Prevention of Serious Adverse Events Following Angiography

Coronary Artery Disease Clinical Trial

— PRESERVE  

Official title:

CSP #578 - Prevention of Serious Adverse Events Following Angiography (PRESERVE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01467466
• Other study ID #: 578
• Secondary ID: 1011387
• Status: Completed
• Phase: Phase 3
• 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
• 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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute Renal Failure
• Coronary Artery Disease
• Kidney Disease
• Kidney Diseases

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