Prevention of Serious Adverse Events Following Angiography

Phase 3

Completed

Conditions: Kidney Disease
Acute Renal Failure
Coronary Artery Disease

Interventions: Drug: IV isotonic saline
Drug: IV isotonic bicarbonate
Drug: Placebo
Drug: N-acetylcysteine

Registration Number: NCT01467466

Lead Sponsor: VA Office of Research and Development

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 5177

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

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Saline & oral N-acetylcysteine	IV isotonic saline	IV isotonic saline and oral N-acetylcysteine drug capsule
Bicarbonate & oral placebo	Placebo	IV isotonic bicarbonate and oral placebo drug capsule
Bicarbonate & oral N-acetylcysteine	IV isotonic bicarbonate	IV isotonic bicarbonate and oral N-acetylcysteine drug capsule
Saline & oral placebo	Placebo	IV isotonic saline and oral placebo drug capsule
Bicarbonate & oral placebo	IV isotonic bicarbonate	IV isotonic bicarbonate and oral placebo drug capsule
Saline & oral placebo	IV isotonic saline	IV isotonic saline and oral placebo drug capsule
Saline & oral N-acetylcysteine	N-acetylcysteine	IV isotonic saline and oral N-acetylcysteine drug capsule
Bicarbonate & oral N-acetylcysteine	N-acetylcysteine	IV isotonic bicarbonate and oral N-acetylcysteine drug capsule

Primary Outcome Measures

Name	Time	Method
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.	Within 90 days following angiography	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.
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.	Within 90 days following angiography	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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (54): Liverpool Hospital
🇦🇺
Liverpool, New South Wales, Australia
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
Atlanta VA Medical and Rehab Center, Decatur, GA
🇺🇸
Decatur, Georgia, United States
Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR
🇺🇸
Little Rock, Arkansas, United States
St. Louis VA Medical Center John Cochran Division, St. Louis, MO
🇺🇸
Saint Louis, Missouri, United States
Wellington Hospital
🇳🇿
Newtown, Wellington, New Zealand
Flinders Medical Centre
🇦🇺
Bedford Park, South Australia, Australia
Charlie Norwood VA Medical Center, Augusta, GA
🇺🇸
Augusta, Georgia, United States
Jesse Brown VA Medical Center, Chicago, IL
🇺🇸
Chicago, Illinois, United States
Auckland City Hospital
🇳🇿
Auckland, New Zealand
North Florida/South Georgia Veterans Health System, Gainesville, FL
🇺🇸
Gainesville, Florida, United States
VA Western New York Healthcare System, Buffalo, NY
🇺🇸
Buffalo, New York, United States
Hunter Holmes McGuire VA Medical Center, Richmond, VA
🇺🇸
Richmond, Virginia, United States
Penang Hospital
🇲🇾
George Town, Penang, Malaysia
Louis Stokes VA Medical Center, Cleveland, OH
🇺🇸
Cleveland, Ohio, United States
Fremantle Hospital
🇦🇺
Fremantle, Western Australia, Australia
Sir Charles Gairdner Hospital
🇦🇺
Nedlands, Western Australia, Australia
Royal Perth Hospital
🇦🇺
Perth, Western Australia, Australia
VA Palo Alto Health Care System, Palo Alto, CA
🇺🇸
Palo Alto, California, United States
Kansas City VA Medical Center, Kansas City, MO
🇺🇸
Kansas City, Missouri, United States
VA Boston Healthcare System West Roxbury Campus, West Roxbury, MA
🇺🇸
West Roxbury, Massachusetts, United States
New Mexico VA Health Care System, Albuquerque, NM
🇺🇸
Albuquerque, New Mexico, United States
Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
🇺🇸
New York, New York, United States
Concord Hospital
🇦🇺
Concord, New South Wales, Australia
Nepean Hospital
🇦🇺
Kingswood, New South Wales, Australia
Gosford Hospital
🇦🇺
Gosford, New South Wales, Australia
St. George Hospital
🇦🇺
Kogarah, New South Wales, Australia
Royal North Shore Hospital
🇦🇺
St. Leonards, New South Wales, Australia
Taranaki Base Hospital
🇳🇿
Westown, New Plymouth, New Zealand
San Francisco VA Medical Center, San Francisco, CA
🇺🇸
San Francisco, California, United States
Durham VA Medical Center, Durham, NC
🇺🇸
Durham, North Carolina, United States
South Texas Health Care System, San Antonio, TX
🇺🇸
San Antonio, Texas, United States
Richard L. Roudebush VA Medical Center, Indianapolis, IN
🇺🇸
Indianapolis, Indiana, United States
Minneapolis VA Health Care System, Minneapolis, MN
🇺🇸
Minneapolis, Minnesota, United States
VA Salt Lake City Health Care System, Salt Lake City, UT
🇺🇸
Salt Lake City, Utah, United States
Cincinnati VA Medical Center, Cincinnati, OH
🇺🇸
Cincinnati, Ohio, United States
Portland VA Medical Center, Portland, OR
🇺🇸
Portland, Oregon, United States
Oklahoma City VA Medical Center, Oklahoma City, OK
🇺🇸
Oklahoma City, Oklahoma, United States
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
🇺🇸
Pittsburgh, Pennsylvania, 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
Michael E. DeBakey VA Medical Center, Houston, TX
🇺🇸
Houston, Texas, 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
VA Ann Arbor Healthcare System, Ann Arbor, MI
🇺🇸
Ann Arbor, Michigan, United States
University of Malaya Medical Center
🇲🇾
Kuala Lumpur, Malaysia
Northern Health
🇦🇺
Epping, Victoria, Australia
Southern Arizona VA Health Care System, Tucson
🇺🇸
Tucson, Arizona, 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
Hospital Serdang
🇲🇾
Sepang, Selangor, Malaysia
Canberra Hospital
🇦🇺
Canberra, Australian Capital Territory, Australia
Austin Health
🇦🇺
Heidelberg, Victoria, Australia