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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01467466
Other study ID # 578
Secondary ID 1011387
Status Completed
Phase Phase 3
First received
Last updated
Start date October 7, 2013
Est. completion date October 17, 2017

Study information

Verified date September 2022
Source VA Office of Research and Development
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 5177
Est. completion date October 17, 2017
Est. primary completion date September 29, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

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.
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.
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.
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.

Locations

Country Name City State
Australia Flinders Medical Centre Bedford Park South Australia
Australia Canberra Hospital Canberra Australian Capital Territory
Australia Concord Hospital Concord New South Wales
Australia Northern Health Epping Victoria
Australia Fremantle Hospital Fremantle Western Australia
Australia Gosford Hospital Gosford New South Wales
Australia Austin Health Heidelberg Victoria
Australia Nepean Hospital Kingswood New South Wales
Australia St. George Hospital Kogarah New South Wales
Australia Liverpool Hospital Liverpool New South Wales
Australia Sir Charles Gairdner Hospital Nedlands Western Australia
Australia Royal Perth Hospital Perth Western Australia
Australia Royal North Shore Hospital St. Leonards New South Wales
Malaysia Penang Hospital George Town Penang
Malaysia University of Malaya Medical Center Kuala Lumpur
Malaysia Hospital Serdang Sepang Selangor
New Zealand Auckland City Hospital Auckland
New Zealand Wellington Hospital Newtown Wellington
New Zealand Taranaki Base Hospital Westown New Plymouth
United States New Mexico VA Health Care System, Albuquerque, NM Albuquerque New Mexico
United States VA Ann Arbor Healthcare System, Ann Arbor, MI Ann Arbor Michigan
United States Charlie Norwood VA Medical Center, Augusta, GA Augusta Georgia
United States Bay Pines VA Healthcare System, Pay Pines, FL Bay Pines Florida
United States VA Western New York Healthcare System, Buffalo, NY Buffalo New York
United States Ralph H. Johnson VA Medical Center, Charleston, SC Charleston South Carolina
United States Jesse Brown VA Medical Center, Chicago, IL Chicago Illinois
United States Cincinnati VA Medical Center, Cincinnati, OH Cincinnati Ohio
United States Louis Stokes VA Medical Center, Cleveland, OH Cleveland Ohio
United States VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX Dallas Texas
United States Dayton VA Medical Center, Dayton, OH Dayton Ohio
United States Atlanta VA Medical and Rehab Center, Decatur, GA Decatur Georgia
United States Durham VA Medical Center, Durham, NC Durham North Carolina
United States North Florida/South Georgia Veterans Health System, Gainesville, FL Gainesville Florida
United States Michael E. DeBakey VA Medical Center, Houston, TX Houston Texas
United States Richard L. Roudebush VA Medical Center, Indianapolis, IN Indianapolis Indiana
United States Kansas City VA Medical Center, Kansas City, MO Kansas City Missouri
United States Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR Little Rock Arkansas
United States Memphis VA Medical Center, Memphis, TN Memphis Tennessee
United States Minneapolis VA Health Care System, Minneapolis, MN Minneapolis Minnesota
United States Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY New York New York
United States Oklahoma City VA Medical Center, Oklahoma City, OK Oklahoma City Oklahoma
United States VA Palo Alto Health Care System, Palo Alto, CA Palo Alto California
United States VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA Pittsburgh Pennsylvania
United States Portland VA Medical Center, Portland, OR Portland Oregon
United States Hunter Holmes McGuire VA Medical Center, Richmond, VA Richmond Virginia
United States St. Louis VA Medical Center John Cochran Division, St. Louis, MO Saint Louis Missouri
United States Salem VA Medical Center, Salem, VA Salem Virginia
United States VA Salt Lake City Health Care System, Salt Lake City, UT Salt Lake City Utah
United States South Texas Health Care System, San Antonio, TX San Antonio Texas
United States San Francisco VA Medical Center, San Francisco, CA San Francisco California
United States VA Puget Sound Health Care System Seattle Division, Seattle, WA Seattle Washington
United States Southern Arizona VA Health Care System, Tucson Tucson Arizona
United States VA Greater Los Angeles Healthcare System, West Los Angeles, CA West Los Angeles California
United States VA Boston Healthcare System West Roxbury Campus, West Roxbury, MA West Roxbury Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
VA Office of Research and Development The George Institute

Countries where clinical trial is conducted

United States,  Australia,  Malaysia,  New Zealand, 

References & Publications (5)

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):4 — View 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 PRES — View 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/ — View Citation

Soomro QH, Anand ST, Weisbord SD, Gallagher MP, Ferguson RE, Palevsky PM, Bhatt DL, Parikh CR, Kaufman JS; PRESERVE Trial Investigators. The Relationship between Rate and Volume of Intravenous Fluid Administration and Kidney Outcomes after Angiography. Cl — View 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 — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 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
Primary 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. 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
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