Prevention of Serious Adverse Events Following Angiography

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Acute Renal Failure, Kidney Disease, Coronary Artery Disease

Intervention / Treatment
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* Drug: IV isotonic saline
* Drug: IV isotonic bicarbonate
* Drug: N-acetylcysteine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Saline & oral placebo<br>IV isotonic saline and oral placebo drug capsule | Drug: IV isotonic saline<br>* 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.<br>Drug: Placebo<br>* 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.<br>|
| Active Comparator: Saline & oral N-acetylcysteine<br>IV isotonic saline and oral N-acetylcysteine drug capsule | Drug: IV isotonic saline<br>* 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.<br>Drug: N-acetylcysteine<br>* 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.<br>* Other names: NAC;|
| Active Comparator: Bicarbonate & oral placebo<br>IV isotonic bicarbonate and oral placebo drug capsule | Drug: IV isotonic bicarbonate<br>* 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.<br>Drug: Placebo<br>* 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.<br>|
| Active Comparator: Bicarbonate & oral N-acetylcysteine<br>IV isotonic bicarbonate and oral N-acetylcysteine drug capsule | Drug: IV isotonic bicarbonate<br>* 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.<br>Drug: N-acetylcysteine<br>* 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.<br>* Other names: NAC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal, cardiovascular, kidney, heart, clinical trial, double-blind, multi-site trial, randomized, drug treatment, IV solutions, antioxidant