Clinical trial NCT01467466: Prevention of Serious Adverse Events Following Angiography
Official title: CSP #578 - Prevention of Serious Adverse Events Following Angiography (PRESERVE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Renal Failure
Kidney Disease
Coronary Artery Disease
Keywords: renal
cardiovascular
kidney
heart
clinical trial
double-blind
multi-site trial
randomized
drug treatment
IV solutions
antioxidant
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: The George Institute
First posted: 2011-11-08
Enrollment: 5177
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.

Eligibility 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 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

Primary outcomes:
measure: 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.
timeFrame: Within 90 days following angiography
measure: 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.
timeFrame: Within 90 days following angiography
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Southern Arizona VA Health Care System, Tucson
state: Arizona
city: Little Rock
country: United States
facility: Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR
state: Arkansas
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System, Palo Alto, CA
state: California
city: San Francisco
country: United States
facility: San Francisco VA Medical Center, San Francisco, CA
state: California
city: West Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
state: California
city: Bay Pines
country: United States
facility: Bay Pines VA Healthcare System, Pay Pines, FL
state: Florida
city: Gainesville
country: United States
facility: North Florida/South Georgia Veterans Health System, Gainesville, FL
state: Florida
city: Augusta
country: United States
facility: Charlie Norwood VA Medical Center, Augusta, GA
state: Georgia
city: Decatur
country: United States
facility: Atlanta VA Medical and Rehab Center, Decatur, GA
state: Georgia
city: Chicago
country: United States
facility: Jesse Brown VA Medical Center, Chicago, IL
state: Illinois
city: Indianapolis
country: United States
facility: Richard L. Roudebush VA Medical Center, Indianapolis, IN
state: Indiana
city: West Roxbury
country: United States
facility: VA Boston Healthcare System West Roxbury Campus, West Roxbury, MA
state: Massachusetts
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System, Ann Arbor, MI
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System, Minneapolis, MN
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City VA Medical Center, Kansas City, MO
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis VA Medical Center John Cochran Division, St. Louis, MO
state: Missouri
city: Albuquerque
country: United States
facility: New Mexico VA Health Care System, Albuquerque, NM
state: New Mexico
city: Buffalo
country: United States
facility: VA Western New York Healthcare System, Buffalo, NY
state: New York
city: New York
country: United States
facility: Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
state: New York
city: Durham
country: United States
facility: Durham VA Medical Center, Durham, NC
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati VA Medical Center, Cincinnati, OH
state: Ohio
city: Cleveland
country: United States
facility: Louis Stokes VA Medical Center, Cleveland, OH
state: Ohio
city: Dayton
country: United States
facility: Dayton VA Medical Center, Dayton, OH
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma City VA Medical Center, Oklahoma City, OK
state: Oklahoma
city: Portland
country: United States
facility: Portland VA Medical Center, Portland, OR
state: Oregon
city: Pittsburgh
country: United States
facility: VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
state: Pennsylvania
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center, Charleston, SC
state: South Carolina
city: Memphis
country: United States
facility: Memphis VA Medical Center, Memphis, TN
state: Tennessee
city: Dallas
country: United States
facility: VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center, Houston, TX
state: Texas
city: San Antonio
country: United States
facility: South Texas Health Care System, San Antonio, TX
state: Texas
city: Salt Lake City
country: United States
facility: VA Salt Lake City Health Care System, Salt Lake City, UT
state: Utah
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center, Richmond, VA
state: Virginia
city: Salem
country: United States
facility: Salem VA Medical Center, Salem, VA
state: Virginia
city: Seattle
country: United States
facility: VA Puget Sound Health Care System Seattle Division, Seattle, WA
state: Washington
city: Canberra
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Concord
country: Australia
facility: Concord Hospital
state: New South Wales
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: St. George Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Epping
country: Australia
facility: Northern Health
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Fremantle
country: Australia
facility: Fremantle Hospital
state: Western Australia
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: George Town
country: Malaysia
facility: Penang Hospital
state: Penang
city: Sepang
country: Malaysia
facility: Hospital Serdang
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Center
city: Westown
country: New Zealand
facility: Taranaki Base Hospital
state: New Plymouth
city: Newtown
country: New Zealand
facility: Wellington Hospital
state: Wellington
city: Auckland
country: New Zealand
facility: Auckland City Hospital
Study officials:
affiliation: VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
name: Steven D. Weisbord, MD MSc
role: STUDY_CHAIR
References:
citation: Garcia S, Bhatt DL, Gallagher M, Jneid H, Kaufman J, Palevsky PM, Wu H, Weisbord SD; PRESERVE Trial Group. Strategies to Reduce Acute Kidney Injury and Improve Clinical Outcomes Following Percutaneous Coronary Intervention: A Subgroup Analysis of the PRESERVE Trial. JACC Cardiovasc Interv. 2018 Nov 26;11(22):2254-2261. doi: 10.1016/j.jcin.2018.07.044.
citation: Parikh CR, Liu C, Mor MK, Palevsky PM, Kaufman JS, Thiessen Philbrook H, Weisbord SD. Kidney Biomarkers of Injury and Repair as Predictors of Contrast-Associated AKI: A Substudy of the PRESERVE Trial. Am J Kidney Dis. 2020 Feb;75(2):187-194. doi: 10.1053/j.ajkd.2019.06.011. Epub 2019 Sep 20.
citation: Weisbord SD, Palevsky PM, Kaufman JS, Wu H, Androsenko M, Ferguson RE, Parikh CR, Bhatt DL, Gallagher M; PRESERVE Trial Investigators. Contrast-Associated Acute Kidney Injury and Serious Adverse Outcomes Following Angiography. J Am Coll Cardiol. 2020 Mar 24;75(11):1311-1320. doi: 10.1016/j.jacc.2020.01.023.
citation: Bullen AL, Cashion W, Webster L, Palevsky PM, Weisbord SD, Ix JH. Estimated Urinary Flow Rate and Contrast-Associated Acute Kidney Injury Risk: The PRESERVE (Prevention of Serious Adverse Events Following Angiography) Trial. Kidney Med. 2021 Feb 27;3(3):461-463. doi: 10.1016/j.xkme.2020.12.014. eCollection 2021 May-Jun. No abstract available.
citation: Soomro QH, Anand ST, Weisbord SD, Gallagher MP, Ferguson RE, Palevsky PM, Bhatt DL, Parikh CR, Kaufman JS; PRESERVE Trial Investigators; PRESERVE Trial Group. The Relationship between Rate and Volume of Intravenous Fluid Administration and Kidney Outcomes after Angiography. Clin J Am Soc Nephrol. 2022 Oct;17(10):1446-1456. doi: 10.2215/CJN.02160222. Epub 2022 Aug 25.
citation: Weisbord SD, Gallagher M, Jneid H, Garcia S, Cass A, Thwin SS, Conner TA, Chertow GM, Bhatt DL, Shunk K, Parikh CR, McFalls EO, Brophy M, Ferguson R, Wu H, Androsenko M, Myles J, Kaufman J, Palevsky PM; PRESERVE Trial Group. Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine. N Engl J Med. 2018 Feb 15;378(7):603-614. doi: 10.1056/NEJMoa1710933. Epub 2017 Nov 12.