Prevention of Serious Adverse Events Following Angiography

NCT ID: NCT01467466

Last Updated: 2025-11-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 5177 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-07
• Study Completion Date: 2017-10-17

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.

Conditions

Acute Renal Failure; Kidney Disease; Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Saline & oral placebo

IV isotonic saline and oral placebo drug capsule

Group Type: ACTIVE_COMPARATOR

IV isotonic saline

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

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.

Saline & oral N-acetylcysteine

IV isotonic saline and oral N-acetylcysteine drug capsule

Group Type: ACTIVE_COMPARATOR

IV isotonic saline

Intervention Type: DRUG

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.

N-acetylcysteine

Intervention Type: DRUG

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.

Bicarbonate & oral placebo

IV isotonic bicarbonate and oral placebo drug capsule

Group Type: ACTIVE_COMPARATOR

IV isotonic bicarbonate

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

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.

Bicarbonate & oral N-acetylcysteine

IV isotonic bicarbonate and oral N-acetylcysteine drug capsule

Group Type: ACTIVE_COMPARATOR

IV isotonic bicarbonate

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

NAC

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The George Institute

OTHER

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven D. Weisbord, MD MSc

Role: STUDY_CHAIR

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Locations

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, United States

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, United States

Kansas City VA Medical Center, Kansas City, MO

Kansas City, Missouri, United States

St. Louis VA Medical Center John Cochran Division, St. Louis, MO

St Louis, Missouri, United States

VA Western New York Healthcare System, Buffalo, NY

Buffalo, New York, United States

Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY

New York, New York, United States

Durham VA Medical Center, Durham, NC

Durham, North Carolina, United States

Cincinnati VA Medical Center, Cincinnati, OH

Cincinnati, Ohio, United States

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, United States

Dayton VA Medical Center, Dayton, OH

Dayton, Ohio, United States

Oklahoma City VA Medical Center, Oklahoma City, OK

Oklahoma City, Oklahoma, United States

Portland VA Medical Center, Portland, OR

Portland, Oregon, United States

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Pittsburgh, Pennsylvania, United States

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, United States

Memphis VA Medical Center, Memphis, TN

Memphis, Tennessee, United States

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Dallas, Texas, United States

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States

South Texas Health Care System, San Antonio, TX

San Antonio, Texas, United States

Canberra Hospital

Canberra, Australian Capital Territory, Australia

Liverpool Hospital

Liverpool, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

Austin Health

Heidelberg, Victoria, Australia

Penang Hospital

George Town, Pulau Pinang, Malaysia

Hospital Serdang

Sepang, Selangor, Malaysia

Auckland City Hospital

Auckland, Auckland, New Zealand

Taranaki Base Hospital

Westown, New Plymouth, New Zealand

Southern Arizona VA Health Care System, Tucson

Tucson, Arizona, United States

Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR

Little Rock, Arkansas, United States

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, United States

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, United States

Bay Pines VA Healthcare System, Pay Pines, FL

Bay Pines, Florida, United States

North Florida/South Georgia Veterans Health System, Gainesville, FL

Gainesville, Florida, United States

Charlie Norwood VA Medical Center, Augusta, GA

Augusta, Georgia, United States

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, United States

Jesse Brown VA Medical Center, Chicago, IL

Chicago, Illinois, United States

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Indianapolis, Indiana, United States

VA Boston Healthcare System West Roxbury Campus, West Roxbury, MA

West Roxbury, Massachusetts, United States

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, United States

New Mexico VA Health Care System, Albuquerque, NM

Albuquerque, New Mexico, United States

VA Salt Lake City Health Care System, Salt Lake City, UT

Salt Lake City, Utah, United States

Hunter Holmes McGuire VA Medical Center, Richmond, VA

Richmond, Virginia, United States

Salem VA Medical Center, Salem, VA

Salem, Virginia, United States

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, United States

Concord Hospital

Concord, New South Wales, Australia

Gosford Hospital

Gosford, New South Wales, Australia

Nepean Hospital

Kingswood, New South Wales, Australia

St. George Hospital

Kogarah, New South Wales, Australia

Northern Health

Epping, Victoria, Australia

Fremantle Hospital

Fremantle, Western Australia, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

University of Malaya Medical Center

Kuala Lumpur, Kuala Lumpur, Malaysia

Wellington Hospital

Newtown, Wellington Region, New Zealand

Countries

United States; Australia; Malaysia; New Zealand

References

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.

Reference Type: DERIVED

PMID: 29130810 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

1011387

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

578

Identifier Type: -

Identifier Source: org_study_id