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.

Study Timeline

• Study First Submitted: 2011-10-26
• Study First Submitted QC: 2011-11-03
• Study First Posted: 2011-11-08
• Study Start: 2013-10-07
• Primary Completion: 2017-09-29
• Study Completion: 2017-10-17
• Results First Submitted: 2018-10-02
• Results First Submitted QC: 2018-11-06
• Results First Posted: 2018-11-09
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-21
• Last Update Posted: 2022-10-03

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.

Trial Locations

Locations (54)

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

VA Palo Alto Health Care System, Palo Alto, CA; 🇺🇸 Palo Alto, California, 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

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