Prevention of Serious Adverse Events Following Angiography (PRESERVE)

VA Office of Research and Development

Status and phase: Completed; Phase 3

Conditions: Coronary Artery Disease; Acute Renal Failure; Kidney Disease

Treatments: Drug: Placebo; Drug: IV isotonic bicarbonate; Drug: IV isotonic saline; Drug: N-acetylcysteine

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT01467466

578

1011387 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 5,177 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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5,177 participants in 4 patient groups

Saline & oral placebo

Active Comparator group

Description:

IV isotonic saline and oral placebo drug capsule

Treatment:

Drug: IV isotonic saline

Drug: Placebo

Saline & oral N-acetylcysteine

Active Comparator group

Description:

IV isotonic saline and oral N-acetylcysteine drug capsule

Treatment:

Drug: N-acetylcysteine

Drug: IV isotonic saline

Bicarbonate & oral placebo

Active Comparator group

Description:

IV isotonic bicarbonate and oral placebo drug capsule

Treatment:

Drug: IV isotonic bicarbonate

Drug: Placebo

Bicarbonate & oral N-acetylcysteine

Active Comparator group

Description:

IV isotonic bicarbonate and oral N-acetylcysteine drug capsule

Treatment:

Drug: N-acetylcysteine

Drug: IV isotonic bicarbonate