, GA Recruiting
Augusta, Georgia, United States, 30904
Contact: Mahendra K Mandawat, MD    706-823-3902    mahendra.mandawat@va.gov   
Atlanta VA Medical and Rehab Center, Decatur, GA Recruiting
Decatur, Georgia, United States, 30033
Contact: Kreton Mavromatis, MD    404-329-2207    kreton.mavromatis@va.gov   
United States, Illinois
Jesse Brown VA Medical Center, Chicago, IL Recruiting
Chicago, Illinois, United States, 60612
Contact: Mladen Vidovich, MD    312-996-6730    mladen.vidovich@va.gov   
United States, Indiana
Richard L. Roudebush VA Medical Center, Indianapolis, IN Recruiting
Indianapolis, Indiana, United States, 46202-2884
Contact: Islam Bolad, MD    317-988-2093    islam.bolad@va.gov   
United States, Massachusetts
VA Boston Healthcare System West Roxbury Campus, West Roxbury, MA Recruiting
West Roxbury, Massachusetts, United States, 02132
Contact: Scott Kinlay, MBBS    857-203-5550    scott.kinlay@va.gov   
United States, Michigan
VA Ann Arbor Healthcare System, Ann Arbor, MI Recruiting
Ann Arbor, Michigan, United States, 48113
Contact: Claire Duvernoy, MD    734-845-5531    claire.duvernoy@va.gov   
United States, Minnesota
Minneapolis VA Health Care System, Minneapolis, MN Recruiting
Minneapolis, Minnesota, United States, 55417
Contact: Edward McFalls, MD    612-725-2000 ext 3664    edward.mcfalls@va.gov   
United States, Missouri
Kansas City VA Medical Center, Kansas City, MO Recruiting
Kansas City, Missouri, United States, 64128
Contact: Deepak Parashara, MD    816-861-4700 ext 52475    deepak.parashara@va.gov   
St. Louis VA Medical Center John Cochran Division, St. Louis, MO Recruiting
St Louis, Missouri, United States, 63106
Contact: Andrew Klein, MD    314-652-4100 ext 6329    andrew.klein3@va.gov   
United States, New Mexico
New Mexico VA Health Care System, Albuquerque, NM Recruiting
Albuquerque, New Mexico, United States, 87108-5153
Contact: D. Michelle Ratliff, MD    505-265-1711 ext 4494    michelle.ratliff@va.gov   
United States, New York
Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY Recruiting
New York, New York, United States, 10010
Contact: Steven Sedlis, MD    212-951-3335    steven.sedlis@va.gov   
United States, North Carolina
Durham VA Medical Center, Durham, NC Recruiting
Durham, North Carolina, United States, 27705
Contact: Sunil Rao, MD    919-684-8111    sunil.rao@va.gov   
United States, Ohio
Cincinnati VA Medical Center, Cincinnati, OH Recruiting
Cincinnati, Ohio, United States, 45220
Contact: Florence Rothenberg, MD    513-861-3100    florence.rothenberg@va.gov   
Louis Stokes VA Medical Center, Cleveland, OH Recruiting
Cleveland, Ohio, United States, 44106
Contact: Jonathan Goldberg, MD    216-791-3800 ext 4934    jonathan.goldberg@va.gov   
Dayton VA Medical Center, Dayton, OH Recruiting
Dayton, Ohio, United States, 45428
Contact: Ajay Agarwal, MD    937-262-2113    ajay.agarwal@va.gov   
United States, Oklahoma
Oklahoma City VA Medical Center, Oklahoma City, OK Not yet recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Mazen Abu-Fadel, MD    405-456-5378    mazen.abu-fadel@va.gov   
United States, Oregon
Portland VA Medical Center, Portland, OR Recruiting
Portland, Oregon, United States, 97201
Contact: Greg Larsen, MD    503-220-8262 ext 55632    greg.larsen@va.gov   
United States, Pennsylvania
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA Recruiting
Pittsburgh, Pennsylvania, United States, 15240
Contact: Steven D Weisbord, MD MSc    412-360-3911    steven.weisbord@va.gov   
Contact: Paul M Palevsky    (412) 688-6000 ext 815932    Paul.Palevsky@va.gov   
Study Chair: Steven D. Weisbord, MD MSc         
United States, South Carolina
Ralph H. Johnson VA Medical Center, Charleston, SC Recruiting
Charleston, South Carolina, United States, 29401-5799
Contact: Valerian L Fernandes, MD    843-789-7594 ext 7294    valerian.fernandes@va.gov   
United States, Tennessee
Memphis VA Medical Center, Memphis, TN Recruiting
Memphis, Tennessee, United States, 38104
Contact: Kodangudi B Ramanathan, MD    901-523-8990 ext 7355    kodangudi.ramanathan@va.gov   
United States, Texas
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX Recruiting
Dallas, Texas, United States, 75216
Contact: Emmanouil Brilakis, MD    214-857-1547    emmanouil.brilakis@va.gov   
Michael E. DeBakey VA Medical Center, Houston, TX Recruiting
Houston, Texas, United States, 77030
Contact: Hani Jneid, MD    713-794-7300 ext 7823    mohammad.jneid@va.gov   
South Texas Health Care System, San Antonio, TX Recruiting
San Antonio, Texas, United States, 78229
Contact: Robert J Chilton, DO    210-617-5300    robert.chilton@va.gov   
United States, Virginia
Hunter Holmes McGuire VA Medical Center, Richmond, VA Recruiting
Richmond, Virginia, United States, 23249
Contact: Ion S Jovin, MD    804-675-5448    ion.jovin@va.gov   
Salem VA Medical Center, Salem, VA Recruiting
Salem, Virginia, United States, 24153
Contact: Venkata S Chilakapati, MD    540-982-2463 ext 2568    venkata.chilakapati2@va.gov   
United States, Washington
VA Puget Sound Health Care System Seattle Division, Seattle, WA Recruiting
Seattle, Washington, United States, 98108
Contact: Kenneth Lehmann, MD    206-764-2512    kenneth.lehmann@va.gov   
Australia, New South Wales
Concord Hospital Recruiting
Concord, New South Wales, Australia, 2139
Contact: David Brieger       davidb@email.cs.nsw.gov.au   
Gosford Hospital Recruiting
Gosford, New South Wales, Australia, 2250
Contact: Maged William       mwwilliam@nsccahs.health.nsw.gov.au   
Nepean Hospital Recruiting
Kingswood, New South Wales, Australia, 2747
Contact: Hisham Hallani       Hisham.Hallani@swahs.health.nsw.gov.au   
St. George Hospital Recruiting
Kogarah, New South Wales, Australia, 2217
Contact: Ananth Prasan       ananth.prasan@sesiahs.health.nsw.gov.au   
Liverpool Hospital Recruiting
Liverpool, New South Wales, Australia, 2170
Contact: Craig Juergens       c.juergens@unsw.edu.au   
Royal North Shore Hospital Recruiting
St. Leonards, New South Wales, Australia, 2065
Contact: Gregory Nelson       gnelson@med.usyd.edu.au   
Australia, South Australia
Flinders Medical Centre Recruiting
Bedford Park, South Australia, Australia, 5042
Contact: Derek Chew       derek.chew@flinders.edu.au   
Australia, Victoria
Northern Health Recruiting
Epping, Victoria, Australia, 3076
Contact: William VanGaal       william.vangaal@nh.org.au   
Austin Health Recruiting
Heidelberg, Victoria, Australia, 3084
Contact: Omar Farouque       omar.farouque@austin.org.au   
Australia, Western Australia
Fremantle Hospital Recruiting
Fremantle, Western Australia, Australia, 6160
Contact: Randall Hendriks       rh@coastal-cardiology.com.au   
Sir Charles Gairdner Hospital Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Joseph Hung       joseph.hung@health.wa.gov.au   
Royal Perth Hospital Recruiting
Perth, Western Australia, Australia, 6000
Contact: Matthew Erickson       exiterickson@mac.com   
Sponsors and Collaborators
The George Institute
Investigators
Study Chair: Steven D. Weisbord, MD MSc VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
  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: April 30, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
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
Acute Kidney Injury
Renal Insufficiency
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Urologic Diseases
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on August 01, 2014